FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kawaguchi, KR Park, K Chinnaiyan, A Loda, M Robinson, BD Lis, R Scherr, DS Rosenberg, JE Rubin, MA Mosquera, JM AF Kawaguchi, K. R. Park, K. Chinnaiyan, A. Loda, M. Robinson, B. D. Lis, R. Scherr, D. S. Rosenberg, J. E. Rubin, M. A. Mosquera, J. M. TI Differential Expression of SPINK1 in Urothelial Neoplasia: Clinical and Pathological Implications SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol (USCAP) C1 Weill Cornell Med Coll, New York, NY USA. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 907 BP 217A EP 217A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901184 ER PT J AU Miyai, K Yamamoto, S Iwaya, K Matsubara, O Mark, EJ AF Miyai, K. Yamamoto, S. Iwaya, K. Matsubara, O. Mark, E. J. TI Consecutive Progression from Intratubular Germ Cell Neoplasm, Unclassified (IGCNU) to Seminoma and Ultimately to Embryonal Carcinoma of the Adult Testis: An Allelotyping Analysis of Cases with Embryonal Carcinoma Accompanied by Co-Existing Seminoma and/or IGCNU Components SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Natl Def Med Coll, Tokorozawa, Saitama 359, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 952 BP 228A EP 228A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901229 ER PT J AU Wirth, G Lu, J Wu, S Dahl, DM Olumi, AF McDougal, WS Young, RH Wu, CL AF Wirth, G. Lu, J. Wu, S. Dahl, D. M. Olumi, A. F. McDougal, W. S. Young, R. H. Wu, C-L TI Close Surgical Margins after Radical Prostatectomy Are an Independent Predictor of Prostate Cancer Recurrent SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 [Wirth, G.; Lu, J.; Wu, S.; Dahl, D. M.; Olumi, A. F.; McDougal, W. S.; Young, R. H.; Wu, C-L] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1061 BP 252A EP 252A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901338 ER PT J AU Bandyopadhyay, S Van de Vijver, KK Oliva, E Nucci, MR Shi, D Qureshi, F Hayek, K Alosh, B Feng, Z Jaratli, H Schultz, D Ali-Fehmi, R AF Bandyopadhyay, S. Van de Vijver, K. K. Oliva, E. Nucci, M. R. Shi, D. Qureshi, F. Hayek, K. Alosh, B. Feng, Z. Jaratli, H. Schultz, D. Ali-Fehmi, R. TI Tumor Size as a Prognostic Factor in Uterine Serous Carcinoma: A Large Multi-Institutional Study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Wayne State Univ, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Henry Ford Hlth Syst, Detroit, MI USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1090 BP 259A EP 259A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901367 ER PT J AU Chiang, S Castilla, MA Palacios, J Oliva, E AF Chiang, S. Castilla, M. A. Palacios, J. Oliva, E. TI microRNA Expression Profiling of Low-Grade Endometrial Stromal Sarcomas and Undifferentiated Endometrial Sarcomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol (USCAP) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Univ Virgen del Rocio, Inst Invest Biomed, Seville, Spain. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1106 BP 263A EP 263A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901383 ER PT J AU Chiang, S Van de Vijver, K Loureiro, J Nucci, M Oliva, E AF Chiang, S. Van de Vijver, K. Loureiro, J. Nucci, M. Oliva, E. TI Do Mitotic Index and Tumor Cell Necrosis Predict Patient Outcome in Low-Grade Endometrial Stromal Sarcomas? A Study of 33 Patients SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol (USCAP) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Maastricht Univ, Med Ctr, Maastricht, Netherlands. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1105 BP 263A EP 263A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901382 ER PT J AU DeLair, D Van de Vijver, K Park, KJ Oliva, E AF DeLair, D. Van de Vijver, K. Park, K. J. Oliva, E. TI Wolffian Tumors of the Female Genital Tract: A Study of 32 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol (USCAP) C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1114 BP 265A EP 265A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901391 ER PT J AU Ip, PP Irving, JA McCluggage, GW Young, RH AF Ip, P. P. Irving, J. A. McCluggage, G. W. Young, R. H. TI Papillary Proliferation of the Endometrium: A Clinicopathologic Study of 56 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Univ Hong Kong, Queen Mary Hosp, Hksar, Hong Kong, Peoples R China. Royal Jubilee Hosp, Victoria, BC, Canada. Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1163 BP 277A EP 278A PG 2 WC Pathology SC Pathology GA 888EP UT WOS:000299986901440 ER PT J AU Lee, CH Ali, R Marino-Enriquez, A Ou, WB Zhu, M Guo, X Brunner, AL Chiang, S Oliva, E Rouzbahman, M Gilks, CB Dal Cin, P West, PB van de Rijn, M Fletcher, JA Nucci, MR AF Lee, C-H Ali, R. Marino-Enriquez, A. Ou, W-B Zhu, M. Guo, X. Brunner, A. L. Chiang, S. Oliva, E. Rouzbahman, M. Gilks, C. B. Dal Cin, P. West, P. B. van de Rijn, M. Fletcher, J. A. Nucci, M. R. TI Cyclin D1 Is a Sensitive and Specific Diagnostic Immunomarker for YWHAE-FAM22A/B Endometrial Stromal Sarcoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Vancouver Gen Hosp, Vancouver, BC, Canada. Brigham & Womens Hosp, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Vancouver, MA USA. Toronto Gen Hosp, Toronto, ON, Canada. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1183 BP 282A EP 282A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901460 ER PT J AU Loureiro, J Borger, D Van de Vijver, K Dias-Santagata, D Penson, R Iafrate, J Oliva, E AF Loureiro, J. Borger, D. Van de Vijver, K. Dias-Santagata, D. Penson, R. Iafrate, J. Oliva, E. TI Utility of the SNaPshot Assay in Ovarian Carcinoma Genotyping SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 [Loureiro, J.; Borger, D.; Van de Vijver, K.; Dias-Santagata, D.; Penson, R.; Iafrate, J.; Oliva, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1191 BP 284A EP 284A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901468 ER PT J AU Soucy, G Wang, HH Farraye, FA Schmidt, JF Farris, AB Lauwers, GY Cerda, SR Dendrinos, KG Odze, RD AF Soucy, Genevieve Wang, Helen H. Farraye, Francis A. Schmidt, Jason F. Farris, Alton B. Lauwers, Gregory Y. Cerda, Sandra R. Dendrinos, Kleanthis G. Odze, Robert D. TI Clinical and pathological analysis of colonic Crohn's disease, including a subgroup with ulcerative colitis-like features SO MODERN PATHOLOGY LA English DT Article DE colitis; ileitis; inflammatory bowel disease; pathology; ulcerative colitis ID INFLAMMATORY-BOWEL-DISEASE; MONTREAL CLASSIFICATION; INDETERMINATE COLITIS; NOD2/CARD15 GENOTYPE; HEAL POUCH; FOLLOW-UP; ANASTOMOSIS; RECURRENCE; BEHAVIOR; SURGERY AB Little is known regarding the clinical and, in particular, pathological manifestations of patients with isolated colonic Crohn's disease. The purpose of this study was to evaluate the clinical and pathological features of patients with Crohn's disease limited to the colon at initial presentation, and to determine whether there are any histological features that are predictive of outcome after surgery. The clinical features, outcome after surgery, and pathological features of colonic resection specimens of 73 patients who presented initially with isolated colonic Crohn's disease were evaluated and compared with 45 Crohn's disease patients who presented initially with both ileal and colonic involvement. Clinically, patients with isolated colonic Crohn's disease presented at a significantly older age at the time of diagnosis, and had a significantly shorter duration of colitis before surgical resection, than did patients with ileocolonic Crohn's disease at disease onset. Pathologically, patients with isolated colonic Crohn's disease showed a significantly higher proportion of cases with subtotal, total, or left-sided colitis, and significantly fewer strictures/stenosis, pericolonic adhesions, pyloric metaplasia, and cases with proximal worse than distal colonic disease. Overall, patients with isolated colonic Crohn's disease showed a trend toward a lower number of major microscopic Crohn's disease features. A small proportion of patients from both Crohn's disease groups (14% and 13%, respectively) showed inflammatory disease limited to the mucosa, without mural involvement, reminiscent of ulcerative colitis, and these were termed 'ulcerative colitis-like Crohn's disease'. These patients were significantly younger than those with mural involvement. Overall, 44% of patients from both Crohn's disease groups developed at least one adverse outcome, and neither the number nor the type of major Crohn's disease features correlated with adverse outcome. Patients with isolated colonic involvement have distinctive clinical and pathological features. A small subgroup of Crohn's patients shows only mucosal involvement reminiscent of ulcerative colitis. Modern Pathology (2012) 25, 295-307; doi:10.1038/modpathol.2011.120; published online 12 August 2011 C1 [Odze, Robert D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Soucy, Genevieve] Univ Montreal, Dept Pathol, Ctr Hosp, Montreal, PQ H3C 3J7, Canada. [Wang, Helen H.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. [Farraye, Francis A.; Cerda, Sandra R.] Boston Med Ctr, Dept Gastroenterol, Boston, MA USA. [Schmidt, Jason F.] Methodist Hlth Syst, Dept Pathol, Dallas, TX USA. [Farris, Alton B.; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dendrinos, Kleanthis G.] Internal Med Grp, Dept Gastroenterol, Cheyenne, WY USA. RP Odze, RD (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM rodze@partners.org NR 44 TC 11 Z9 11 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 IS 2 BP 295 EP 307 DI 10.1038/modpathol.2011.120 PG 13 WC Pathology SC Pathology GA 888EK UT WOS:000299986400015 PM 21841769 ER PT J AU Van de Vijver, KK Liu, L Iafrate, AJ Oliva, E AF Van de Vijver, K. K. Liu, L. Iafrate, A. J. Oliva, E. TI Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Endometrium: Frequency and Clinicopathologic Correlation of 41 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 [Van de Vijver, K. K.; Liu, L.; Iafrate, A. J.; Oliva, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1254 BP 298A EP 299A PG 2 WC Pathology SC Pathology GA 888EP UT WOS:000299986901531 ER PT J AU Huck, AE Faquin, WC Stone, JH Nielsen, GP Deshpande, V AF Huck, A. E. Faquin, W. C. Stone, J. H. Nielsen, G. P. Deshpande, V. TI Fibrosing Variant of Hashimoto's Thyroiditis Is an IgG4 Related Disease SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1305 BP 310A EP 310A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901582 ER PT J AU Boyer, DF Attar, E Hasserjian, RP AF Boyer, D. F. Attar, E. Hasserjian, R. P. TI Fli-1 Expression Is Increased in Erythroblasts in MDS with Del(5q) and Correlates with Response to Lenalidomide SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 [Boyer, D. F.; Attar, E.; Hasserjian, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1366 BP 325A EP 326A PG 2 WC Pathology SC Pathology GA 888EP UT WOS:000299986901643 ER PT J AU Calvo, KR Wang, W Corrigan-Cummins, M Zingone, A Costello, R Korde, N Ghobrial, I Landgren, O AF Calvo, K. R. Wang, W. Corrigan-Cummins, M. Zingone, A. Costello, R. Korde, N. Ghobrial, I. Landgren, O. TI MicroRNA Profiles of the Bone Marrow Microenvironment and Serum in Multiple Myeloma Reveal Micrornas in the Serum Associated with Myeloma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol (USCAP) C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Calvo, Katherine/A-8109-2009 NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1369 BP 326A EP 326A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901646 ER PT J AU Carvajal-Cuenca, A Salaverria, I Royo, C Clot, G Navarro, A Hartmann, EM Trim, N Woroniecka, R Erber, W Gaulard, P Wlodarska, I Rymkiewicz, G Ott, G Rosenwald, A Lopez-Guillermo, A Quintanilla-Fend, L Ferry, JA Harris, NL Jaffe, ES Siebert, R Campo, E Bea, S AF Carvajal-Cuenca, A. Salaverria, I. Royo, C. Clot, G. Navarro, A. Hartmann, E. M. Trim, N. Woroniecka, R. Erber, W. Gaulard, P. Wlodarska, I. Rymkiewicz, G. Ott, G. Rosenwald, A. Lopez-Guillermo, A. Quintanilla-Fend, L. Ferry, J. A. Harris, N. L. Jaffe, E. S. Siebert, R. Campo, E. Bea, S. TI Clinicopathologic Characterization of Cyclin D1-Negative Mantle Cell Lymphoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Univ Barcelona, Hosp Clin, Barcelona, Spain. Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. Addenbrookes Hosp, Cambridge, England. MSCM Canc Ctr & Inst, Warsaw, Poland. Hop Henri Mondor, F-94010 Creteil, France. Catholic Univ Louvain, Ctr Human Genet, B-3000 Louvain, Belgium. Robert Bosch Krankenhaus, Stuttgart, Germany. Univ Tubingen, Inst Pathol, D-7400 Tubingen, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. Univ Kiel, Kiel, Germany. RI Navarro, Alba/H-2611-2015; Royo, Cristina/H-3193-2015 OI Navarro, Alba/0000-0002-4041-0974; Royo, Cristina/0000-0002-1214-4656 NR 0 TC 1 Z9 1 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1370 BP 326A EP 327A PG 2 WC Pathology SC Pathology GA 888EP UT WOS:000299986901647 ER PT J AU Chen, BJ Ouyang, J Sinha, P Shipp, MA Fletcher, CDM Rodig, SJ AF Chen, B. J. Ouyang, J. Sinha, P. Shipp, M. A. Fletcher, C. D. M. Rodig, S. J. TI Expression of Galectin-1 by EBV-Positive Lymphoproliferative Disorders SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1379 BP 329A EP 329A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901656 ER PT J AU Courville, E Wu, Y Kourda, J Brockmann, J de Leval, L Orazi, A Hasserjian, R AF Courville, E. Wu, Y. Kourda, J. Brockmann, J. de Leval, L. Orazi, A. Hasserjian, R. TI Acute Myeloid Leukemia Arising from Chronic Myelomonocytic Leukemia Has Poor Prognosis and High Incidence of Normal Karyotype and NPM1 Mutation SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Weill Cornell Med Coll, New York, NY USA. Inst Univ Pathol, Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1387 BP 331A EP 331A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901664 ER PT J AU Hwang, DG Dorfman, DM Briggs, DA Silverio, R Pozdnyakova, O AF Hwang, D. G. Dorfman, D. M. Briggs, D. A. Silverio, R. Pozdnyakova, O. TI Screening for Myelodysplastic Syndromes on Peripheral Blood Using the NEUT-X Parameter on the New Sysmex XE-5000 Analyzer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1436 BP 343A EP 343A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901713 ER PT J AU Kunder, CA Deangelo, DJ Gotlib, JR Gitana, G Atwater, SK George, TI AF Kunder, C. A. Deangelo, D. J. Gotlib, J. R. Gitana, G. Atwater, S. K. George, T. I. TI Loss of CD25 Expression in Advanced Systemic Mastocytosis Patients Treated with Midostaurin (PKC412) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Stanford Univ, Stanford, CA 94305 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1462 BP 349A EP 349A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901739 ER PT J AU Louissaint, A Ackerman, A Ferry, JA Iafrate, AJ Zukerberg, LR Harris, NL Hasserjian, RP AF Louissaint, A. Ackerman, A. Ferry, J. A. Iafrate, A. J. Zukerberg, L. R. Harris, N. L. Hasserjian, R. P. TI Pediatric-Type Follicular Lymphoma Occurs in Both Children and Adults and Is Characterized by a High Proliferation Index and the Absence of a BCL2 Gene Rearrangement SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 [Louissaint, A.; Ackerman, A.; Ferry, J. A.; Iafrate, A. J.; Zukerberg, L. R.; Harris, N. L.; Hasserjian, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1483 BP 353A EP 353A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901760 ER PT J AU Sohani, AR Mahindra, A Khosroshahi, A Stone, JH Deshpande, V Hasserjian, RP AF Sohani, A. R. Mahindra, A. Khosroshahi, A. Stone, J. H. Deshpande, V. Hasserjian, R. P. TI Bone Marrow Manifestations of IgG4-Related Disease SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 [Sohani, A. R.; Mahindra, A.; Khosroshahi, A.; Stone, J. H.; Deshpande, V.; Hasserjian, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1553 BP 370A EP 371A PG 2 WC Pathology SC Pathology GA 888EP UT WOS:000299986902065 ER PT J AU Song, JY Eberle, FC Xi, L Raffeld, M Harris, NL Wilson, WH Pittaluga, S Jaffe, ES AF Song, J. Y. Eberle, F. C. Xi, L. Raffeld, M. Harris, N. L. Wilson, W. H. Pittaluga, S. Jaffe, E. S. TI Nodal Involvement by Transformed Cutaneous CD30-Positive T-Cell Lymphoma Mimicking Classical Hodgkin Lymphoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1556 BP 372A EP 372A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902068 ER PT J AU Tan, KL Scott, DW Hong, F Horning, SJ Fisher, RI Bartlett, NL Shepherd, LE Connors, JM Kahl, BS Gordon, LI Steidl, C Gascoyne, RD AF Tan, K. L. Scott, D. W. Hong, F. Horning, S. J. Fisher, R. I. Bartlett, N. L. Shepherd, L. E. Connors, J. M. Kahl, B. S. Gordon, L. I. Steidl, C. Gascoyne, R. D. TI Tumor-Associated Macrophages Predict Inferior Outcomes in Locally Advanced and Advanced Stage Classical Hodgkin Lymphoma - A Correlative Study from the E2496 Intergroup Trial SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Genentech Inc, San Francisco, CA 94080 USA. Univ Rochester, Rochester, NY 14627 USA. Washington Univ, St Louis, MO 63130 USA. NCIC Clin Trials Off, Kingston, ON, Canada. Univ Wisconsin, Madison, WI 53706 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1568 BP 374A EP 375A PG 2 WC Pathology SC Pathology GA 888EP UT WOS:000299986902080 ER PT J AU McClintock, DS Bakst, JB Gilbertson, JR AF McClintock, D. S. Bakst, J. B. Gilbertson, J. R. TI Using Computerized Simulations To Measure the Effects of Full Adoption Whole Slide Imaging on Medium and High Volume Clinical Histology Laboratories SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1643 BP 393A EP 393A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902155 ER PT J AU Yagi, Y Bautista, PA AF Yagi, Y. Bautista, P. A. TI Whole Slide Imaging System Resolution Evaluation Slide Set Development: Toward Standardization SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 [Yagi, Y.; Bautista, P. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1650 BP 394A EP 395A PG 2 WC Pathology SC Pathology GA 888EP UT WOS:000299986902162 ER PT J AU Olar, A Stein, TD Davidson, CJ Perry, A Gheorghe, G AF Olar, A. Stein, T. D. Davidson, C. J. Perry, A. Gheorghe, G. TI Central Nervous System Involvement by Myeloid Sarcoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Methodist Hosp, Houston, TX 77030 USA. Boston Univ, Sch Med, Boston VA Med Ctr, Jamaica Plain, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Med Coll Wisconsin, Childrens Hosp Wisconsin, Milwaukee, WI 53226 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1808 BP 434A EP 434A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902320 ER PT J AU Sioletic, S Alexander, B Lauriola, L Balducci, M Ligon, K AF Sioletic, S. Alexander, B. Lauriola, L. Balducci, M. Ligon, K. TI Evaluation of Interactions of PI3K Pathway, IDH1(R132H), and OLIG2 Expression in Newly Diagnosed Glioblastoma Clinical Outcomes SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Gemelli Hosp, Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1820 BP 436A EP 436A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902332 ER PT J AU Boyer, DF Yang, Y Wright, CVE AF Boyer, D. F. Yang, Y. Wright, C. V. E. TI Multipotent Progenitor Cells in Mouse Fetal Pancreas Are Defined by High Sox9 and Low Ngn3 SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1841 BP 441A EP 441A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902353 ER PT J AU Khor, TS Le, LP Iafrate, AJ Lauwers, GY Deshpande, V AF Khor, T. S. Le, L. P. Iafrate, A. J. Lauwers, G. Y. Deshpande, V. TI Are Pancreatic Endocrine Neoplasms in Tuberous Sclerosis Complex a Syndrome Associated Lesion? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 [Khor, T. S.; Le, L. P.; Iafrate, A. J.; Lauwers, G. Y.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1856 BP 445A EP 445A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902368 ER PT J AU Lew, M Morales-Oyarvide, V Liao, X Ogino, S Chen, JH Pitman, MB Mino-Kenudson, M AF Lew, M. Morales-Oyarvide, V. Liao, X. Ogino, S. Chen, J-H Pitman, M. B. Mino-Kenudson, M. TI Clinicopathologic Characteristics and Biologic Behavior of Concurrent Pancreatic Ductal Adenocarcinoma (PDAC) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol (USCAP) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Indiana Univ, Indianapolis, IN 46204 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1861 BP 446A EP 446A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902373 ER PT J AU Lew, M Hong, T Deshpande, V AF Lew, M. Hong, T. Deshpande, V. TI Comparison of Histologic Grading Schemes for Response to Neoadjuvant Therapy in Pancreatic Adenocarcinoma (PDAC) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol (USCAP) C1 [Lew, M.; Hong, T.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1862 BP 446A EP 446A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902374 ER PT J AU Xiao, HD Pitman, MB Mino-Kenudson, M AF Xiao, H. D. Pitman, M. B. Mino-Kenudson, M. TI Downregulation of PTEN Expression in Intraductal Papillary Mucinous Neoplasm of the Pancreas Is Associated with an Invasive Phenotype SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 [Xiao, H. D.; Pitman, M. B.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1876 BP 449A EP 450A PG 2 WC Pathology SC Pathology GA 888EP UT WOS:000299986902388 ER PT J AU Kerr, SE Schnabel, CA Sullivan, PS Zhang, Y Singh, V Carey, B Erlander, MG Highsmith, WE Dry, SM Brachtel, EF AF Kerr, S. E. Schnabel, C. A. Sullivan, P. S. Zhang, Y. Singh, V. Carey, B. Erlander, M. G. Highsmith, W. E. Dry, S. M. Brachtel, E. F. TI Multisite Analytical Validation of a 92-Gene Molecular Classifier for Cancers of Uncertain Primary SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Mayo Clin, Rochester, MN USA. BioTheranostics Inc, San Diego, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1888 BP 453A EP 453A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902400 ER PT J AU Bauer, D Mitchell, C Straight, K Lathan, C Stelow, E Luer, S Muhammed, S Evans, A Sholl, L Rosai, J Giraldi, E Oakley, R Rodriguez-Galindo, C London, W Sallan, S Bradner, J French, C AF Bauer, D. Mitchell, C. Straight, K. Lathan, C. Stelow, E. Luer, S. Muhammed, S. Evans, A. Sholl, L. Rosai, J. Giraldi, E. Oakley, R. Rodriguez-Galindo, C. London, W. Sallan, S. Bradner, J. French, C. TI Clinicopathologic Features and Long-Term Outcomes of NUT Midline Carcinoma: An Index Report of the International NMC Registry SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Div Hematol Oncol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Dana Farber Harvard Canc Care, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Univ Virginia, Charlottesville, VA USA. Univ Childrens Hosp Bern, Inselspital, Bern, Switzerland. Italiano Int Ctr Oncol Pathol Consultat, Ctr Diagnost, Milan, Italy. Osped Riuniti Bergamo, I-24100 Bergamo, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 1964 BP 472A EP 472A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902476 ER PT J AU Kovach, AE Klepeis, V Mark, EJ Dias-Santagata, D Iafrate, AJ Mino-Kenudson, M AF Kovach, A. E. Klepeis, V. Mark, E. J. Dias-Santagata, D. Iafrate, A. J. Mino-Kenudson, M. TI C-Kit Expression Is Associated with KRAS Mutation in Lung Adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 [Kovach, A. E.; Klepeis, V.; Mark, E. J.; Dias-Santagata, D.; Iafrate, A. J.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 2002 BP 480A EP 480A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902514 ER PT J AU Matsubara, O Miyai, K Kikuchi, R Iwaya, K Nakatani, Y Mark, EJ AF Matsubara, O. Miyai, K. Kikuchi, R. Iwaya, K. Nakatani, Y. Mark, E. J. TI Acute Exacerbations of Interstitial Pneumonias in Amyopathic Dermatomyositis: Different Pathogenesis in Ordinary Dermatomyositis/Polymyositis When Compared to Amyopathic Dermatomyositis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Natl Def Med Coll, Tokorozawa, Saitama 359, Japan. Chiba Univ, Chiba, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 2014 BP 483A EP 483A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902526 ER PT J AU Nishino, M Klepeis, VE Yeap, B Bergethon, K Mark, MJ Lafrate, AJ Mino-Kenudson, M AF Nishino, M. Klepeis, V. E. Yeap, B. Bergethon, K. Mark, M. J. Lafrate, A. J. Mino-Kenudson, M. TI Histologic Multivariate Model for Predicting Presence of ALK-Rearrangement in Lung Adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 [Nishino, M.; Klepeis, V. E.; Yeap, B.; Bergethon, K.; Mark, M. J.; Lafrate, A. J.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 2021 BP 485A EP 485A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902533 ER PT J AU Rekhtman, N Paik, PK Arcila, ME Tafe, LJ Oxnard, GR Moreira, AL William, TD Zakowski, MF Mark, KG Ladanyi, M AF Rekhtman, N. Paik, P. K. Arcila, M. E. Tafe, L. J. Oxnard, G. R. Moreira, A. L. William, T. D. Zakowski, M. F. Mark, K. G. Ladanyi, M. TI Resolving the Controversy on EGFR/KRAS Mutations in Pulmonary Squamous Cell Carcinoma Via Comprehensive Pathologic Assessment Incorporating Immunohistochemistry SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 2032 BP 487A EP 487A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902544 ER PT J AU Shen, J Taneja, K Zhang, W Dillon, DA Gandhi, L Sholl, LM AF Shen, J. Taneja, K. Zhang, W. Dillon, D. A. Gandhi, L. Sholl, L. M. TI HER2 Mutated Lung Adenocarcinoma Is a Distinct Molecular and Clinicopathologic Entity SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Charlton Mem Hosp, Fall River, MA USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 2044 BP 490A EP 490A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902556 ER PT J AU Sholl, LM Iafrate, AJ Wu, MT Ligon, A Janne, PA Christiani, DC Loda, M Chirieac, LR AF Sholl, L. M. Iafrate, A. J. Wu, M-T Ligon, A. Janne, P. A. Christiani, D. C. Loda, M. Chirieac, L. R. TI Met Activation Is Associated with Unique Clinicopathologic and Molecular Features in Lung Adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Kaohsiung Med Univ, Kaohsiung, Taiwan. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 2046 BP 491A EP 491A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902558 ER PT J AU Travis, WD Rekhtman, N Shen, R Yi, ES Aubry, MC Cheney, R Dacic, S Flieder, D Funkhouser, W Illei, P Myers, J Tsao, MS Wilkerson, M Hammerman, P Govindan, R Hayes, N Meyerson, M AF Travis, W. D. Rekhtman, N. Shen, R. Yi, E. S. Aubry, M. C. Cheney, R. Dacic, S. Flieder, D. Funkhouser, W. Illei, P. Myers, J. Tsao, M. S. Wilkerson, M. Hammerman, P. Govindan, R. Hayes, N. Meyerson, M. TI Molecular Histologic Correlations in the Cancer Genome Atlas (TCGA) Study of Lung Squamous Cell Carcinoma (SQC) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 101st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 17-23, 2012 CL Vancouver, CANADA SP US & Canadian Acad Pathol C1 Mem Sloan Kettering, New York, NY USA. Mayo Clin, Rochester, MN USA. Univ Pittsburgh, Pittsburgh, PA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ N Carolina, Chapel Hill, NC USA. Johns Hopkins, Baltimore, MD USA. Penrose St Francis Hlth Serv, Colorado Springs, CO USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2012 VL 25 SU 2 MA 2049 BP 491A EP 491A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902561 ER PT J AU Patel, SJ Milwid, JM King, KR Bohr, S Iracheta-Velle, A Li, M Vitalo, A Parekkadan, B Jindal, R Yarmush, ML AF Patel, Suraj J. Milwid, Jack M. King, Kevin R. Bohr, Stefan Iracheta-Velle, Arvin Li, Matthew Vitalo, Antonia Parekkadan, Biju Jindal, Rohit Yarmush, Martin L. TI Gap junction inhibition prevents drug-induced liver toxicity and fulminant hepatic failure SO NATURE BIOTECHNOLOGY LA English DT Article ID ACETAMINOPHEN HEPATOTOXICITY; SURVEILLANCE; MECHANISMS AB Drug-induced liver injury (DILI) limits the development and application of many therapeutic compounds and presents major challenges to the pharmaceutical industry and clinical medicine(1,2). Acetaminophen-containing compounds are among the most frequently prescribed drugs and are also the most common cause of DILI3. Here we describe a pharmacological strategy that targets gap junction communication to prevent amplification of fulminant hepatic failure and acetaminophen-induced hepatotoxicity. We demonstrate that connexin 32 (Cx32), a key hepatic gap junction protein, is an essential mediator of DILI by showing that mice deficient in Cx32 are protected against liver damage, acute inflammation and death caused by liver-toxic drugs. We identify a small-molecule inhibitor of Cx32 that protects against liver failure and death in wild-type mice when co-administered with known hepatotoxic drugs. These findings indicate that gap junction inhibition could provide a pharmaceutical strategy to limit DILI and improve drug safety. C1 [Patel, Suraj J.; Milwid, Jack M.; King, Kevin R.; Bohr, Stefan; Iracheta-Velle, Arvin; Li, Matthew; Vitalo, Antonia; Parekkadan, Biju; Jindal, Rohit; Yarmush, Martin L.] Massachusetts Gen Hosp, Dept Surg, Ctr Engn Med, Boston, MA 02114 USA. [Patel, Suraj J.; Milwid, Jack M.; King, Kevin R.; Bohr, Stefan; Iracheta-Velle, Arvin; Li, Matthew; Vitalo, Antonia; Parekkadan, Biju; Jindal, Rohit; Yarmush, Martin L.] Shriners Burns Hosp, Boston, MA USA. [Patel, Suraj J.; Milwid, Jack M.; Yarmush, Martin L.] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, MIT, Cambridge, MA 02138 USA. [Jindal, Rohit; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Engn Med, Boston, MA 02114 USA. EM ireis@sbi.org OI Iracheta-Vellve, Arvin/0000-0002-6635-3904 FU Department of Defense; Shriners Hospitals for Children; US National Institutes of Health [DK059766, P41 EB-002503] FX The authors thank K. Willecke (University of Bonn) and D. Paul (Harvard University) for the generous gift of Cx32-/- mice, K. Willecke (University of Bonn) for connexin expressing HeLa cells, H. Duffy (Harvard Medical School) for development of the tissue scrape-and-load assay, and M. Izamis (Harvard Medical School) for high-performance liquid chromatography assistance. S.J.P. was supported in part by a Department of Defense Congressionally Directed Medical Research Program Prostate Cancer Predoctoral Training Award and a Shriners Hospitals for Children Postdoctoral Fellowship Award. The work was supported by grants from the US National Institutes of Health (DK059766 and P41 EB-002503) and from the Shriners Hospitals for Children. NR 27 TC 54 Z9 59 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD FEB PY 2012 VL 30 IS 2 BP 179 EP 183 DI 10.1038/nbt.2089 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 892EI UT WOS:000300269100021 PM 22252509 ER PT J AU Ahfeldt, T Schinzel, RT Lee, YK Hendrickson, D Kaplan, A Lum, DH Camahort, R Xia, F Shay, J Rhee, EP Clish, CB Deo, RC Shen, T Lau, FH Cowley, A Mowrer, G Al-Siddiqi, H Nahrendorf, M Musunuru, K Gerszten, RE Rinn, JL Cowan, CA AF Ahfeldt, Tim Schinzel, Robert T. Lee, Youn-Kyoung Hendrickson, David Kaplan, Adam Lum, David H. Camahort, Raymond Xia, Fang Shay, Jennifer Rhee, Eugene P. Clish, Clary B. Deo, Rahul C. Shen, Tony Lau, Frank H. Cowley, Alicia Mowrer, Greg Al-Siddiqi, Heba Nahrendorf, Matthias Musunuru, Kiran Gerszten, Robert E. Rinn, John L. Cowan, Chad A. TI Programming human pluripotent stem cells into white and brown adipocytes SO NATURE CELL BIOLOGY LA English DT Article ID LARGE GENE LISTS; ADIPOSE-TISSUE; ADULT HUMANS; PPAR-GAMMA; TRANSCRIPTIONAL CONTROL; ADAPTIVE THERMOGENESIS; STROMAL CELLS; DIFFERENTIATION; DERIVATION; IDENTIFICATION AB The utility of human pluripotent stem cells is dependent on efficient differentiation protocols that convert these cells into relevant adult cell types. Here we report the robust and efficient differentiation of human pluripotent stem cells into white or brown adipocytes. We found that inducible expression of PPARG2 alone or combined with CEBPB and/or PRDM16 in mesenchymal progenitor cells derived from pluripotent stem cells programmed their development towards a white or brown adipocyte cell fate with efficiencies of 85%-90%. These adipocytes retained their identity independent of transgene expression, could be maintained in culture for several weeks, expressed mature markers and had mature functional properties such as lipid catabolism and insulin-responsiveness. When transplanted into mice, the programmed cells gave rise to ectopic fat pads with the morphological and functional characteristics of white or brown adipose tissue. These results indicate that the cells could be used to faithfully model human disease. C1 [Ahfeldt, Tim; Schinzel, Robert T.; Lee, Youn-Kyoung; Hendrickson, David; Kaplan, Adam; Camahort, Raymond; Xia, Fang; Shay, Jennifer; Shen, Tony; Cowley, Alicia; Al-Siddiqi, Heba; Musunuru, Kiran; Rinn, John L.; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Ahfeldt, Tim; Schinzel, Robert T.; Lee, Youn-Kyoung; Kaplan, Adam; Camahort, Raymond; Xia, Fang; Shay, Jennifer; Shen, Tony; Lau, Frank H.; Cowley, Alicia; Mowrer, Greg; Al-Siddiqi, Heba; Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Ahfeldt, Tim; Schinzel, Robert T.; Lee, Youn-Kyoung; Kaplan, Adam; Camahort, Raymond; Xia, Fang; Shay, Jennifer; Rhee, Eugene P.; Lau, Frank H.; Mowrer, Greg; Al-Siddiqi, Heba; Gerszten, Robert E.; Cowan, Chad A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Schinzel, Robert T.] Free Univ Berlin, Fachbereich Biol, Inst Biol Mikrobiol, D-14195 Berlin, Germany. [Hendrickson, David; Rhee, Eugene P.; Clish, Clary B.; Musunuru, Kiran; Gerszten, Robert E.; Rinn, John L.; Cowan, Chad A.] 7 Cambridge Ctr, Broad Inst, Cambridge, MA 02142 USA. [Lum, David H.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Lum, David H.] Univ Utah, Dept Oncol Sci, Salt Lake City, UT 84112 USA. [Deo, Rahul C.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Deo, Rahul C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Deo, Rahul C.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Al-Siddiqi, Heba] Qatar Fdn, Div Res, Doha, Qatar. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Musunuru, Kiran] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Cowan, CA (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM ccowan@fas.harvard.edu RI Ahfeldt, Tim/E-2935-2017; OI Shen, Tony/0000-0002-7740-6389 FU Roberto and Allison Mignone Fund for Stem Cell Research; Harvard Stem Cell Institute, Hoffman-La Roche; Stowers Medical Institute FX The authors would like to thank T. Holm, A. Foudi and E. Hanson for critical reading, insight and suggestions; M. Henderson, J. Horn, K. Horn, I. Pomerantseva, A. Tseng and K. Kulig for their technical help; L. Prickett-Rice and K. Folz-Donahue of the HSCI-CRM Flow Cytometry Core Facility; D. Lieber and V. Mootha for assistance with cellular bioenergetic measurements; and J. Truelove and R. Weissleder for assistance with PET-CT imaging. T. Ahfeldt was supported by the Roberto and Allison Mignone Fund for Stem Cell Research. This work was financially sponsored in part by the Harvard Stem Cell Institute, Hoffman-La Roche and the Stowers Medical Institute. NR 47 TC 72 Z9 80 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD FEB PY 2012 VL 14 IS 2 BP 209 EP 219 DI 10.1038/ncb2411 PG 11 WC Cell Biology SC Cell Biology GA 893CF UT WOS:000300332500016 PM 22246346 ER PT J AU Schwamm, LH AF Schwamm, Lee H. TI STROKE IN 2011 Major advances across the spectrum of stroke care SO NATURE REVIEWS NEUROLOGY LA English DT Editorial Material ID INTRACRANIAL ARTERIAL-STENOSIS; ATRIAL-FIBRILLATION; WARFARIN; THERAPY; TRIAL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol ACC 720, Boston, MA 02114 USA. RP Schwamm, LH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol ACC 720, 55 Fruit St, Boston, MA 02114 USA. EM lschwamm@partners.org OI Schwamm, Lee/0000-0003-0592-9145 NR 10 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD FEB PY 2012 VL 8 IS 2 BP 63 EP 64 DI 10.1038/nrneurol.2011.225 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 894CE UT WOS:000300403800001 PM 22231192 ER PT J AU Klein, C Krainc, D AF Klein, Christine Krainc, Dimitri TI MOVEMENT DISORDERS IN 2011 Translating new research findings into clinical practice SO NATURE REVIEWS NEUROLOGY LA English DT Editorial Material ID PARKINSON-DISEASE; VPS35 C1 [Klein, Christine] Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Krainc, Dimitri] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Klein, C (reprint author), Univ Lubeck, Dept Neurol, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM christine.klein@neuro.uni-luebeck.de NR 9 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD FEB PY 2012 VL 8 IS 2 BP 65 EP 66 DI 10.1038/nrneurol.2011.212 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 894CE UT WOS:000300403800002 PM 22187001 ER PT J AU Wakimoto, H Mohapatra, G Kanai, R Curry, WT Yip, S Nitta, M Patel, AP Barnard, ZR Stemmer-Rachamimov, AO Louis, DN Martuza, RL Rabkin, SD AF Wakimoto, Hiroaki Mohapatra, Gayatry Kanai, Ryuichi Curry, William T., Jr. Yip, Stephen Nitta, Mai Patel, Anoop P. Barnard, Zachary R. Stemmer-Rachamimov, Anat O. Louis, David N. Martuza, Robert L. Rabkin, Samuel D. TI Maintenance of primary tumor phenotype and genotype in glioblastoma stem cells SO NEURO-ONCOLOGY LA English DT Article DE genomic profile; glioblastoma; glioblastoma stem cells; invasion; phenotype ID ADJUVANT TEMOZOLOMIDE; MALIGNANT GLIOMAS; GENETIC DIVERSITY; INITIATING CELLS; IN-VIVO; CANCER; PROGRESSION; EXPRESSION; EVOLUTION; PROFILES AB The clinicopathological heterogeneity of glioblastoma (GBM) and the various genetic and phenotypic subtypes in GBM stem cells (GSCs) are well described. However, the relationship between GSCs and the corresponding primary tumor from which they were isolated is poorly understood. We have established GSC-enriched neurosphere cultures from 15 newly diagnosed GBM specimens and examined the relationship between the histopathological and genomic features of GSC-derived orthotopic xenografts and those of the respective patient tumors. GSC-initiated xenografts recapitulate the distinctive cytological hallmarks and diverse histological variants associated with the corresponding patient GBM, including giant cell and gemistocytic GBM, and primitive neuroectodermal tumor (PNET)like components. This indicates that GSCs generate tumors that preserve patient-specific disease phenotypes. The majority of GSC-derived intracerebral xenografts (11 of 15) demonstrated a highly invasive behavior crossing the midline, whereas the remainder formed discrete nodular and vascular masses. In some cases, GSC invasiveness correlated with preoperative MRI, but not with the status of PI3-kinase/Akt pathways or O-6-methylguanine methyltransferase expression. Genome-wide screening by array comparative genomic hybridization and fluorescence in situ hybridization revealed that GSCs harbor unique genetic copy number aberrations. GSCs acquiring amplifications of the myc family genes represent only a minority of tumor cells within the original patient tumors. Thus, GSCs are a genetically distinct subpopulation of neoplastic cells within a GBM. These studies highlight the value of GSCs for preclinical modeling of clinically relevant, patient-specific GBM and, thus, pave the way for testing novel anti-GSC/GBM agents for personalized therapy. C1 [Wakimoto, Hiroaki; Kanai, Ryuichi; Curry, William T., Jr.; Patel, Anoop P.; Barnard, Zachary R.; Martuza, Robert L.; Rabkin, Samuel D.] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, Boston, MA 02114 USA. [Mohapatra, Gayatry; Nitta, Mai; Stemmer-Rachamimov, Anat O.; Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Louis, David N.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Wakimoto, Hiroaki; Mohapatra, Gayatry; Kanai, Ryuichi; Curry, William T., Jr.; Stemmer-Rachamimov, Anat O.; Louis, David N.; Martuza, Robert L.; Rabkin, Samuel D.] Harvard Univ, Sch Med, Boston, MA USA. [Yip, Stephen] BC Canc Agcy, Vancouver, BC, Canada. RP Wakimoto, H (reprint author), Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, 185 Cambridge St,CPZN 3800, Boston, MA 02114 USA. EM hwakimoto@partners.org RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU National Institute of Health [R01NS032677, R21NS067541, R01CA57683, P01NS024279]; Department of Defense [W81XWH-07-1-0359] FX This work was supported by the National Institute of Health (R01NS032677 to R. L. M., R21NS067541 to H. W., R01CA57683 to D.N.L., and P01NS024279 to A.O.S.) and the Department of Defense (W81XWH-07-1-0359 to S.D.R.). NR 47 TC 57 Z9 57 U1 1 U2 6 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 FEB PY 2012 VL 14 IS 2 BP 132 EP 144 DI 10.1093/neuonc/nor195 PG 13 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 892QO UT WOS:000300300900002 PM 22067563 ER PT J AU Baldwin, KJ Zivkovic, SA Lieberman, FS AF Baldwin, Kelly Jo Zivkovic, Sasa A. Lieberman, Frank S. TI Neurologic Emergencies in Patients Who Have Cancer: Diagnosis and Management SO NEUROLOGIC CLINICS LA English DT Article DE Leptomeningeal carcinomatosis; Cerebral edema; Seizure; Metastasis; Compressive myelopathy; Hydrocephalus; Stroke; Paraneoplastic ID SPINAL-CORD COMPRESSION; NONCONVULSIVE STATUS EPILEPTICUS; CLINICAL-PRACTICE GUIDELINE; PARANEOPLASTIC LIMBIC ENCEPHALITIS; NMDA-RECEPTOR ENCEPHALITIS; DURAL SINUS THROMBOSIS; NERVOUS-SYSTEM INFECTIONS; BRAIN METASTASES; EPIDURAL METASTASIS; CEREBROVASCULAR COMPLICATIONS AB The nervous system can be significantly affected by cancer. Neurologic symptoms are present in 30% to 50% of oncologic patients presenting to the emergency department or in neurologic consultation at teaching hospitals. Evaluation and treatment require collaborative effort between specialties. The causes of neurologic emergencies in patients with cancer are mostly related to effects of cancer, toxicities of treatments, infections, and paraneoplastic syndromes. These complications cause significant morbidity and mortality and require prompt and accurate diagnostic and treatment measures. This article reviews the common neurologic emergencies affecting patients with cancer and discusses epidemiology, clinical presentation, diagnosis, and treatment modalities. C1 [Zivkovic, Sasa A.] Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, Dept Neurol,MSSL Neurol, Pittsburgh, PA 15240 USA. [Baldwin, Kelly Jo] Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA 15213 USA. [Lieberman, Frank S.] Univ Pittsburgh, Med Ctr, Pittsburgh Canc Inst, Adult Neurooncol Program,Dept Neurol, Pittsburgh, PA 15232 USA. RP Zivkovic, SA (reprint author), Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, Dept Neurol,MSSL Neurol, Univ Dr C,10E Room 133, Pittsburgh, PA 15240 USA. EM zivksx@upmc.edu NR 119 TC 3 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD FEB PY 2012 VL 30 IS 1 BP 101 EP + DI 10.1016/j.ncl.2011.09.004 PG 29 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 894ZC UT WOS:000300465000007 PM 22284057 ER PT J AU Cunningham, ET Pasadhika, S Suhler, EB Zierhut, M AF Cunningham, Emmett T., Jr. Pasadhika, Sirichai Suhler, Eric B. Zierhut, Manfred TI Drug-induced Inflammation in Patients on TNF alpha Inhibitors SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Editorial Material DE drug-induced uveitis; sarcoidosis; granulomatous; inflixamab; etanercept; adalimumab ID OF-THE-LITERATURE; UVEITIS-LIKE SYNDROME; IRIS TRANSILLUMINATION; ORAL MOXIFLOXACIN; IFN-ALPHA; THERAPY; SARCOIDOSIS; DISEASE; DISORDERS; FUTURE C1 [Cunningham, Emmett T., Jr.] Calif Pacific Med Ctr, San Francisco, CA USA. [Cunningham, Emmett T., Jr.] Stanford Univ, Sch Med, Dept Ophthalmol, Stanford, CA 94305 USA. [Pasadhika, Sirichai] Univ Arizona, Coll Med, Dept Ophthalmol & Vis Sci, Tucson, AZ USA. [Suhler, Eric B.] Portland VA Med Ctr, Dept Ophthalmol, Portland, OR USA. [Suhler, Eric B.] Oregon Hlth & Sci Univ, Casey Eye Inst, Uveitis Div, Portland, OR 97201 USA. [Zierhut, Manfred] Univ Tubingen, Ctr Ophthalmol, Tubingen, Germany. RP Cunningham, ET (reprint author), W Coast Retina Med Grp, 185 Berry St,Lobby 2,Suite 130, San Francisco, CA 94107 USA. EM emmett_cunningham@yahoo.com NR 47 TC 3 Z9 3 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD FEB PY 2012 VL 20 IS 1 BP 2 EP 5 DI 10.3109/09273948.2011.644383 PG 4 WC Ophthalmology SC Ophthalmology GA 892AO UT WOS:000300259000002 PM 22324894 ER PT J AU Lee, JH Kirkham, JC McCormack, MC Medina, MA Nicholls, AM Randolph, MA Austen, WG AF Lee, Jeffrey H. Kirkham, John C. McCormack, Michael C. Medina, Miguel A. Nicholls, Alexa M. Randolph, Mark A. Austen, William G., Jr. TI A Novel Approach to Adipocyte Analysis SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ADIPOSE CELL SIZE; FAT-GRAFTS; TISSUE; OBESITY; MODEL AB Background: Fat grafting bench research is difficult because many traditional endpoints cannot be used reliably with adipocytes. Manual cell counting with trypan blue is a common method of measuring cell viability. There are, however, multiple known limitations, including human error, inability to analyze cell size, overestimation of adipocyte viability, and labor intensity. In this study, the authors demonstrate the effectiveness of an improved method of accurate adipocyte analysis using an automated cell counter. Methods: Human lipoaspirate was obtained, centrifuged, and digested. Samples were analyzed using a hemocytometer and an automated cell counter with two viability dyes. Results were then optimized by novel methods of preparation using carboxymethyl cellulose and formalin. Results: Manual trypan blue cell counts ranged from 2,750,000 to 19,200,000 live cells/ml. Automated cell counts significantly reduced variability (3,230,000 to 4,290,000 cells/ml). Counting cells between 40 and 150 mu m, which is more specific to adipocytes, yielded 1,040,000 to 1,420,000 viable cells/ml. Using a second viability dye, CellTiter Blue, cell counts ranged between 993,000 and 1,340,000 live cells/ml. Adding carboxymethyl cellulose substantially decreased sampling variability by 80 percent, and the use of formalin prevented the decrease in cell counts over 4 hours from 432,000 to 7,000 cells/ml. Conclusions: This novel method utilizing automated cell counters can more accurately identify the viable adipocyte population without the limitations of traditional cell counting. In addition, the use of carboxymethyl cellulose and formalin in the preparation process can decrease variability and stabilize cell counts over time. This is an efficient, specific, and reliable method of adipocyte analysis. (Plast. Reconstr. Surg. 129: 380, 2012.) C1 [Austen, William G., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Austen, WG (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St,WAC 435, Boston, MA 02114 USA. EM wausten@partners.org NR 23 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 2012 VL 129 IS 2 BP 380 EP 387 DI 10.1097/PRS.0b013e31823aea29 PG 8 WC Surgery SC Surgery GA 891TR UT WOS:000300240000072 PM 22286421 ER PT J AU Barone, AAL Zhou, ZY Hughes, MW Park, R Schulman, RM Lee, S Vidar, EN Shiba, TL Weber, EL Cetrulo, CL AF Barone, Angelo A. Leto Zhou, Zhao Y. Hughes, Michael W. Park, Ryan Schulman, Ruth M. Lee, Steven Vidar, Evan N. Shiba, Travis L. Weber, Erin L. Cetrulo, Curtis L., Jr. TI Lentiviral Transduction of Face and Limb Flaps: Implications for Immunomodulation of Vascularized Composite Allografts SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID MICROVASCULAR FREE FLAPS; GENE DELIVERY; RETROVIRAL VECTORS; VIVO TRANSDUCTION; THERAPY; KERATINOCYTES; TRANSPLANTS; EXPRESSION; TOLERANCE; EFFICIENT AB Background: Ex vivo introduction of an immunomodulatory transgene into a face or hand allograft may improve the risk-to-benefit ratio of vascularized composite allografts. Abrogation of the immunogenicity of the skin component of a face or hand allograft may decrease alloreactivity and permit the induction of immunologic tolerance. Proof-of-principle demonstrations of transduction of composite tissue have been established using adenoviral vectors, producing transient gene expression. The authors hypothesized that transduction, integration, and long-term expression of transgenes in a vascularized composite allograft could be achieved using lentiviral vectors. Methods: Ex vivo transduction of heterogeneous primary rat cell lines representative of a composite tissue flap's cellular architecture was performed using a luc-enhanced green fluorescent protein (eGFP) human immunodeficiency virus-1-based lentiviral vector. Ex vivo injections of rat superficial inferior epigastric artery flaps with the viral vector were performed intraarterially, intramuscularly, and intradermally. Results: Quantifiable reporter expression by flow cytometry (fluorescence-activated cell sorting) analysis and in vitro bioluminescence was observed. The luc-eGFP vector exhibited broad tropism and allowed transgene expression in relevant cell lines and throughout the flaps. Ex vivo intradermal transfection resulted in genomic integration and long-term constitutive gene expression (>150 days). Similarly, efficient intradermal transfection of face and hand flaps in a rat model corroborated this approach. Ex vivo intravascular perfusion of the vector proved inferior to intradermal injection. Conclusions: Intradermal delivery of the transgenes proved superior to intravascular perfusion. Optimization of this gene-delivery approach may allow long-term, constitutive expression of immunomodulatory proteins in face and hand allografts. Future goals include replacement of the luciferase and eGFP reporter genes with key immunomodulatory proteins. (Plast. Reconstr. Surg. 129: 391, 2012.) C1 [Cetrulo, Curtis L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. Univ So Calif, Keck Sch Med, Lab Stem Cell Based Microsurg Tissue Engn, Div Plast & Reconstruct Surg, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Tissue Engn & Regenerat Res Lab, Dept Pathol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Mol Imaging Ctr, Dept Radiol, Los Angeles, CA 90033 USA. Univ Palermo, Sez Chirurg Plast & Ricostruttiva, Dipartimento Discipline Chirurg & Oncol, Palermo, Italy. RP Cetrulo, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM ccetrulo@partners.org FU Department of Surgery of the University of Southern California FX This work was funded by the Willa Lyon Fund of the Department of Surgery of the University of Southern California. The authors thank Dr. Lily Lee and Cathleen Chiu and the Cheng-Ming Chuong Tissue Engineering and Regeneration Research Laboratory at the University of Southern California. In addition, they thank Michelle McVeigh at the University of Southern California Research Center for Liver Diseases for assistance with histology. A special thank you goes to Dr. Leslie P. Weiner from the Department of Neurology at the University of Southern California. NR 21 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 2012 VL 129 IS 2 BP 391 EP 400 DI 10.1097/PRS.0b013e31823aeaeb PG 10 WC Surgery SC Surgery GA 891TR UT WOS:000300240000073 ER PT J AU Trevino, K Fasciano, K Block, S Prigerson, H AF Trevino, K. Fasciano, K. Block, S. Prigerson, H. TI Young Adults with Advanced Cancer: The Relationship Between Social Support and Psychological Well-Being SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Trevino, K.; Fasciano, K.; Block, S.; Prigerson, H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Trevino, K.; Fasciano, K.; Block, S.; Prigerson, H.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 6 EP 7 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800011 ER PT J AU Zadeh, S Wiener, L Battles, H Mullins, L Friebert, S Patenaude, AF Phipps, S Sherman-Bien, S Elkin, TD Madan-Swain, A Kearney, J Bartell, A Kupst, MJ AF Zadeh, S. Wiener, L. Battles, H. Mullins, L. Friebert, S. Patenaude, A. F. Phipps, S. Sherman-Bien, S. Elkin, T. D. Madan-Swain, A. Kearney, J. Bartell, A. Kupst, M. J. TI Health Disparities Related to Marital Status and Perceived Financial Burden SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Zadeh, S.; Wiener, L.; Battles, H.] NCI, NIH, Bethesda, MD 20892 USA. [Mullins, L.] Oklahoma State Univ, Stillwater, OK 74078 USA. [Friebert, S.] Akron Childrens Hosp, Akron, OH USA. [Patenaude, A. F.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Phipps, S.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Sherman-Bien, S.] Miller Childrens Hosp, Long Beach, CA USA. [Elkin, T. D.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Madan-Swain, A.] Univ Alabama, Tuscaloosa, AL USA. [Kearney, J.; Bartell, A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kupst, M. J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 8 EP 9 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800014 ER PT J AU Fasciano, K Trevino, K Waterberg, R Englander, S AF Fasciano, K. Trevino, K. Waterberg, R. Englander, S. TI An Internet Based Psychosocial Resource for Young Adults with Cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Fasciano, K.; Trevino, K.; Waterberg, R.; Englander, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fasciano, K.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 13 EP 14 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800023 ER PT J AU Fernandez-Robles, C AF Fernandez-Robles, C. TI When Psychopharmacology is Not Enough: The Use of Electroconvulsive Therapy in Cancer Patients SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Fernandez-Robles, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 21 EP 21 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800037 ER PT J AU Greenberg, D AF Greenberg, D. TI Psychopharmacological Dilemmas in Cancer Care: APOS Members Bring Their Cases SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Greenberg, D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 21 EP 22 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800038 ER PT J AU Yeh, Y Tofthagen, C AF Yeh, Y. Tofthagen, C. TI Predictors of Colon Cancer Screening Among Older Adults in Florida SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Yeh, Y.; Tofthagen, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tofthagen, C.] Univ S Florida, Tampa, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 22 EP 22 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800039 ER PT J AU Greer, J Pirl, W Gallagher, E Temel, J Lennes, I AF Greer, J. Pirl, W. Gallagher, E. Temel, J. Lennes, I TI Documentation of Intravenous Versus Oral Chemotherapy in Patients With Metastatic Lung Cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Greer, J.; Pirl, W.; Gallagher, E.; Temel, J.; Lennes, I] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 54 EP 55 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800095 ER PT J AU Brand, S Delaney, B Muriel, A Manley, P Liptak, C AF Brand, S. Delaney, B. Muriel, A. Manley, P. Liptak, C. TI Perceived Impact of Social Skills Training Program for Pediatric Brain Tumor Survivors and Caregivers SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Brand, S.; Delaney, B.; Muriel, A.; Manley, P.; Liptak, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 59 EP 60 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800104 ER PT J AU Traeger, L Cannon, S Keating, N Pirl, W Lathan, C Park, E AF Traeger, L. Cannon, S. Keating, N. Pirl, W. Lathan, C. Park, E. TI Prevalence of Depression and Psychosocial Service Utilization Among Non-Hispanic Black and White Lung Cancer Patients SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Traeger, L.; Pirl, W.; Park, E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Traeger, L.; Keating, N.; Pirl, W.; Lathan, C.; Park, E.] Harvard Univ, Sch Med, Boston, MA USA. [Cannon, S.] Univ Massachusetts, Boston, MA 02125 USA. [Keating, N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lathan, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 68 EP 68 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800120 ER PT J AU Bond, B Tan, J Tallis, A Yau, B AF Bond, B. Tan, J. Tallis, A. Yau, B. TI Health and Cancer Beliefs and Attitudes Among Urban Chinese SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Bond, B.; Tan, J.] Bridgewater State Univ, Bridgewater, MA USA. [Tallis, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yau, B.] City Quincy, Quincy, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 76 EP 76 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800134 ER PT J AU Berry, D Yeh, Y Halpenny, B AF Berry, D. Yeh, Y. Halpenny, B. TI Symptom Distress by Education Levels in Ambulatory Patients at a Comprehensive Cancer Center SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Berry, D.; Yeh, Y.; Halpenny, B.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 84 EP 84 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800148 ER PT J AU Tofthagen, C Yeh, Y AF Tofthagen, C. Yeh, Y. TI Sleep Disturbance in Colon Cancer Survivors SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Tofthagen, C.] Univ S Florida, Tampa, FL USA. [Tofthagen, C.] Univ Massachusetts Boston, Boston, MA USA. [Tofthagen, C.; Yeh, Y.] Dana Farber Harvard Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 103 EP 103 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800184 ER PT J AU Traeger, L Park, E Goldstein, E Repper-DeLisi, J Ms, C Jacobo, M Pirl, W AF Traeger, L. Park, E. Goldstein, E. Repper-DeLisi, J. Ms, Convery Jacobo, M. Pirl, W. TI Caring for Patients Undergoing Chemotherapy: Perspectives From Nurses SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Traeger, L.; Park, E.; Goldstein, E.; Repper-DeLisi, J.; Ms, Convery; Jacobo, M.; Pirl, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 112 EP 112 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800201 ER PT J AU Recklitis, C Varela, VS Najita, J Ng, A Mauch, P Parsons, S AF Recklitis, C. Varela, V. S. Najita, J. Ng, A. Mauch, P. Parsons, S. TI The Effect of Self-Enhancement Bias on Survivors' Reports of Psychological Growth After Cancer: A Study of Long-Term Hodgkin's Lymphoma Survivors SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Recklitis, C.; Varela, V. S.; Najita, J.; Ng, A.; Mauch, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ng, A.; Mauch, P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Parsons, S.] Tufts Med Ctr, Boston, MA 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 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 114 EP 115 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800205 ER PT J AU Recklitis, C AF Recklitis, C. TI The Effect of Response Bias on Self-Reported Quality of Life in Adult Survivors of Childhood Cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Recklitis, C.] Dana Farber Canc Inst, Boston, MA 02115 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 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 115 EP 115 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800206 ER PT J AU Braun, I Rao, S Pirl, W AF Braun, I Rao, S. Pirl, W. TI Comparison of Self-Reported Cognitive Difficulties in a National Sample of Long-Term Cancer Survivors and Cancer-Naive Controls SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Braun, I] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rao, S.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Rao, S.] Vet Adm, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Pirl, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 116 EP 117 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800208 ER PT J AU Harvey, HB Pandharipande, PV AF Harvey, H. Benjamin Pandharipande, Pari V. TI The Federal Government's Oversight of CT Safety: Regulatory Possibilities SO RADIOLOGY LA English DT Editorial Material ID PHYSICIANS; RADIOLOGY; MEDICINE; IMPACT; COSTS; TIME; RISK C1 [Harvey, H. Benjamin; Pandharipande, Pari V.] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM pari@mgh-ita.org FU NCI NIH HHS [K07 CA133097, K07CA133097] NR 36 TC 6 Z9 7 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2012 VL 262 IS 2 BP 391 EP 398 DI 10.1148/radiol.11111032 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 892QH UT WOS:000300300200005 PM 22282179 ER PT J AU O'Donnell, DH Abbara, S Chaithiraphan, V Yared, K Killeen, RP Martos, R Keane, D Cury, RC Dodd, JD AF O'Donnell, David H. Abbara, Suhny Chaithiraphan, Vithaya Yared, Kibar Killeen, Ronan P. Martos, Ramon Keane, David Cury, Ricardo C. Dodd, Jonathan D. TI Cardiac MR Imaging of Nonischemic Cardiomyopathies: Imaging Protocols and Spectra of Appearances SO RADIOLOGY LA English DT Review ID CARDIOVASCULAR MAGNETIC-RESONANCE; AMERICAN-HEART-ASSOCIATION; RIGHT-VENTRICULAR CARDIOMYOPATHY; LATE GADOLINIUM ENHANCEMENT; APICAL BALLOONING SYNDROME; TAKO-TSUBO CARDIOMYOPATHY; NORMAL EJECTION FRACTION; SOCIETY-OF-CARDIOLOGY; TASK-FORCE CRITERIA; HYPERTROPHIC CARDIOMYOPATHY AB Recent technologic advances in cardiac magnetic resonance (MR) imaging have resulted in images with high spatial and temporal resolution and excellent myocardial tissue characterization. Cardiac MR is a valuable imaging technique for detection and assessment of the morphology and functional characteristics of the nonischemic cardiomyopathy. It has gained acceptance as a standalone imaging modality that can provide further information beyond the capabilities of traditional modalities such as echocardiography and angiography. Black-blood fast spin-echo MR images allow morphologic assessment of the heart with high spatial resolution, while T2-weighted MR images can depict acute myocardial edema. Contrast material-enhanced images can depict and be used to quantify myocardial edema, infiltration, and fibrosis. This review presents recommended cardiac MR protocols for and the spectrum of imaging appearances of the nonischemic cardiomyopathies. C1 [Killeen, Ronan P.; Martos, Ramon; Keane, David; Dodd, Jonathan D.] St Vincents Univ Hosp, Cardiac CT & MR Imaging Program, Dublin 4, Ireland. [Killeen, Ronan P.; Martos, Ramon; Keane, David; Dodd, Jonathan D.] Univ Coll, Dublin, Ireland. [O'Donnell, David H.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Abbara, Suhny; Chaithiraphan, Vithaya; Yared, Kibar] Ctr Integrat Med & Innovat Technol, Cardiac MR PET CT Program, Boston, MA USA. [Abbara, Suhny; Yared, Kibar] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Abbara, Suhny; Yared, Kibar] Harvard Univ, Sch Med, Boston, MA USA. [Cury, Ricardo C.] Baptist Miami Cardiac & Vasc Inst, Dept Radiol, Miami, FL USA. RP Dodd, JD (reprint author), St Vincents Univ Hosp, Cardiac CT & MR Imaging Program, Dublin 4, Ireland. EM j.dodd@st-vincents.ie FU Astellas; GE Healthcare FX D.H.O. No potential conflicts of interest to disclose. S.A. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: is a consultant for Perceptive Informatics; has received a grant or has a grant pending from Bracco. Other relationships: none to disclose. V.C. No potential conflicts of interest to disclose. K.Y. No potential conflicts of interest to disclose. R.P.K. No potential conflicts of interest to disclose. R.M. No potential conflicts of interest to disclose. D.K. No potential conflicts of interest to disclose. R.C.C. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: is a consultant for Astellas and GE Healthcare; has received grants or has grants pending from Astellas and GE Healthcare. Other relationships: none to disclose. J.D.D. No potential conflicts of interest to disclose. NR 106 TC 18 Z9 18 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2012 VL 262 IS 2 BP 403 EP 422 DI 10.1148/radiol.11100284 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 892QH UT WOS:000300300200007 PM 22282181 ER PT J AU Lee, SI Krishnaraj, A Chatterji, M Dreyer, KJ Thrall, JH Hahn, PF AF Lee, Susanna I. Krishnaraj, Arun Chatterji, Manjil Dreyer, Keith J. Thrall, James H. Hahn, Peter F. TI When Does a Radiologist's Recommendation for Follow-up Result in High-Cost Imaging? SO RADIOLOGY LA English DT Article ID LUNG-CANCER; CT; MANAGEMENT; PROGRESS; SCANS AB Purpose: To measure the proportion of high-cost imaging generated by a radiologist's recommendation and to identify the imaging findings resulting in follow-up. Materials and Methods: This retrospective HIPAA-compliant study had institutional review board approval, with waiver of informed consent. A recommended examination was defined as one performed within a single episode of care (defined as fewer than 60 days after the initial imaging) following a radiologist's recommendation in a prior examination report. Chest and abdominal computed tomography (CT), brain and lumbar spine magnetic resonance (MR) imaging, and body positron emission tomography were included for analysis. From a database of all radiology examinations (approximately 200 000) at one institution over a 6-month period, a computerized search identified all high-cost examinations that were preceded by an examination containing a radiologist recommendation. Medical records were reviewed to verify accuracy of the recommending-recommended examination pairs and to determine the reason for the radiologist's recommendation. For proportions, 95% confidence intervals were calculated. Results: Overall, 1558 of 29 232 (5.3%) high-cost examinations followed a radiologist's recommendation. Chest CT was the high-cost examination most often resulting from a radiologist's recommendation (878 of 9331, 9.4%), followed by abdominal CT (390 of 10 258, 3.8%) and brain MR imaging (222 of 6436, 3.4%). The examination types with the highest numbers of follow-up examinations were chest radiography (n = 431), chest CT (n = 410), abdominal CT (n = 214), and abdominal ultrasonography (n = 120). The most common findings resulting in follow-up were pulmonary nodules or masses (559 of 1558, 35.9%), other pulmonary abnormalities (150 of 1558, 9.6%), adenopathy (103 of 1558, 6.6%), renal lesions (101 of 1558, 6.5%), and negative examination findings (101 of 1558, 6.5%). Conclusion: Radiologists' recommendations account for only a small proportion of outpatient high-cost imaging examinations. Pulmonary nodule follow-up is the most common cause for radiologist-generated examinations. C1 [Lee, Susanna I.; Krishnaraj, Arun; Dreyer, Keith J.; Thrall, James H.; Hahn, Peter F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Chatterji, Manjil] Mt Sinai Med Ctr, Dept Radiol, New York, NY 10029 USA. RP Lee, SI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM slee0@partners.org NR 27 TC 9 Z9 10 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2012 VL 262 IS 2 BP 544 EP 549 DI 10.1148/radiol.11111091 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 892QH UT WOS:000300300200021 PM 22084210 ER PT J AU Pulli, B Schaefer, PW Hakimelahi, R Chaudhry, ZA Lev, MH Hirsch, JA Gonzalez, RG Yoo, AJ AF Pulli, Benjamin Schaefer, Pamela W. Hakimelahi, Reza Chaudhry, Zeshan A. Lev, Michael H. Hirsch, Joshua A. Gonzalez, R. Gilberto Yoo, Albert J. TI Acute Ischemic Stroke: Infarct Core Estimation on CT Angiography Source Images Depends on CT Angiography Protocol SO RADIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-ARTERY OCCLUSION; APPARENT DIFFUSION-COEFFICIENT; TISSUE-PLASMINOGEN ACTIVATOR; 3-DIMENSIONAL FUNCTIONAL CT; BLOOD-FLOW; INTRAARTERIAL THROMBOLYSIS; COMPUTED-TOMOGRAPHY; VOLUME MEASUREMENTS; LESION VOLUME AB Purpose: To test whether the relationship between acute ischemic infarct size on concurrent computed tomographic (CT) angiography source images and diffusion-weighted (DW) magnetic resonance images is dependent on the parameters of CT angiography acquisition protocols. Materials and Methods: This retrospective study had institutional review board approval, and all records were HIPAA compliant. Data in 100 patients with anterior-circulation acute ischemic stroke and large vessel occlusion who underwent concurrent CT angiography and DW imaging within 9 hours of symptom onset were analyzed. Measured areas of hyperintensity at acute DW imaging were used as the standard of reference for infarct size. Information regarding lesion volumes and CT angiography protocol parameters was collected for each patient. For analysis, patients were divided into two groups on the basis of CT angiography protocol differences (patients in group 1 were imaged with the older, slower protocol). Inter-method agreement for infarct size was evaluated by using the Wilcoxon signed rank test, as well as by using Spearman correlation and Bland-Altman analysis. Multivariate analysis was performed to identify predictors of marked (>= 20%) overestimation of infarct size on CT angiography source images. Results: In group 1 (n = 35), median hypoattenuation volumes on CT angiography source images were slightly underestimated compared with DW imaging hyperintensity volumes (33.0 vs 41.6 mL, P = .01; ratio = 0.83), with high correlation (rho = 0.91). In group 2 (n = 65), median volume on CT angiography source images was much larger than that on DW images (94.8 vs 17.8 mL, P < .0001; ratio = 3.5), with poor correlation (rho = 0.49). This overestimation on CT angiography source images would have inappropriately excluded from reperfusion therapy 44.4% or 90.3% of patients eligible according to DW imaging criteria on the basis of a 100-mL absolute threshold or a 20% or greater mismatch threshold, respectively. Atrial fibrillation and shorter time from contrast material injection to image acquisition were independent predictors of marked (>= 20%) infarct size overestimation on CT angiography source images. Conclusion: CT angiography protocol changes designed to speed imaging and optimize arterial opacification are associated with significant overestimation of infarct size on CT angiography source images. (C)RSNA, 2011 C1 [Pulli, Benjamin; Schaefer, Pamela W.; Hakimelahi, Reza; Lev, Michael H.; Gonzalez, R. Gilberto; Yoo, Albert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol, Boston, MA 02114 USA. RP Yoo, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol, 55 Fruit St,Gray 241, Boston, MA 02114 USA. EM ajyoo@partners.org FU Neuroradiology Education and Research Foundation/Boston Scientific; National Institutes of Health [NS050041, NS051343-01A2]; GE Healthcare; CoAxia; Millennium Pharmaceuticals; Penumbra FX A.J.Y. supported by Neuroradiology Education and Research Foundation/Boston Scientific Fellowship in Cerebrovascular Disease Research.; This research was supported by the National Institutes of Health (grants NS050041 and NS051343-01A2).; No potential conflicts of interest to disclose. P. W. S. No potential conflicts of interest to disclose. R. H. No potential conflicts of interest to disclose. Z.A.C. No potential conflicts of interest to disclose. M. H. L. Financial activities related to the present article: received research support from GE Healthcare and consulting fees or honoraria from CoAxia, Millennium Pharmaceuticals, and GE Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. J.A.H. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: has served as a consultant for CareFusion, Atrius, and Phillips; receives royalties from CareFusion; holds stock or stock options in IntraTech and N Focus. Other relationships: none to disclose. R. G. G. No potential conflicts of interest to disclose. A.J.Y. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: has a grant or a grant pending with Penumbra. Other relationships: none to disclose. NR 56 TC 31 Z9 31 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2012 VL 262 IS 2 BP 593 EP 604 DI 10.1148/radiol.11110896 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 892QH UT WOS:000300300200027 PM 22187626 ER PT J AU Andronesi, OC Gagoski, BA Sorensen, AG AF Andronesi, Ovidiu C. Gagoski, Borjan A. Sorensen, A. Gregory TI Neurologic 3D MR Spectroscopic Imaging with Low-Power Adiabatic Pulses and Fast Spiral Acquisition SO RADIOLOGY LA English DT Article ID CHEMICAL-SHIFT; HUMAN BRAIN; IN-VIVO; H-1 MRSI; MULTIPLE-SCLEROSIS; INVERSION-RECOVERY; FOCI PULSES; HIGH-FIELD; SUPPRESSION; NMR AB Purpose: To improve clinical three-dimensional (3D) MR spectroscopic imaging with more accurate localization and faster acquisition schemes. Materials and Methods: Institutional review board approval and patient informed consent were obtained. Data were acquired with a 3-T MR imager and a 32-channel head coil in phantoms, five healthy volunteers, and five patients with glioblastoma. Excitation was performed with localized adiabatic spin-echo refocusing (LASER) by using adiabatic gradient-offset independent adiabaticity wideband uniform rate and smooth truncation (GOIA-W[16,4]) pulses with 3.5-msec duration, 20-kHz bandwidth, 0.81-kHz amplitude, and 45-msec echo time. Interleaved constant-density spirals simultaneously encoded one frequency and two spatial dimensions. Conventional phase encoding (PE) (1-cm(3) voxels) was performed after LASER excitation and was the reference standard. Spectra acquired with spiral encoding at similar and higher spatial resolution and with shorter imaging time were compared with those acquired with PE. Metabolite levels were fitted with software, and Bland-Altman analysis was performed. Results: Clinical 3D MR spectroscopic images were acquired four times faster with spiral protocols than with the elliptical PE protocol at low spatial resolution (1 cm(3)). Higher-spatial resolution images (0.39 cm(3)) were acquired twice as fast with spiral protocols compared with the low-spatial-resolution elliptical PE protocol. A minimum signal-to-noise ratio (SNR) of 5 was obtained with spiral protocols under these conditions and was considered clinically adequate to reliably distinguish metabolites from noise. The apparent SNR loss was not linear with decreasing voxel sizes because of longer local T2* times. Improvement of spectral line width from 4.8 Hz to 3.5 Hz was observed at high spatial resolution. The Bland-Altman agreement between spiral and PE data is characterized by narrow 95% confidence intervals for their differences (0.12, 0.18 of their means). GOIA-W(16,4) pulses minimize chemical-shift displacement error to 2.1%, reduce nonuniformity of excitation to 5%, and eliminate the need for outer volume suppression. Conclusion: The proposed adiabatic spiral 3D MR spectroscopic imaging sequence can be performed in a standard clinical MR environment. Improvements in image quality and imaging time could enable more routine acquisition of spectroscopic data than is possible with current pulse sequences. (C)RSNA, 2011 C1 [Andronesi, Ovidiu C.; Sorensen, A. Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging,Dept Radiol, Boston, MA 02129 USA. [Gagoski, Borjan A.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Andronesi, OC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging,Dept Radiol, 149 13th St,Suite 2301, Boston, MA 02129 USA. EM ovidiu@nmr.mgh.harvard.edu FU Siemens-Massachusetts Institute of Technology Alliance; National Institutes of Health [R01 1200-206456, R01EB007942, R01EB006847] FX Supported by the Siemens-Massachusetts Institute of Technology Alliance.; This research was supported by the National Institutes of Health (grants R01 1200-206456, R01EB007942, and R01EB006847). NR 62 TC 22 Z9 23 U1 0 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2012 VL 262 IS 2 BP 647 EP 661 DI 10.1148/radiol.11110277 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 892QH UT WOS:000300300200032 PM 22187628 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI Overdiagnosis and Screening Mammography Response SO RADIOLOGY LA English DT Letter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 15 Parkman St,Ambulatory Care Bldg,Ste 219, Boston, MA 02114 USA. EM dkopans@partners.org NR 3 TC 0 Z9 0 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2012 VL 262 IS 2 BP 728 EP 729 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 892QH UT WOS:000300300200045 ER PT J AU Lafage, V Ames, C Schwab, F Klineberg, E Akbarnia, B Smith, J Boachie-Adjei, O Burton, D Hart, R Hostin, R Shaffrey, C Wood, K Bess, S AF Lafage, Virginie Ames, Christopher Schwab, Frank Klineberg, Eric Akbarnia, Behrooz Smith, Justin Boachie-Adjei, Oheneba Burton, Douglas Hart, Robert Hostin, Richard Shaffrey, Christopher Wood, Kirkham Bess, Shay CA Int Spine Study Grp TI Changes in Thoracic Kyphosis Negatively Impact Sagittal Alignment After Lumbar Pedicle Subtraction Osteotomy A Comprehensive Radiographic Analysis SO SPINE LA English DT Article DE junctional failure; PSO; pelvic tilt; sagittal imbalance; selective fusion; spinopelvic alignment ID ADULT SCOLIOSIS; FOLLOW-UP; POSTERIOR INSTRUMENTATION; NONOPERATIVE TREATMENT; CLINICAL-OUTCOMES; SPINAL PARAMETERS; IMBALANCE; FUSION; COMPLICATIONS; DEFORMITY AB Study Design. Consecutive, multicenter retrospective review. Objective. To evaluate if change in thoracic kyphosis (TK) has a positive or negative impact on spinopelvic alignment after lumbar pedicle subtraction osteotomy (PSO) with short fusions. Summary of Background Data. In the setting of sagittal malalignment, the effect of large vertebral resections can now be anticipated in long fusions, but their impact on unfused segments (reciprocal changes [RC]) remains poorly understood. Methods. A total of 34 adult patients (mean age = 54 years; SD = 12) who underwent lumbar PSO with upper instrumented vertebra below T10 were included. Radiographic analysis included pre- and postassessment of TK, lumbar lordosis (LL), sagittal vertical axis (SVA), T1 spinopelvic inclination (T1SPI), pelvic tilt (PT), and pelvic incidence (PI). Final SVA and PT were analyzed to determine successful realignment. RC in the thoracic spine was designated favorable or unfavorable on the basis of impact on final SVA and PT. Results. Mean PSO resection was 26 degrees. LL increased from 20 degrees to 49 degrees (P < 0.001). SVA improved from 14 to 4 cm (P < 0.001), and PT improved from 33 degrees to 25 degrees (P < 0.001). Mean increase in TK was 13 degrees (P = 0.002) but was unchanged in 11 patients. Five patients had a favorable RC, and 18 patients had an unfavorable RC. Unfavorable RC was attributed to junctional failure in 6 of 18 patients. Significant differences in the unfavorable RC group included age and greater preoperative PT, PI, SVA, and T1SPI. Conclusion. Significant postoperative alignment changes can occur through unfused thoracic spinal segments after lumbar PSO. Unfavorable RC may limit optimal correction and lead to clinical failures. Risk factors for unfavorable thoracic RC include older patients, larger preoperative PI and PT, and worse preoperative T1SPI and are not simply due to junctional failure. Care should be taken with selective lumbar fusion and PSO in older patients and in those with severe preoperative spinopelvic parameters. C1 [Lafage, Virginie; Schwab, Frank] NYU, Hosp Joint Dis, New York, NY USA. [Klineberg, Eric] Univ Calif Davis, Sacramento, CA 95817 USA. [Akbarnia, Behrooz] San Diego Ctr Spinal Disorders, La Jolla, CA USA. [Ames, Christopher] Univ Calif San Francisco, Med Ctr, San Francisco, CA USA. [Boachie-Adjei, Oheneba] Hosp Special Surg, New York, NY 10021 USA. [Burton, Douglas] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Hart, Robert] Oregon Hlth & Sci Univ, Portland, OR USA. [Hostin, Richard] Baylor Scoliosis Ctr, Plano, TX USA. [Smith, Justin; Shaffrey, Christopher] Univ Virginia, Charlottesville, VA USA. [Wood, Kirkham] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bess, Shay] Rocky Mt Hosp Children, Denver, CO USA. RP Lafage, V (reprint author), 380 2nd Ave,Ste 1001, New York, NY 10010 USA. EM virginie.lafage@gmail.com OI Lafage, Virginie/0000-0002-0119-7111; bess, shay/0000-0002-9697-8999 FU Depuy Spine FX Grant support received by Depuy Spine. Data were gathered from 8 spinal deformity referral centers across the United States. Institutional review board approval was obtained by each participating site. NR 46 TC 37 Z9 40 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD FEB 1 PY 2012 VL 37 IS 3 BP E180 EP E187 DI 10.1097/BRS.0b013e318225b926 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 891OU UT WOS:000300227300007 PM 21673626 ER PT J AU Economopoulos, KP Petralias, A Linos, E Linos, D AF Economopoulos, Konstantinos P. Petralias, Athanasios Linos, Eleni Linos, Dimitrios TI Psychometric Evaluation of Patient Scar Assessment Questionnaire Following Thyroid and Parathyroid Surgery SO THYROID LA English DT Article ID ENDOSCOPIC THYROIDECTOMY; BREAST APPROACH; RELIABILITY; CATEGORIES; COSMESIS; NUMBER AB Background: The Patient Scar Assessment Questionnaire (PSAQ) was constructed to evaluate the effect of any surgical therapy with a linear scar. This study aims to demonstrate reliability and validity of Appearance and Consciousness subscales of PSAQ in patients who underwent thyroidectomy or parathyroidectomy. Methods: Patients who underwent a thyroidectomy or parathyroidectomy between 2000 and 2010 were administered the aforementioned subscales of the PSAQ. Each subscale was separately evaluated for its psychometric performance according to established criteria. Acceptability, reliability, and internal validity analysis were conducted. Results: There were 696 patients (mean age = 51.6 years) who participated in this study. Cronbach's alpha acceptable levels were demonstrated for the Appearance (alpha = 0.79) and Consciousness (alpha = 0.85) subscales. Reliability was also supported for the Appearance (Intraclass Correlation Coefficient [ICC] = 0.79) and Consciousness subscales (ICC = 0.81) by performing test-retest reliability analysis. Individual subscale items' correlations with all subscale scores were acceptable for the Appearance (0.31 to 0.78) and Consciousness (0.23 to 0.81) subscales. Internal validity was supported by evaluating correlations between the global assessment item of each subscale and both summary subscale scores (Appearance: 0.42 to 0.72, Consciousness: 0.66 to 0.67). Conclusions: The Appearance and Consciousness subscales of the PSAQ are both reliable and valid for the assessment of a linear scar following thyroid or parathyroid surgery, independent of the minimally invasive approach being used. C1 [Economopoulos, Konstantinos P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Economopoulos, Konstantinos P.; Linos, Dimitrios] Hygeia Hosp, Dept Surg, Athens, Greece. [Petralias, Athanasios] Athens Univ Econ & Business, Athens, Greece. [Linos, Eleni] Stanford Univ, Med Ctr, Dept Dermatol, Stanford, CA 94305 USA. [Linos, Dimitrios] Univ Athens, Sch Med, GR-11527 Athens, Greece. RP Economopoulos, KP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 2 Hawthorne Pl, Boston, MA 02114 USA. EM economopoulos@sni.gr RI Linos, Eleni/C-4392-2014; OI Linos, Eleni/0000-0002-5856-6301; , Eleni/0000-0003-2538-0700; Economopoulos, Konstantinos/0000-0003-4856-0405 NR 28 TC 10 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD FEB PY 2012 VL 22 IS 2 BP 145 EP 150 DI 10.1089/thy.2011.0265 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 891TY UT WOS:000300240700008 PM 22224816 ER PT J AU Reisner, S Mimiaga, M Bland, SE Driscoll, MA Cranston, K Mayer, KH AF Reisner, Sari Mimiaga, Matthew Bland, Sean E. Driscoll, Maura A. Cranston, Kevin Mayer, Kenneth H. TI PATHWAYS TO EMBODIMENT OF HIV RISK: BLACK MEN WHO HAVE SEX WITH TRANSGENDER PARTNERS, BOSTON, MASSACHUSETTS SO AIDS EDUCATION AND PREVENTION LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PERCEIVED SOCIAL SUPPORT; UNITED-STATES; MULTIDIMENSIONAL SCALE; PREVENTION; BEHAVIORS; INFECTION; FRAMEWORK; SCRIPTS; MSM AB A dearth of research to date has explored HIV risk among Black men who report sex with transgender partners. In 2008, 197 Black men residing in Massachusetts were recruited via modified respondent-driven sampling and completed an interviewer-administered survey. Overall, 8% reported sex with a transgender partner in the past 12 months. Over half (56%) reported unprotected sex during their last encounter with transgender partners. Factors significantly associated with having a transgender sex partner: history of substance abuse, incarceration, PTSD symptoms, lower levels of perceived social support, not having been exposed to HIV prevention services in the past 12 months, and endorsement of mobile van services as a comfortable location to access health care. These formative data suggest that Black men who partner with transgender individuals may be at elevated risk for an array of poorer health-related outcomes, including HIV sexual risk, substance abuse, incarceration, psychosocial vulnerability, and lack of access to health care. Theory-driven interventions that consider the broader context affecting the embodiment of HIV risk are warranted for men who have sex with transgender partners. C1 [Reisner, Sari; Bland, Sean E.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Driscoll, Maura A.; Cranston, Kevin] Massachusetts Dept Publ Hlth, Boston, MA USA. [Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Warren Alpert Sch Med, Providence, RI USA. [Mimiaga, Matthew] Harvard Univ, Sch Publ Hlth, Fenway Inst, Boston, MA 02115 USA. [Mimiaga, Matthew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Reisner, S (reprint author), Fenway Hlth, Fenway Inst, 1340 Boylston St, Boston, MA 02215 USA. EM sreisner@fenwayhealth.org NR 37 TC 5 Z9 5 U1 1 U2 5 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD FEB PY 2012 VL 24 IS 1 BP 15 EP 26 PG 12 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 890BH UT WOS:000300119600002 PM 22339142 ER PT J AU Shahani, L Hartman, C Troisi, C Kapadia, A Giordano, TP AF Shahani, Lokesh Hartman, Christine Troisi, Cathy Kapadia, Asha Giordano, Thomas P. TI Causes of Hospitalization and Perceived Access to Care Among Persons Newly Diagnosed with HIV Infection: Implications for HIV Testing Programs SO AIDS PATIENT CARE AND STDS LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; UNITED-STATES; MEDICAL-CARE; SERVICES UTILIZATION; ADULTS; PREVALENCE; COHORT; SETTINGS; PATTERNS AB There has been little research on the causes of hospitalization when patients are first diagnosed with HIV in the hospital. Reduced access to care could partially explain inpatient diagnosis. We sought to determine if the patients diagnosed as inpatients are hospitalized due to a HIV-related cause versus some other causes, to compare access to care of patients diagnosed with HIV in hospital and outpatient settings, and to determine factors associated with access to care. Participants were newly diagnosed with HIV and recruited between January 2006 and August 2007. The reason for hospitalization was classified as HIV-related, other infectious cause, noninfectious cause, or miscellaneous cause. Access to care was self-reported using a six-item scale and scores were compared with the t test. Multivariate linear regression determined factors associated with improved access to care. Of 185 participants in the study, 78 were diagnosed in hospital and 107 in outpatient settings. Thirty-two percent of participants were female, 90% were racial/ethnic minority, 45% had no high school diploma, and 85% were uninsured. HIV-related conditions accounted for 60% of admissions, followed by non-infectious causes (20%) and other infectious causes (17%). Inpatients did not report less access to care than patients diagnosed while outpatients. Multivariate analysis demonstrated improvement in access to care with better health insurance (p = 0.01) and greater education (p = 0.08). HIV-related preventable conditions account for many hospitalizations when patients are first diagnosed with HIV. While socioeconomic factors are associated with perceived access to care, persons diagnosed in the inpatient setting do not report lower perceived access to care than persons diagnosed as outpatients, suggesting other barriers to earlier diagnosis. C1 [Shahani, Lokesh; Troisi, Cathy; Kapadia, Asha] Univ Texas Hlth Sci Ctr Houston Sch Publ Hlth, Houston, TX USA. [Hartman, Christine; Giordano, Thomas P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Hartman, Christine; Giordano, Thomas P.] Michael E DeBakey VA Med Ctr, Houston Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Troisi, Cathy] City Houston, Dept Hlth & Human Serv, Houston, TX USA. RP Giordano, TP (reprint author), Michael E DeBakey VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tpg@bcm.tmc.edu FU National Institutes of Mental Health [R34MH074360]; Baylor/UTHouston Center for AIDS Research [P30AI036211] FX Supported by National Institutes of Mental Health grant R34MH074360, the Baylor/UTHouston Center for AIDS Research grant P30AI036211, and the facilities and resources of the Harris County Hospital District and the Michael E. DeBakey VA Medical Center. Dr. Giordano is a researcher at the Michael E. DeBakey VA Medical Center Health Services Research and Development Center of Excellence, Houston, Texas. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 32 TC 4 Z9 4 U1 3 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD FEB PY 2012 VL 26 IS 2 BP 81 EP 86 DI 10.1089/apc.2011.0040 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 888KX UT WOS:000300003500003 PM 22149765 ER PT J AU Bhave, PD Hoffmayer, KS Armstrong, EJ Garg, S Patel, A MacGregor, JS Stein, JC Kinlay, S Ganz, P McCabe, JM AF Bhave, Prashant D. Hoffmayer, Kurt S. Armstrong, Ehrin J. Garg, Sonia Patel, Ateet MacGregor, John S. Stein, John C. Kinlay, Scott Ganz, Peter McCabe, James M. TI Predictors of Depressed Left Ventricular Function in Patients Presenting With ST-Elevation Myocardial Infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HEART-FAILURE; RANDOMIZED TRIAL; DYSFUNCTION; MORTALITY; ASSOCIATION; CREATININE; SURVIVAL; BLOCKER AB Early in the course of ST-segment elevation myocardial infarction (STEMI), therapies that may harm patients who develop left ventricular (LV) dysfunction, such as beta-blockers, are often administered. The investigators analyzed the ACTIVATE-SF database, a registry of consecutive STEMI activations presenting to 2 medical centers at the University of California, San Francisco. LV dysfunction was defined as an ejection fraction <= 40% on echocardiography. Of 211 patients included in the analysis, 66 (31%) had LV ejection fractions <= 40%. Patients with LV dysfunction were older (63 +/- 15 vs 56 +/- 13 years, p = 0.002). In multivariate regression models, decreased renal function (reference group, creatinine <1.0 mg/di; adjusted odds ratio [AOR] creatinine >1.5 mg/di 6.35, 95% confidence interval [CI] 1.66 to 24.31, p = 0.007), a history of coronary artery disease (AOR 3.12, 95% CI 1.26 to 7.71, p = 0.014), ST-segment elevation >2 mm on 12-lead electrocardiography (AOR 2.78, 95% CI 1.31 to 5.87, p = 0.008), and need for mechanical ventilation (AOR 3.98, 95% CI 1.41 to 11.19, p = 0.009) increased the odds of LV dysfunction. Inferior ST-segment elevations were associated with 88% decreased odds of LV dysfunction (AOR 0.12, 95% CI 0.06 to 0.35, p <0.001). A prediction score using these characteristics stratified patients into low-, intermediate-, and high-risk groups for LV dysfunction; positive likelihood ratios for LV dysfunction in these groups were 0.07, 1.14, and 4.93, respectively. In conclusion, 5 key predictors of in-hospital LV dysfunction after STEMI were identified; a risk score based on these predictors helps to quickly identify patients presenting with STEW who are at the highest risk for developing significant LV dysfunction and could guide optimal therapeutic choices. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:327-331) C1 [Bhave, Prashant D.] Northwestern Univ, Dept Med, Div Cardiol, Chicago, IL 60611 USA. [Hoffmayer, Kurt S.; Armstrong, Ehrin J.; MacGregor, John S.; Ganz, Peter; McCabe, James M.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Garg, Sonia; Patel, Ateet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Stein, John C.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [MacGregor, John S.; Ganz, Peter] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Kinlay, Scott] VA Boston Healthcare Syst, Div Cardiovasc, Boston, MA USA. RP Bhave, PD (reprint author), Northwestern Univ, Dept Med, Div Cardiol, Chicago, IL 60611 USA. EM pdbhave@gmail.com NR 19 TC 4 Z9 4 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 1 PY 2012 VL 109 IS 3 BP 327 EP 331 DI 10.1016/j.amjcard.2011.09.015 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 888UP UT WOS:000300030400004 PM 22078964 ER PT J AU Roy, B Desai, RV Mujib, M Epstein, AE Zhang, Y Guichard, J Jones, LG Feller, MA Ahmed, MI Aban, IB Love, TE Levesque, R White, M Aronow, WS Fonarow, GC Ahmed, A AF Roy, Brita Desai, Ravi V. Mujib, Marjan Epstein, Andrew E. Zhang, Yan Guichard, Jason Jones, Linda G. Feller, Margaret A. Ahmed, Mustafa I. Aban, Inmaculada B. Love, Thomas E. Levesque, Raynald White, Michel Aronow, Wilbert S. Fonarow, Gregg C. Ahmed, Ali TI Effect of Warfarin on Outcomes in Septuagenarian Patients With Atrial Fibrillation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CHRONIC HEART-FAILURE; CHRONIC KIDNEY-DISEASE; FOLLOW-UP; RHYTHM MANAGEMENT; PROPENSITY SCORE; OLDER-ADULTS; STROKE; HOSPITALIZATION; ASSOCIATION; MORTALITY AB Anticoagulation has been shown to decrease ischemic stroke in atrial fibrillation (AF). However, concerns remain regarding their safety and efficacy in those <= 70 years of age who constitute most patients with AF. Of the 4,060 patients (mean age 65 years, range 49 to 80) in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 2,248 (55% of 4,060) were 70 to 80 years of age, 1,901 of whom were receiving warfarin. Propensity score for warfarin use, estimated for each of the 2,248 patients, was used to match 227 of the 347 patients not on warfarin (in 1:1, 1:2, or 1:3 sets) to 616 patients on warfarin who were balanced in 45 baseline characteristics. All-cause mortality occurred in 18% and 33% of matched patients receiving and not receiving warfarin, respectively, during up to 6 years (mean 3.4) of follow-up (hazard ratio [HR] when warfarin use was compared to its nonuse 0.58, 95% confidence interval [CI] 0.43 to 0.77, p <0.001). All-cause hospitalization occurred in 64% and 67% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use 0.93, 95% CI 0.77 to 1.12, p = 0.423). Ischemic stroke occurred in 4% and 8% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use 0.57, 95% CI 0.31 to 1.04, p = 0.068). Major bleeding occurred in 7% and 10% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use 0.73, 95% CI 0.44 to 1.22, p = 0.229). In conclusion, warfarin use was associated with decreased mortality in septuagenarian patients with AF but had no association with hospitalization or major bleeding. Published by Elsevier Inc. (Am J Cardiol 2012;109:370-377) C1 [Roy, Brita; Mujib, Marjan; Zhang, Yan; Guichard, Jason; Jones, Linda G.; Feller, Margaret A.; Ahmed, Mustafa I.; Aban, Inmaculada B.; Ahmed, Ali] Univ Alabama Birmingham, Birmingham, AL 35229 USA. [Desai, Ravi V.] Lehigh Valley Hosp, Allentown, PA USA. [Epstein, Andrew E.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Epstein, Andrew E.] Univ Penn, Philadelphia, PA 19104 USA. [Jones, Linda G.; Ahmed, Ali] Vet Affairs Med Ctr, Birmingham, AL USA. [Love, Thomas E.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [White, Michel] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Aronow, Wilbert S.] New York Med Coll, Valhalla, NY 10595 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Ahmed, A (reprint author), Univ Alabama Birmingham, Birmingham, AL 35229 USA. EM aahmed@uab.eclu RI Mujib, Marjan/J-2709-2013 OI Mujib, Marjan/0000-0002-3261-8599 FU National Institutes of Health from National Heart, Lung, and Blood Institute, Bethesda, Maryland [R01-HL085561, R01-HL085561-S, R01-HL097047] FX Dr. Ahmed is supported by the National Institutes of Health through Grants R01-HL085561, R01-HL085561-S and R01-HL097047 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland and a generous gift from Ms. Jean B. Morris of Birmingham, Alabama. NR 30 TC 8 Z9 8 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 1 PY 2012 VL 109 IS 3 BP 370 EP 377 DI 10.1016/j.amjcard.2011.09.023 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 888UP UT WOS:000300030400011 PM 22118824 ER PT J AU Acierno, R Rheingold, A Amstadter, A Kurent, J Amella, E Resnick, H Muzzy, W Lejuez, C AF Acierno, Ron Rheingold, Alyssa Amstadter, Ananda Kurent, Jerome Amella, Elaine Resnick, Heidi Muzzy, Wendy Lejuez, Carl TI Behavioral Activation and Therapeutic Exposure for Bereavement in Older Adults SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE complicated bereavement; behavioral activation; therapeutic exposure; major depression; posttraumatic stress disorder; older adults ID BECK DEPRESSION INVENTORY; COMPLICATED GRIEF; CONJUGAL BEREAVEMENT; DISORDER DISTINCT; TRAUMATIC GRIEF; HEALTH; REPLICATION; ANXIETY; SYMPTOMATOLOGY; INTERVENTION AB The development and clinical trial of a 5-session behavioral intervention for complicated bereavement (CB) is presented. We conceptualized CB in terms of Major Depression (MDD) and Post-traumatic Stress Disorder (PTSD) and consequently applied treatment components of Behavioral Activation and Therapeutic Exposure (BA-TE). In order to assure standardization of treatment, control costs, and engage patients, a multi-media, multi-context format was adopted to address avoidance and withdrawal behaviors conceptualized as central pathogenic responses in CB. Participants (N = 26) were assessed before and after BA-TE treatment via structured clinical interview and standardized questionnaires in terms of PTSD, MDD, CB, and health concerns. The number of days since the death of the loved one was widely variable and served as a covariate for all outcome analyses. ANCOVAS revealed statistically significant improvement, irrespective of how many days since death had elapsed prior to initiation of intervention, on structured interviews and self-report measures for most outcome variables. C1 [Acierno, Ron; Rheingold, Alyssa; Kurent, Jerome; Amella, Elaine; Resnick, Heidi; Muzzy, Wendy] Med Univ S Carolina, Charleston, SC 29425 USA. [Acierno, Ron] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Amstadter, Ananda] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Lejuez, Carl] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. RP Acierno, R (reprint author), Med Univ S Carolina, 67 President St,MSC861, Charleston, SC 29425 USA. EM acierno@musc.edu OI Amella, Elaine/0000-0003-4114-429X FU National Institute on Aging [R21-AG023495-01A2] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by a grant from the National Institute on Aging (R21-AG023495-01A2) made to the first author. NR 46 TC 17 Z9 17 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD FEB PY 2012 VL 29 IS 1 BP 13 EP 25 DI 10.1177/1049909111411471 PG 13 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 887MT UT WOS:000299932500004 PM 21685428 ER PT J AU Baird, GS Nelson, SK Keeney, TR Stewart, A Williams, S Kraemer, S Peskind, ER Montine, TJ AF Baird, Geoffrey S. Nelson, Sally K. Keeney, Tracy R. Stewart, Alex Williams, Stephen Kraemer, Stephan Peskind, Elaine R. Montine, Thomas J. TI Age-Dependent Changes in the Cerebrospinal Fluid Proteome by Slow Off-Rate Modified Aptamer Array SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; ALZHEIMERS-DISEASE; MASS-SPECTROMETRY; LUMBAR PUNCTURE; BRAIN; IDENTIFICATION; MENINGITIS; BIOMARKERS; CHEMOKINES; SIGNATURE AB An important precondition for the successful development of diagnostic assays of cerebrospinal fluid (CSF) biomarkers of age-related neurodegenerative diseases is an understanding of the dynamic nature of the CSF proteome during the normal aging process. In this study, a novel proteomic technology was used to quantify hundreds of proteins simultaneously in the CSF from 90 cognitively normal adults 21 to 85 years of age. SomaLogic's highly multiplexed proteomic platform can measure more than 800 proteins simultaneously from small volumes of biological fluids using novel slow off-rate modified aptamer (SOMAmer) protein affinity reagents with sensitivity, specificity, and dynamic ranges that meet or exceed those of enzyme-linked immunosorbent assays. In the first application of this technology to CSF, we detected 248 proteins that possessed signals greater than twofold over background. Several novel correlations between detected protein concentrations and age were discovered that indicate that both inflammation and response to injury in the central nervous system may increase with age. Applying this powerful proteomic approach to CSF provides potential new insight into the aging of the human central nervous system that may have utility in discovering new disease-related changes in the CSF proteome. (Am J Pathol 2012, 180:446-454. DOI: 10.1016/j.ajpath.2011.10.024) C1 [Baird, Geoffrey S.] Univ Washington, Harborview Med Ctr, Dept Lab Med, Seattle, WA 98105 USA. [Baird, Geoffrey S.; Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98105 USA. [Nelson, Sally K.; Keeney, Tracy R.; Stewart, Alex; Williams, Stephen; Kraemer, Stephan] SomaLogic Inc, Boulder, CO USA. [Peskind, Elaine R.] VA Puget Sound Hlth Care Syst, VA NW Network Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Peskind, Elaine R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. RP Baird, GS (reprint author), Univ Washington, Harborview Med Ctr, Dept Lab Med, Box 359743,325 9th Ave, Seattle, WA 98105 USA. EM gbaird@u.washington.edu FU SomaLogic, Inc.; Nancy and Buster Alvord Endowment; Department of Veterans Affairs; NIH [AG05136] FX Supported by funding from SomaLogic, Inc., the Nancy and Buster Alvord Endowment, the Department of Veterans Affairs, an anonymous foundation, and NIH grant AG05136. NR 46 TC 22 Z9 24 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2012 VL 180 IS 2 BP 446 EP 456 DI 10.1016/j.ajpath.2011.10.024 PG 11 WC Pathology SC Pathology GA 887HZ UT WOS:000299918800003 PM 22122984 ER PT J AU Ohishi, M Ono, W Ono, N Khatri, R Marzia, M Baker, EK Root, SH Wilson, TL Iwamototo, Y Kronenberg, HM Aguila, HL Purton, LE Schipani, E AF Ohishi, Masanobu Ono, Wanida Ono, Noriaki Khatri, Richa Marzia, Marilena Baker, Emma K. Root, Sierra H. Wilson, Tremika Le-Shan Iwamototo, Yukihide Kronenberg, Henry M. Aguila, Hector L. Purton, Louise E. Schipani, Ernestina TI A Novel Population of Cells Expressing Both Hematopoietic and Mesenchymal Markers Is Present in the Normal Adult Bone Marrow and Is Augmented in a Murine Model of Marrow Fibrosis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID STEM-CELLS; PRIMARY MYELOFIBROSIS; PARATHYROID-HORMONE; IN-VITRO; HYPERPARATHYROIDISM; OSTEOBLAST; FIBROCYTES; LINEAGE; OSTEOPROGENITORS; DIFFERENTIATION AB Bone marrow (BM) fibrosis is a feature of severe hyperparathyroidism. Consistent with this observation, mice expressing constitutively active parathyroid hormone (PTH)/PTH-related peptide receptors (PPR) in osteoblasts (PPR*Tg) display BM fibrosis. To obtain insight into the nature of BM fibrosis in such a model, a double-mutant mouse expressing constitutively active PPR and green fluorescent protein (GFP) under the control of the type I collagen promoter (PPR*Tg/GFP) was generated. Confocal microscopy and flow cytometry revealed the presence of a cell population expressing GFP (GFP) that was also positive for the hematopoietic marker CD45 in the BM of both PPR*Tg/GFP and control animals. This cell population was expanded in PPR*Tg/GFP. The existence of cells expressing both type I collagen and CD45 in the adult BM was confirmed by IHC and fluorescence-activated cell sorting. An analysis of total RNA extracted from sorted GFP+CD45 cells showed that these cells produced type I collagen and PTH/PTH-related peptide receptor and receptor activator for NF-kappa B mRNAs, further supporting their features of being both mesenchymal and hematopoietic lineages. Similar cells, known as fibrocytes, are also present in pathological fibroses. Our findings, thus, indicate that the BM is a permissive microenvironment for the differentiation of fibrocyte-like cells and raise the possibility that these cells could contribute to the pathogenesis of BM fibrosis. (Am J Pathol 2012, 180:811-818; DOI: 10.1016/j.ajpath.2011.10.028) C1 [Baker, Emma K.; Purton, Louise E.] St Vincents Inst Med Res, Stem Cell Regulat Unit, Fitzroy, Vic 3065, Australia. [Baker, Emma K.; Purton, Louise E.] Univ Melbourne, Dept Med, Fitzroy, Vic 3065, Australia. [Ohishi, Masanobu; Ono, Wanida; Ono, Noriaki; Khatri, Richa; Marzia, Marilena; Wilson, Tremika Le-Shan; Kronenberg, Henry M.; Schipani, Ernestina] Kyushu Univ, Endocrine Unit, Dept Med, Fac Med Sci,Grad Sch Med, Fukuoka 812, Japan. [Ohishi, Masanobu; Iwamototo, Yukihide] Kyushu Univ, Dept Orthopaed Surg, Grad Sch Med, Fac Med Sci, Fukuoka 812, Japan. [Root, Sierra H.; Aguila, Hector L.] Univ Connecticut, Ctr Hlth, Dept Immunol, Farmington, CT USA. [Wilson, Tremika Le-Shan; Schipani, Ernestina] Indiana Univ, Dept Med, Indianapolis, IN USA. [Purton, Louise E.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Purton, Louise E.] Harvard Univ, Sch Med, Boston, MA USA. RP Purton, LE (reprint author), St Vincents Inst Med Res, Stem Cell Regulat Unit, 9 Princes St, Fitzroy, Vic 3065, Australia. EM lpurton@svi.edu.au; eschipan@iupui.edu FU Japan Society for the Promotion of Science; Mochida Memorial Foundation; NIH [RC1HL100569-01, R21AR060689]; National Health and Medical Research Council (NHMRC) [1006485]; Victorian Government FX Supported by the Japan Society for the Promotion of Science (M.O.), the Mochida Memorial Foundation (M.O.), NIH grants RC1HL100569-01 (H.L.A.) and R21AR060689 (E.S.), a grant from the National Health and Medical Research Council (NHMRC; 1006485 to L.E.P.), the Victorian Government's OIS Program (L.E.P.), and an NHMRC Senior Research Fellowship (L.E.P.). NR 32 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2012 VL 180 IS 2 BP 811 EP 818 DI 10.1016/j.ajpath.2011.10.028 PG 8 WC Pathology SC Pathology GA 887HZ UT WOS:000299918800035 PM 22155108 ER PT J AU Maalouf, RM Eid, AA Gorin, YC Block, K Escobar, GP Bailey, S Abboud, HE AF Maalouf, Rita M. Eid, Assaad A. Gorin, Yves C. Block, Karen Escobar, Gladys Patricia Bailey, Steven Abboud, Hanna E. TI Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE cardiac injury; oxidative stress; NADPH oxidases ID NADPH OXIDASE 4; NAD(P)H OXIDASE; MESANGIAL CELLS; FAILING HEART; NOX FAMILY; EXPRESSION; ACTIVATION; APOPTOSIS; REVEALS; MYOFIBROBLASTS AB Maalouf RM, Eid AA, Gorin YC, Block K, Escobar GP, Bailey S, Abboud HE. Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes. Am J Physiol Cell Physiol 302: C597-C604, 2012. First published October 26, 2011; doi: 10.1152/ajpcell.00331.2011.-Oxidative stress contributes to diabetic cardiomyopathy. This study explored the role of the NADPH oxidase Nox4 as a source of reactive oxygen species (ROS) involved in the development of diabetic cardiomyopathy. Phosphorothioated antisense (AS) or sense (S) oligonucleotides for Nox4 were administered for 2 wk to rats made diabetic by streptozotocin. NADPH oxidase activity, ROS generation, and the expression of Nox4, but Nox1 or Nox2, were increased in left ventricular tissue of the diabetic rats. Expression of molecular markers of hypertrophy and myofibrosis including fibronectin, collagen, alpha-smooth muscle actin, and beta-myosin heavy chain were also increased. These parameters were attenuated by the administration of AS but not S Nox4. Moreover, the impairment of contractility observed in diabetic rats was prevented in AS- but not S-treated animals. Exposure of cultured cardiac myocytes to 25 mM glucose [high glucose (HG)] increased NADPH oxidase activity, the expression of Nox4, and molecular markers of cardiac injury. These effects of HG were prevented in cells infected with adenoviral vector containing a dominant negative form of Nox4. This study provides strong evidence that Nox4 is an important source of ROS in the left ventricle and that Nox4-derived ROS contribute to cardiomyopathy at early stages of type 1 diabetes. C1 [Maalouf, Rita M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. [Block, Karen; Abboud, Hanna E.] S Texas Vet Healthcare Syst, San Antonio, TX USA. [Maalouf, Rita M.] Notre Dame Univ, Fac Nat & Appl Sci, Louaize, Lebanon. [Eid, Assaad A.] Amer Univ Beirut, Dept Anat Cell Biol & Physiol, Fac Med, Beirut, Lebanon. RP Maalouf, RM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, M1501,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM rita.maalouf@ndu.edu.lb OI Gorin, Yves/0000-0003-4048-6925 FU Juvenile Diabetes Research Foundation FX Support for these studies was provided by the following sources: Juvenile Diabetes Research Foundation multiproject research grant (to H. E. Abboud, Y. C. Gorin, and K. Block), Advanced Postdoctoral Fellowship from the Juvenile Diabetes Research Foundation (to A. A. Eid). We thank Dr. Mauli Agrawal for help with the final version of the manuscript. NR 37 TC 53 Z9 53 U1 1 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD FEB PY 2012 VL 302 IS 3 BP C597 EP C604 DI 10.1152/ajpcell.00331.2011 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 885OC UT WOS:000299787300012 PM 22031600 ER PT J AU Williams, NM Franke, B Mick, E Anney, RJL Freitag, CM Gill, M Thapar, A O'Donovan, MC Owen, MJ Holmans, P Kent, L Middleton, F Zhang-James, Y Liu, L Meyer, J Nguyen, TT Romanos, J Romanos, M Seitz, C Renner, TJ Walitza, S Warnke, A Palmason, H Buitelaar, J Rommelse, N Vasquez, AA Hawi, Z Langley, K Sergeant, J Steinhausen, HC Roeyers, H Biederman, J Zaharieva, I Hakonarson, H Elia, J Lionel, AC Crosbie, J Marshall, CR Schachar, R Scherer, SW Todorov, A Smalley, SL Loo, S Nelson, S Shtir, C Asherson, P Reif, A Lesch, KP Faraone, SV AF Williams, Nigel M. Franke, Barbara Mick, Eric Anney, Richard J. L. Freitag, Christine M. Gill, Michael Thapar, Anita O'Donovan, Michael C. Owen, Michael J. Holmans, Peter Kent, Lindsey Middleton, Frank Zhang-James, Yanli Liu, Lu Meyer, Jobst Thuy Trang Nguyen Romanos, Jasmin Romanos, Marcel Seitz, Christiane Renner, Tobias J. Walitza, Susanne Warnke, Andreas Palmason, Haukur Buitelaar, Jan Rommelse, Nanda Vasquez, Alejandro Arias Hawi, Ziarih Langley, Kate Sergeant, Joseph Steinhausen, Hans-Christoph Roeyers, Herbert Biederman, Joseph Zaharieva, Irina Hakonarson, Hakon Elia, Josephine Lionel, Anath C. Crosbie, Jennifer Marshall, Christian R. Schachar, Russell Scherer, Stephen W. Todorov, Alexandre Smalley, Susan L. Loo, Sandra Nelson, Stanley Shtir, Corina Asherson, Philip Reif, Andreas Lesch, Klaus-Peter Faraone, Stephen V. TI Genome-Wide Analysis of Copy Number Variants in Attention Deficit Hyperactivity Disorder: The Role of Rare Variants and Duplications at 15q13.3 SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID AUTISM SPECTRUM DISORDER; DEFICIT/HYPERACTIVITY DISORDER; MOLECULAR-GENETICS; ASSOCIATION SCAN; CHROMOSOMAL DELETIONS; NICOTINIC RECEPTOR; CANDIDATE GENE; SCHIZOPHRENIA; ADHD; MICRODUPLICATIONS AB Objective: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology. Method: The authors performed a genome-wide analysis of large, rare CNVs (<1% population frequency) in children with ADHD (N=896) and comparison subjects (N=2,455) from the IMAGE II Consortium. Results: The authors observed 1,562 individually rare CNVs >100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder. Conclusions: These findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5-3.6), this locus could be an important contributor to ADHD etiology. C1 [Faraone, Stephen V.] Cardiff Univ, Med Res Council MRC Ctr Neuropsychiat Genet & Gen, Dept Psychol Med & Neurol, Cardiff, S Glam, Wales. Cardiff Univ, Sch Med, Cardiff, S Glam, Wales. Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. Radboud Univ Nijmegen, Med Ctr, Karakter Child & Adolescent Psychiat Univ Ctr, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. Trinity Coll Dublin, Dept Psychiat, Dublin, Ireland. Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, Frankfurt, Germany. Univ St Andrews, Sch Med, St Andrews KY16 9AJ, Fife, Scotland. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China. Univ Trier, Inst Psychobiol, Dept Neurobehav Genet, Trier, Germany. Univ Marburg, Inst Med Biometry & Epidemiol, Marburg, Germany. Univ Wurzburg, ADHD Clin Res Network, Unit Mol Psychiat, Dept Psychiat Psychosomat & Psychotherapy, D-97070 Wurzburg, Germany. Univ Hosp Munich, Dept Child & Adolescent Psychiat Psychosomat & Ps, Munich, Germany. Saarland Univ Hosp, Dept Child & Adolescent Psychiat, Homburg, Germany. Univ Zurich, Dept Child & Adolescent Psychiat, CH-8006 Zurich, Switzerland. Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. Vrije Univ Amsterdam, Amsterdam, Netherlands. Univ Basel, Inst Psychol, CH-4003 Basel, Switzerland. Aarhus Univ Hosp, Aalborg Psychiat Hosp, Aarhus, Denmark. Univ Ghent, B-9000 Ghent, Belgium. Massachusetts Gen Hosp, Adult ADHD, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat, Ctr Appl Genom, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA. Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Dept Psychiat Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. Univ Toronto, McLaughlin Ctr, Toronto, ON M5S 1A1, Canada. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63130 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Human Genet, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Prevent Med, Keck Sch Med, Los Angeles, CA USA. Kings Coll London, MRC Social Genet & Dev Psychiat, London, England. RP Faraone, SV (reprint author), Cardiff Univ, Med Res Council MRC Ctr Neuropsychiat Genet & Gen, Dept Psychol Med & Neurol, Cardiff, S Glam, Wales. EM williamsnm@cf.ac.uk; sfaraone@childpsychresearch.org RI Buitelaar, Jan/E-4584-2012; Scherer, Stephen /B-3785-2013; Renner, Tobias/I-2120-2013; Holmans, Peter/F-4518-2015; Rommelse, Nanda/D-4872-2009; Liu, Lu/D-8309-2016; Romanos, Marcel/D-7695-2017; Lesch, Klaus-Peter/J-4906-2013; Franke, Barbara/D-4836-2009; Arias Vasquez, Alejandro/E-4762-2012; Howe, Jennifer/I-9013-2012 OI Langley, Kate/0000-0002-2033-2657; O'Donovan, Michael/0000-0001-7073-2379; Walitza, Susanne/0000-0002-8161-8683; Gill, Michael/0000-0003-0206-5337; Kent, Lindsey/0000-0002-5315-3399; Mick, Eric/0000-0001-8505-8145; Anney, Richard/0000-0002-6083-407X; Thapar, Anita/0000-0002-3689-737X; Faraone, Stephen/0000-0002-9217-3982; Hawi, Ziarih/0000-0002-0814-9112; Buitelaar, Jan/0000-0001-8288-7757; Scherer, Stephen /0000-0002-8326-1999; Holmans, Peter/0000-0003-0870-9412; Rommelse, Nanda/0000-0002-1711-0359; Liu, Lu/0000-0003-0194-1454; Lesch, Klaus-Peter/0000-0001-8348-153X; Schachar, Russell/0000-0002-2015-4395; Franke, Barbara/0000-0003-4375-6572; Arias Vasquez, Alejandro/0000-0002-4786-0169; FU Novartis; Shire; Eli Lilly; Elminda; Janssen; McNeil; Fundacion Areces (Spain); Fundacion Dr. Manuel Camelo A.C., Medice Pharmaceuticals; Spanish Child Psychiatry Association; Shionogi Pharma; Cipher Pharmaceuticals; Janssen-Cilag; Vifor; Alcobra; NIH [R13MH059126, R01MH62873, R01MH081803]; Pfizer; Guilford Press; Oxford University Press; Affymetrix Power Award; Wellcome Trust, U.K.; Action Medical Research UK; Radboud University Nijmegen Medical Center; Deutsche Forschungsgemeinschaft [KFO 125, SFB 581, GRK 1156, ME 1923/5-1, ME 1923/5-3, GRK 1389]; Bundesministerium fur Bildung und Forschung (BMBF [01GV0605]; Health Research Board Ireland FX Dr. Freitag has served as speaker or adviser to Desitin, Eli Lilly, and Novartis. Dr. Walitza has served on speakers bureaus for Eli Lilly, Janssen, and AstraZeneca. Dr. Buitelaar has served as a consultant, advisory board member, or speaker for Bristol-Myers Squibb, Janssen Cilag BV, Eli Lilly, Novartis, Schering-Plough, Shire, Servier, and UCB. Dr. Sergeant has received an educational grant from Novartis and has served as speaker or adviser to Janssen-Cilag, Lilly, and Shire. Dr. Roeyers is an advisory board member for Shire and has received research funding and conference attendance support from Shire and Eli Lilly. Dr. Biederman has received research support from Elminda, Janssen, McNeil, and Shire; speaking fees from Fundacion Areces (Spain), Fundacion Dr. Manuel Camelo A.C., Medice Pharmaceuticals, and the Spanish Child Psychiatry Association; consulting fees from Shionogi Pharma and Cipher Pharmaceuticals (honoraria were paid to the Department of Psychiatry at Massachusetts General Hospital [MGH]); honoraria from the MGH Psychiatry Academy for a tuition-funded CME course; an honorarium from Cambridge University Press for a chapter publication; and departmental royalties for a rating scale used for ADHD diagnosis (paid by Eli Lilly, Shire, and AstraZeneca to the Department of Psychiatry at MGH). Dr. Schachar has served as an adviser or consultant to Eli Lilly, Purdue Pharma, and Highland Therapeutics and is named on institutional patents for several genes involved in ADHD and for a stop-task software program. Dr. Asherson has received educational and research grants from Shire, Janssen-Cilag, and Vifor and has served as an adviser to Shire, Janssen-Cilag, Eli Lilly, and Flynn Pharma (all payments used for university educational and research activities). Dr. Faraone has received research support from, served as consultant or adviser to, or participated in CME programs sponsored by Alcobra, Janssen, Eli Lilly, NIH, Novartis, McNeil, Pfizer, and Shire; he receives royalties from Guilford Press and Oxford University Press. All other authors report no financial relationships with commercial interests.; Supported by NIH grants R13MH059126, R01MH62873, and R01MH081803 to Dr. Faraone; an Affymetrix Power Award (2007) to Dr. Franke; a grant from Wellcome Trust, U.K., for sample collection to Dr. Kent; a grant from Wellcome Trust and Action Medical Research UK for sample collection and genotyping to Drs. Thapar, O'Donovan, Holmans, Williams, and Owen; an Internal Grant of Radboud University Nijmegen Medical Center to Dr. Buitelaar; and grants from the Deutsche Forschungsgemeinschaft (KFO 125, SFB 581, GRK 1156 to Dr. Lesch; ME 1923/5-1, ME 1923/5-3 to Drs. Meyer and Freitag; and GRK 1389 to Dr. Meyer) and the Bundesministerium fur Bildung und Forschung (BMBF 01GV0605 to Dr. Lesch). The authors thank the Wellcome Trust and the Health Research Board Ireland for generous support to Drs. Gill, Anney, and Hawi. NR 40 TC 98 Z9 98 U1 0 U2 31 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2012 VL 169 IS 2 BP 195 EP 204 DI 10.1176/appi.ajp.2011.11060822 PG 10 WC Psychiatry SC Psychiatry GA 890BW UT WOS:000300121100015 PM 22420048 ER PT J AU Borad, AJ Allison, GM Wang, D Ahmed, S Karim, MM Kane, AV Moy, J Hibberd, PL Ajjampur, SSR Kang, G Calderwood, SB Ryan, ET Naumova, E Khan, WA Ward, HD AF Borad, Anoli J. Allison, Geneve M. Wang, David Ahmed, Sabeena Karim, Mohammad M. Kane, Anne V. Moy, Joy Hibberd, Patricia L. Ajjampur, Sitara Swarna Rao Kang, Gagandeep Calderwood, Stephen B. Ryan, Edward T. Naumova, Elena Khan, Wasif A. Ward, Honorine D. TI Systemic Antibody Responses to the Immunodominant p23 Antigen and p23 Polymorphisms in Children with Cryptosporidiosis in Bangladesh SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID IMMUNOGLOBULIN-G ANTIBODIES; MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSES; PARVUM INFECTION; SEROLOGICAL RESPONSES; PROTECTIVE IMMUNITY; ENZYME-IMMUNOASSAY; PERUVIAN CHILDREN; IN-VITRO; T-CELL AB Cryptosporidium is a major cause of diarrhea in children in developing countries. However, there is no vaccine available and little is known about immune responses to protective antigens. We investigated antibody responses to p23, a putative vaccine candidate, in children in Bangladesh with cryptosporidiosis and diarrhea (cases) and uninfected children with diarrhea (controls), and p23 gene polymorphisms in infecting species. Serum IgM, IgG, and IgA responses to p23 were significantly greater in cases than controls after three weeks of follow-up. Cases with acute diarrhea had significantly greater serum IgA and IgM responses than those with persistent diarrhea, which suggested an association with protection from prolonged disease. The p23 sequences were relatively conserved among infecting species and subtype families. Although most children were infected with Cryptosporidium hominis, there was a cross-reactive antibody response to C. parvum antigen. These results support further development of p23 as a vaccine candidate. C1 [Ward, Honorine D.] Tufts Med Ctr, Div Geog Med & Infect Dis, Boston, MA 02111 USA. [Borad, Anoli J.] Yale Univ, Sch Med, Dept Med, Div Infect Dis, New Haven, CT 06510 USA. [Allison, Geneve M.; Kane, Anne V.; Moy, Joy; Ward, Honorine D.] Tufts Med Ctr, Dept Med, Div Geog Med & Infect Dis, Boston, MA USA. [Wang, David] Tufts Univ, Sch Engn, Dept Biomed Engn, Medford, MA 02155 USA. [Ahmed, Sabeena; Karim, Mohammad M.; Khan, Wasif A.] Int Ctr Diarrheal Dis Res, Ctr Hlth & Populat Res, Div Clin Sci, Dhaka, Bangladesh. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. [Ajjampur, Sitara Swarna Rao; Kang, Gagandeep] Christian Med Coll & Hosp, Dept Gastrointestinal Sci, Vellore, Tamil Nadu, India. [Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Naumova, Elena] Tufts Univ, Sch Engn, Tufts Initiat Forecasting & Modeling Infect Dis, Medford, MA 02155 USA. RP Ward, HD (reprint author), Tufts Med Ctr, Div Geog Med & Infect Dis, Box 041,800 Washington St, Boston, MA 02111 USA. EM anoli.borad@yale.edu; gallison@tuftsmedicalcenter.org; david.e.wang@gmail.com; sabeena@hotmail.com; mahbubul@icddrb.org; akane@tuftsmedicalcenter.org; joy.moy@gmail.com; phibberd@partners.org; sitararao@cmcvellore.ac.in; gkang@cmcvellore.ac.in; scalderwooci@partners.org; etryan@partners.org; elenamaumova@tufts.edu; wakhan@icddrb.org; hward@tuftsmedicalcenter.org OI Naumova, Elena/0000-0002-9562-4734; Kang, Gagandeep/0000-0002-3656-564X FU National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) [UO1 AI45508, U01 AI058935, RO1 AI52786]; National Center for Complementary and Alternative Medicine, NIH [K24 AT003683]; NIAID, NIH [T32 AI07389]; [T32 AI007438] FX This study was supported by an opportunity pool grant and in part by grants UO1 AI45508, U01 AI058935, and RO1 AI52786 from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) and K24 AT003683 from the National Center for Complementary and Alternative Medicine, NIH. Anoli J. Borad was supported by T32 AI007438, and Geneve M. Allison was supported by T32 AI07389 from NIAID, NIH. NR 62 TC 9 Z9 9 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD FEB PY 2012 VL 86 IS 2 BP 214 EP 222 DI 10.4269/ajtmh.2012.11-0273 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 886PQ UT WOS:000299866700008 PM 22302851 ER PT J AU Palanisami, A Fang, J Lowder, TW Kunz, H Miller, JH AF Palanisami, Akilan Fang, Jie Lowder, Thomas W. Kunz, Hawley Miller, John H., Jr. TI Rapid morphological characterization of isolated mitochondria using Brownian motion SO ANALYTICAL METHODS LA English DT Article ID SKELETAL-MUSCLE MITOCHONDRIA; LASER-INDUCED FLUORESCENCE; CAPILLARY-ELECTROPHORESIS; PHYSICAL-ACTIVITY; WEIGHT-LOSS; RAT HEART; EXERCISE AB Mitochondrial morphology has been associated with numerous pathologies including cancer, diabetes, obesity and heart disease. However, the connection is poorly understood-in part due to the difficulty of characterizing the morphology. This impedes the use of morphology as a tool for disease detection/monitoring. Here, we use the Brownian motion of isolated mitochondria to characterize their size and shape in a high throughput fashion. By using treadmill exercise training, mitochondria from heart and gastrocnemius of Balb/c mice were modulated in size and used to investigate the protocol. Consistent with previous reports, the heart mitochondria of untrained mice increased 5% in diameter immediately after a single bout of moderate exercise ( 1.091 +/- 0.004 mu m) as compared to completely sedentary controls (1.040 +/- 0.022 mu m). In addition, no change was observed in the size of gastrocnemius mitochondria (1.025 +/- 0.018 mu m), which was also in agreement with previous studies. The method was also successfully applied to smaller Saccharomyces cerevisiae mitochondria. C1 [Palanisami, Akilan; Fang, Jie; Miller, John H., Jr.] Univ Houston, Texas Ctr Superconduct, Houston Sci Ctr 202, Houston, TX 77004 USA. [Palanisami, Akilan] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Lowder, Thomas W.; Kunz, Hawley] Univ Houston, Dept Hlth & Human Performance, Houston, TX USA. RP Palanisami, A (reprint author), Univ Houston, Texas Ctr Superconduct, Houston Sci Ctr 202, Houston, TX 77004 USA. EM apalanisami@partners.org; twlowder@uh.edu FU National Heart, Lung, and Blood Institute [R21CA133153]; National Cancer Institute at the NIH; National Science Foundation; ARRA (NIH, NCI) [3 R21 CA133153-03S1]; Texas Center for Superconductivity; Texas Higher Education Coordinating Board; University of Houston FX The authors thank George Mercier and Bryan Spring for helpful discussion. Support was provided by R21CA133153 from the National Heart, Lung, and Blood Institute and the National Cancer Institute at the NIH, the National Science Foundation, and by the ARRA supplement: 3 R21 CA133153-03S1 (NIH, NCI). Additional support was provided by the Texas Center for Superconductivity, the Texas Higher Education Coordinating Board Norman Hackerman Advanced Research Program and a University of Houston internal grant. NR 28 TC 1 Z9 1 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1759-9660 EI 1759-9679 J9 ANAL METHODS-UK JI Anal. Methods PD FEB PY 2012 VL 4 IS 2 BP 513 EP 521 DI 10.1039/c2ay05686k PG 9 WC Chemistry, Analytical; Food Science & Technology; Spectroscopy SC Chemistry; Food Science & Technology; Spectroscopy GA 888XW UT WOS:000300038900032 PM 26435755 ER PT J AU Hariri, LP Gaissert, HA Brown, R Ciaranello, A Greene, RE Selig, MK Kradin, RL AF Hariri, Lida P. Gaissert, Henning A. Brown, Robert Ciaranello, Andrea Greene, Reginald E. Selig, Martin K. Kradin, Richard L. TI Progressive Granulomatous Pneumonitis in Response to Cosmetic Subcutaneous Silicone Injections in a Patient With HIV-1 Infection Case Report and Review of the Literature SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID IMMUNE RESTORATION SYNDROME; TRANSSEXUAL MEN; RECONSTITUTION; MANIFESTATION; FAILURE AB Silicone, commonly used in cosmetic procedures owing to its presumed inertness, can yield serious sequelae including acute embolization and pneumonitis. Chronic pulmonary sequelae in response to silicone injection have not been previously described. We report a case of chronic progressive granulomatous pneumonitis in response to subcutaneous silicone injections in a transgender male-to-female patient infected with human immunodeficiency virus 1 (HIV-1). After receiving silicone injections to the buttock, the patient developed rapid onset dyspnea, pleuritic chest pain, fever, and chills. Chest computed tomography revealed diffuse peripheral interstitial opacities. She responded symptomatically to prednisone with subsequent intermittent symptomatic flares. Four years later, she developed marked dyspnea and cough. Chest computed tomography showed progressive diffuse ground-glass and nodular opacities. Lung biopsies demonstrated numerous spheroid silicone particles within the lung interstitium and small pulmonary vessels, surrounded by foreign body giant cells and nonnecrotizing granulomatous inflammation. We speculate that HIV-1-infected patients may be at risk for chronic, progressive granulomatous pneumonitis due to silicone injection years after their procedure owing to shifting levels of cell-mediated immunity. (Arch Pathol Lab Med. 2012;136:204-207; doi: 10.5858/arpa.2011-0149-CR) C1 [Hariri, Lida P.; Selig, Martin K.; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Brown, Robert; Ciaranello, Andrea; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gaissert, Henning A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Greene, Reginald E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Hariri, LP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren Bldg,Room 219, Boston, MA 02114 USA. EM lhariri@partners.org NR 15 TC 7 Z9 7 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2012 VL 136 IS 2 BP 204 EP 207 DI 10.5858/arpa.2011-0149-CR PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 889DV UT WOS:000300054600018 PM 22288970 ER PT J AU Galkina, EV Butcher, M Keller, SR Goff, M Bruce, A Pei, H Sarembock, IJ Sanders, JM Nagelin, MH Srinivasan, S Kulkarni, RN Hedrick, CC Lattanzio, FA Dobrian, AD Nadler, JL Ley, K AF Galkina, Elena V. Butcher, Matthew Keller, Susanna R. Goff, Matthew Bruce, Anthony Pei, Hong Sarembock, Ian J. Sanders, John M. Nagelin, Melissa H. Srinivasan, Suseela Kulkarni, Rohit N. Hedrick, Catherine C. Lattanzio, Frank A. Dobrian, Anca D. Nadler, Jerry L. Ley, Klaus TI Accelerated Atherosclerosis in Apoe(-/-) Mice Heterozygous for the Insulin Receptor and the Insulin Receptor Substrate-1 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; insulin resistance; leukocytes; vascular biology ID NITRIC-OXIDE SYNTHASE; ENDOTHELIAL-CELLS; METABOLIC SYNDROME; DIABETES-MELLITUS; ANIMAL-MODELS; RESISTANCE; DISEASE; PHOSPHORYLATION; MECHANISMS; MACROPHAGE AB Objective-Prediabetic states are associated with accelerated atherosclerosis, but the availability of mouse models to study connections between these diseases has been limited. The aim of this study was to test the selective role of impaired insulin receptor/insulin receptor substrate-1 signaling on atherogenesis. Methods and Results-To address the effects of impaired insulin signaling associated with hyperinsulinemia on atherosclerosis in the absence of obesity and hyperglycemia, we generated insulin receptor (Insr)/insulin receptor substrate-1 (Insr1) double heterozygous apolipoprotein (Apoe)-knockout mice (Insr(+/-) Irs1(+/-) Apoe(-/-)) mice. Insr(+/-) Irs1(+/-) Apoe(-/-) mice fed a Western diet for 15 weeks showed elevated levels of fasting insulin compared to Insr(+/+) Irs1(+/+) Apoe(-/-) mice. There were no significant differences in glucose, triglyceride, HDL, VLDL, cholesterol levels or free fatty acid in the plasma of Insr(+/-) Irs1(+/-) Apoe(-/-) and Insr(+/+) Irs1(+/+) Apoe(-/-) mice. Atherosclerotic lesions were increased in male (brachiocephalic artery) and female (aortic tree) Insr(+/-) Irs1(+/-) Apoe(-/-) compared to Insr(+/+) Irs1(+/+) Apoe(-/-) mice. Bone marrow transfer experiments demonstrated that nonhematopoietic cells have to be Insr(+/-) Irs1(+/-) to accelerate atherosclerosis. Impaired insulin signaling resulted in decreased levels of vascular phospho-eNOS, attenuated endothelium-dependent vasorelaxation and elevated VCAM-1 expression in aortas of Insr(+/-) Irs1(+/-) Apoe(-/-) mice. In addition, phospho-ERK and vascular smooth muscle cell proliferation were significantly elevated in aortas of Insr(+/-) Irs1(+/-) Apoe(-/-) mice. Conclusion-These results demonstrate that defective insulin signaling is involved in accelerated atherosclerosis in Insr(+/-) Irs1(+/-) Apoe(-/-) mice by promoting vascular dysfunction and inflammation. (Arterioscler Thromb Vasc Biol. 2012;32:247-256.) C1 [Galkina, Elena V.; Butcher, Matthew; Goff, Matthew] Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23501 USA. [Lattanzio, Frank A.; Dobrian, Anca D.] Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23501 USA. [Nadler, Jerry L.] Eastern Virginia Med Sch, Med & Strelitz Diabet Ctr, Norfolk, VA 23501 USA. [Bruce, Anthony; Sanders, John M.; Nagelin, Melissa H.; Srinivasan, Suseela] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA USA. [Keller, Susanna R.] Univ Virginia, Diabet & Hormone Ctr Excellence, Charlottesville, VA USA. [Sarembock, Ian J.] Ohio Heart & Vasc Ctr, Cincinnati, OH USA. [Kulkarni, Rohit N.] Harvard Univ, Med Sch Boston, Joslin Diabet Ctr, Boston, MA USA. [Pei, Hong; Hedrick, Catherine C.; Ley, Klaus] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. RP Galkina, EV (reprint author), Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, POB 1980, Norfolk, VA 23501 USA. EM galkinev@evms.edu RI Hedrick, Catherine/D-1106-2012 FU NIH [HL58108, PO1 HL55798, DK55240]; University of Virginia Diabetes and Endocrine Research Center Animal Characterization Core Facility NIH [DK063609] FX This work was supported by NIH HL58108 (K. L.), PO1 HL55798 (K. L., E. G., J.N., C. C. H. and S. S.), the University of Virginia Diabetes and Endocrine Research Center Animal Characterization Core Facility NIH DK063609 (S. R. K.) and NIH DK55240 (J.N.). NR 42 TC 22 Z9 23 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 2012 VL 32 IS 2 BP 247 EP U172 DI 10.1161/ATVBAHA.111.240358 PG 21 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 879HV UT WOS:000299321200015 PM 22199371 ER PT J AU Sher, L AF Sher, Leo TI What should we tell medical students and residents about euthanasia and assisted suicide? SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; VOLUNTARY EUTHANASIA; MYOCARDIAL-INFARCTION; ACTIVE EUTHANASIA; CANCER-PATIENTS; PHYSICIANS; ATTITUDES; PERSPECTIVE; HEALTH; ILL C1 [Sher, Leo] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. [Sher, Leo] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Leo.Sher@mssm.edu NR 48 TC 4 Z9 4 U1 1 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD FEB PY 2012 VL 46 IS 2 BP 87 EP 91 DI 10.1177/0004867411433894 PG 5 WC Psychiatry SC Psychiatry GA 887BX UT WOS:000299901500004 PM 22311524 ER PT J AU Lee, IS Spector, M AF Lee, In-Seop Spector, Myron TI Coping with copying and conflicts (of interest) SO BIOMEDICAL MATERIALS LA English DT Editorial Material C1 [Lee, In-Seop] Yonsei Univ, Seoul 120749, South Korea. [Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Lee, IS (reprint author), Yonsei Univ, Seoul 120749, South Korea. NR 1 TC 0 Z9 0 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 J9 BIOMED MATER JI Biomed. Mater. PD FEB PY 2012 VL 7 IS 1 AR 010201 DI 10.1088/1748-6041/7/1/010201 PG 2 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 888NZ UT WOS:000300011900001 ER PT J AU Macaya, D Spector, M AF Macaya, D. Spector, M. TI Injectable hydrogel materials for spinal cord regeneration: a review SO BIOMEDICAL MATERIALS LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; PEPTIDE NANOFIBER SCAFFOLD; NEURAL PROGENITOR CELLS; MYELIN-ASSOCIATED GLYCOPROTEIN; COLLAGEN GELS; NEURITE OUTGROWTH; DRUG-DELIVERY; CROSS-LINKING; WALLERIAN DEGENERATION; AXONAL REGENERATION AB Spinal cord injury (SCI) presents a complex regenerative problem due to the multiple facets of growth inhibition that occur following trauma to the cord parenchyma and stroma. Clinically, SCI is further complicated by the heterogeneity in the size, shape and extent of human injuries. Many of these injuries do not breach the dura mater and have continuous viable axons through the injury site that can later lead to some degree of functional recovery. In these cases, surgical manipulation of the spinal cord by implanting a preformed scaffold or drug delivery device may lead to further damage. Given these circumstances, in situ-forming scaffolds are an attractive approach for SCI regeneration. These synthetic and natural polymers undergo a rapid transformation from liquid to gel upon injection into the cord tissue, conforming to the individual lesion site and directly integrating with the host tissue. Injectable materials can be formulated to have mechanical properties that closely match the native spinal cord extracellular matrix, and this may enhance axonal ingrowth. Such materials can also be loaded with cellular and molecular therapeutics to modulate the wound environment and enhance regeneration. This review will focus on the current status of in situ-forming materials for spinal cord repair. The advantages of, and requirements for, such polymers will be presented, and examples of the behavior of such systems in vitro and in vivo will be presented. There are helpful lessons to be learned from the investigations of injectable hydrogels for the treatment of SCI that apply to the use of these biomaterials for the treatment of lesions in other central nervous system tissues and in organs comprising other tissue types. C1 [Macaya, D.; Spector, M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Macaya, D.] Harvard Massachusetts Inst Technol, Cambridge, MA USA. RP Macaya, D (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. EM mspector@rics.bwh.harvard.edu FU NSF; VA Research Career Scientist Award; US Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service FX DM was supported by an NSF Fellowship, and MS by a VA Research Career Scientist Award. The work reported here was supported by the US Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. NR 156 TC 71 Z9 73 U1 22 U2 147 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 J9 BIOMED MATER JI Biomed. Mater. PD FEB PY 2012 VL 7 IS 1 AR 012001 DI 10.1088/1748-6041/7/1/012001 PG 22 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 888NZ UT WOS:000300011900003 PM 22241481 ER PT J AU Genkinger, JM Li, RF Spiegelman, D Anderson, KE Albanes, D Bergkvist, L Bernstein, L Black, A van den Brandt, PA English, DR Freudenheim, JL Fuchs, CS Giles, GG Giovannucci, E Goldbohm, RA Horn-Ross, PL Jacobs, EJ Koushik, A Mannisto, S Marshall, JR Miller, AB Patel, AV Robien, K Rohan, TE Schairer, C Stolzenberg-Solomon, R Wolk, A Ziegler, RG Smith-Warner, SA AF Genkinger, Jeanine M. Li, Ruifeng Spiegelman, Donna Anderson, Kristin E. Albanes, Demetrius Bergkvist, Leif Bernstein, Leslie Black, Amanda van den Brandt, Piet A. English, Dallas R. Freudenheim, Jo L. Fuchs, Charles S. Giles, Graham G. Giovannucci, Edward Goldbohm, R. Alexandra Horn-Ross, Pamela L. Jacobs, Eric J. Koushik, Anita Mannisto, Satu Marshall, James R. Miller, Anthony B. Patel, Alpa V. Robien, Kim Rohan, Thomas E. Schairer, Catherine Stolzenberg-Solomon, Rachael Wolk, Alicja Ziegler, Regina G. Smith-Warner, Stephanie A. TI Coffee, Tea, and Sugar-Sweetened Carbonated Soft Drink Intake and Pancreatic Cancer Risk: A Pooled Analysis of 14 Cohort Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PAST MEDICAL HISTORY; ALCOHOL-CONSUMPTION; UNITED-STATES; REGRESSION-MODELS; GLYCEMIC LOAD; LIFE-STYLE; GREEN TEA; BEVERAGE CONSUMPTION; CALIFORNIA TEACHERS; DIABETES-MELLITUS AB Background: Coffee has been hypothesized to have pro- and anticarcinogenic properties, whereas tea may contain anticarcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, whereas findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous. Methods: In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random-effects model. Results: No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR = 1.10; 95% CI, 0.81-1.48 comparing >= 900 to <0 g/d; 237g approximate to 8oz), tea (MVRR = 0.96; 95% CI, 0.78-1.16 comparing >= 400 to 0 g/d; 237g approximate to 8oz), or SSB (MVRR = 1.19; 95% CI, 0.98-1.46 comparing >= 250 to 0 g/d; 355g approximate to 12oz; P value, test for between-studies heterogeneity > 0.05). These associations were consistent across levels of sex, smoking status, and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR = 1.06; 95% CI, 1.02-1.12). Conclusion and Impact: Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB. Cancer Epidemiol Biomarkers Prev; 21(2); 305-18. (C)2011 AACR. C1 [Genkinger, Jeanine M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Li, Ruifeng; Spiegelman, Donna; Giovannucci, Edward; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. [Giovannucci, Edward; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Fuchs, Charles S.; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA USA. [Anderson, Kristin E.; Robien, Kim] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Anderson, Kristin E.; Robien, Kim] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Albanes, Demetrius; Black, Amanda; Schairer, Catherine; Stolzenberg-Solomon, Rachael; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Bergkvist, Leif] Cent Hosp Vasteras, Dept Surg, Vasteras, Sweden. [Bergkvist, Leif] Cent Hosp Vasteras, Clin Res Ctr, Vasteras, Sweden. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. [van den Brandt, Piet A.] Maastricht Univ, Sch Oncol & Dev Biol GROW, Dept Epidemiol, Maastricht, Netherlands. [English, Dallas R.; Giles, Graham G.] Univ Melbourne, Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [English, Dallas R.; Giles, Graham G.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Freudenheim, Jo L.; Marshall, James R.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Goldbohm, R. Alexandra] TNO Qual Life, Dept Prevent & Hlth, Leiden, Netherlands. [Horn-Ross, Pamela L.] No Calif Canc Ctr, Fremont, CA USA. [Jacobs, Eric J.; Patel, Alpa V.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Koushik, Anita] Univ Montreal, Dept Med Sociale & Prevent, Montreal, PQ, Canada. [Mannisto, Satu] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. [Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Wolk, Alicja] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. RP Genkinger, JM (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St,Rm 803, New York, NY 10032 USA. EM jg3081@columbia.edu RI Albanes, Demetrius/B-9749-2015; OI Mannisto, Satu/0000-0002-8668-3046; Robien, Kim/0000-0002-2120-2280; Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188 FU NIH [CA098566, CA55075, CA139578] FX This work was supported by NIH grants CA098566, CA55075, and CA139578. NR 110 TC 26 Z9 30 U1 2 U2 22 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2012 VL 21 IS 2 BP 305 EP 318 DI 10.1158/1055-9965.EPI-11-0945-T PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 889KT UT WOS:000300073300009 PM 22194529 ER PT J AU Chan, AT Arber, N Burn, J Chia, WK Elwood, P Hull, MA Logan, RF Rothwell, PM Schror, K Baron, JA AF Chan, Andrew T. Arber, Nadir Burn, John Chia, Whay Kuang Elwood, Peter Hull, Mark A. Logan, Richard F. Rothwell, Peter M. Schroer, Karsten Baron, John A. TI Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview SO CANCER PREVENTION RESEARCH LA English DT Review ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LOW-DOSE ASPIRIN; FAMILIAL ADENOMATOUS POLYPOSIS; RANDOMIZED CONTROLLED-TRIAL; SERVICES-TASK-FORCE; LONG-TERM USE; TRANSIENT ISCHEMIC ATTACK; DOUBLE-BLIND TRIAL; PRIMARY PREVENTION; COLON-CANCER AB Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term posttrial follow-up of nearly 14,000 patients from four randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about five years was associated with a 34% reduction in 20-year CRC mortality. A separate metaanalysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in four randomized adenoma prevention trials showed that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least two years, there was a 50% or more reduction in the risk of CRC commencing five years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin's anticancer effect require further investigation. Cancer Prev Res; 5(2); 164-78. (C) 2011 AACR. C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Arber, Nadir] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Canc Prevent, IL-69978 Tel Aviv, Israel. [Arber, Nadir] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Burn, John] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Chia, Whay Kuang] Natl Canc Ctr Singapore, Dept Med Oncol, Singapore, Singapore. [Elwood, Peter] Cardiff Univ, Univ Wales Hosp, Dept Epidemiol Stat & Publ Hlth, Cardiff, S Glam, Wales. [Hull, Mark A.] St James Univ Hosp, Leeds Inst Mol Med, Leeds, W Yorkshire, England. [Logan, Richard F.] Univ Nottingham, Univ Hosp, Div Epidemiol & Publ Hlth, Nottingham NG7 2RD, England. [Rothwell, Peter M.] John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Stroke Prevent Res Unit, Oxford OX3 9DU, England. [Schroer, Karsten] Univ Dusseldorf, Univ Klinikum Dusseldorf, Inst Pharmakol & Klin Pharmakol, D-40225 Dusseldorf, Germany. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM achan@partners.org RI Mavoa, Suzanne/B-5372-2010; OI Burn, John/0000-0002-9823-2322 FU Bayer, Berlin, Germany; SLA Pharma FX The authors thank Shinkan Tokudome, NIHealth and Nutrition, Shinjuku-ku, Tokyo, Japan; Hideki Ishikawa, Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto, and Prefectural University of Medicine, Osaka, Japan; Raghib Ali, INDOX Cancer Research Network, University of Oxford, Oxford, United Kingdom; Gabriela Moslein, St. Josef's Hospital Bochum Linden, Nordrhein-Westfalen, Germany; Carlo Patrono, Department of Pharmacology, Catholic University School of Medicine, Rome, Italy, for their contributions. Editorial assistance and preparation of figures was supported by Bayer, Berlin, Germany.; M. Hull has received commercial grants from SLA Pharma. A.T. Chan is a Damon Runyon Cancer Research Foundation Clinical Investigator. NR 116 TC 97 Z9 97 U1 1 U2 15 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 FEB PY 2012 VL 5 IS 2 BP 164 EP 178 DI 10.1158/1940-6207.CAPR-11-0391 PG 15 WC Oncology SC Oncology GA 888ZO UT WOS:000300043500003 PM 22084361 ER PT J AU Hudish, TM Opincariu, LI Mozer, AB Johnson, MS Cleaver, TG Malkoski, SP Merrick, DT Keith, RL AF Hudish, Tyler M. Opincariu, Laura I. Mozer, Anthony B. Johnson, Micah S. Cleaver, Timothy G. Malkoski, Stephen P. Merrick, Daniel T. Keith, Robert L. TI N-nitroso-tris-chloroethylurea Induces Premalignant Squamous Dysplasia in Mice SO CANCER PREVENTION RESEARCH LA English DT Article ID INDUCED LUNG CARCINOGENESIS; CHEMICALLY-INDUCED MODEL; TRANSCRIPTION FACTOR-I; CELL CARCINOMA; K-RAS; TUMORS; CANCER; NEOPLASMS; ADENOCARCINOMAS; EXPRESSION AB Squamous cell carcinoma (SCC) and premalignant endobronchial lesions have been difficult to study in murine models. In this study, we evaluate the topical N-nitroso-tris-chloroethylurea (NTCU) murine SCC model, determine the extent to which resulting premalignant airway dysplasia develops, discuss clinicopathologic grading criteria in lesion progression, and confirm that immunohistochemical (IHC) staining patterns are consistent with those observed in human endobronchial dysplasia and SCC. Male and female FVB mice were treated biweekly with topical NTCU (4, 8, or 40 mmol/L) or vehicle for 32 weeks. Following sacrifice, squamous cell lesions were enumerated and categorized into the following groups: flat atypia, low-grade dysplasia, high-grade dysplasia, and invasive SCC. The 40 mmol/L NTCU concentration produced the entire spectrum of premalignant dysplasias and squamous cell carcinomas, but was associated with poor survival. Concentrations of 4 and 8 mmol/L NTCU were better tolerated and produced only significant levels of flat atypia. Squamous origin of the range of observed lesions was confirmed with IHC staining for cytokeratin 5/6, p63, thyroid transcription factor-1 (TTF-1), and Napsin-A. This study shows that topical application of high-dose NTCU produces endobronchial premalignant lesions with classic squamous characteristics and should allow for improved preclinical evaluation of potential chemopreventive agents. Cancer Prev Res; 5(2); 283-9. (C) 2011 AACR. C1 [Hudish, Tyler M.; Opincariu, Laura I.; Mozer, Anthony B.; Johnson, Micah S.; Merrick, Daniel T.; Keith, Robert L.] Denver VA Med Ctr, Dept Med, Denver, CO 80220 USA. [Cleaver, Timothy G.; Malkoski, Stephen P.; Keith, Robert L.] Univ Colorado Denver, Dept Med, Aurora, CO USA. RP Keith, RL (reprint author), Denver VA Med Ctr, Dept Med, 1055 Clermont St,Box 151, Denver, CO 80220 USA. EM robert.keith@va.gov FU Department of Veterans Affairs; NCI [K08-CA131483] FX This work was supported by Department of Veterans Affairs Merit Review Program (R.L. Keith) and NCI Grant K08-CA131483 (S.P. Malkoski). NR 34 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD FEB PY 2012 VL 5 IS 2 BP 283 EP 289 DI 10.1158/1940-6207.CAPR-11-0257 PG 7 WC Oncology SC Oncology GA 888ZO UT WOS:000300043500015 PM 22086679 ER PT J AU Wang, SH Wu, JS Suburu, J Gu, ZN Cai, JZ Axanova, LS Cramer, SD Thomas, MJ Perry, DL Edwards, IJ Mucci, LA Sinnott, JA Loda, MF Sui, GC Berquin, IM Chen, YQ AF Wang, Shihua Wu, Jiansheng Suburu, Janel Gu, Zhennan Cai, Jiaozhong Axanova, Linara S. Cramer, Scott D. Thomas, Michael J. Perry, Donna L. Edwards, Iris J. Mucci, Lorelei A. Sinnott, Jennifer A. Loda, Massimo F. Sui, Guangchao Berquin, Isabelle M. Chen, Yong Q. TI Effect of dietary polyunsaturated fatty acids on castration-resistant Pten-null prostate cancer SO CARCINOGENESIS LA English DT Article ID ANDROGEN RECEPTOR GENE; TUMOR-SUPPRESSOR; DEPRIVATION THERAPY; CELL-LINES; IN-VIVO; EXPRESSION; AMPLIFICATION; FISH; INACTIVATION; PTEN/MMAC1 AB A common treatment of advanced prostate cancer involves the deprivation of androgens. Despite the initial response to hormonal therapy, eventually all the patients relapse. In the present study, we sought to determine whether dietary polyunsaturated fatty acid (PUFA) affects the development of castration-resistant prostate cancer. Cell culture, patient tissue microarray, allograft, xenograft, prostate-specific Pten knockout and omega-3 desaturase transgenic mouse models in conjunction with dietary manipulation, gene knockdown and knockout approaches were used to determine the effect of dietary PUFA on castration-resistant Pten-null prostate cancer. We found that deletion of Pten increased androgen receptor (AR) expression and Pten-null prostate cells were castration resistant. Omega-3 PUFA slowed down the growth of castration-resistant tumors as compared with omega-6 PUFA. Omega-3 PUFA decreased AR protein to a similar extent in tumor cell cytosolic and nuclear fractions but had no effect on AR messenger RNA level. Omega-3 PUFA treatment appeared to accelerate AR protein degradation, which could be blocked by proteasome inhibitor MG132. Knockdown of AR significantly slowed down prostate cancer cell proliferation in the absence of androgens. Our data suggest that omega-3 PUFA inhibits castration-resistant prostate cancer in part by accelerating proteasome-dependent degradation of the AR protein. Dietary omega-3 PUFA supplementation in conjunction with androgen ablation may significantly delay the development of castration-resistant prostate cancer in patients compared with androgen ablation alone. C1 [Wang, Shihua; Wu, Jiansheng; Suburu, Janel; Gu, Zhennan; Cai, Jiaozhong; Axanova, Linara S.; Cramer, Scott D.; Sui, Guangchao; Berquin, Isabelle M.; Chen, Yong Q.] Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. [Thomas, Michael J.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27157 USA. [Perry, Donna L.; Edwards, Iris J.] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. [Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Sinnott, Jennifer A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Loda, Massimo F.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chen, YQ (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA. EM yqchen@wakehealth.edu FU American Institute for Cancer Research [07B087]; National Institutes of Health [R21CA124511, R01CA107668, P01CA106742] FX American Institute for Cancer Research (07B087) and National Institutes of Health (R21CA124511, R01CA107668 and P01CA106742). NR 37 TC 17 Z9 17 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 2012 VL 33 IS 2 BP 404 EP 412 DI 10.1093/carcin/bgr290 PG 9 WC Oncology SC Oncology GA 888YF UT WOS:000300039800023 PM 22159221 ER PT J AU Chang, I Liu, J Majid, S Saini, S Zaman, MS Yamamura, S Shahryari, V Chiyomaru, T Deng, GR Dahiya, R Tanaka, Y AF Chang, Inik Liu, Jan Majid, Shahana Saini, Sharanjot Zaman, Mohd S. Yamamura, Soichiro Shahryari, Varahram Chiyomaru, Takeshi Deng, Guoren Dahiya, Rajvir Tanaka, Yuichiro TI Catechol-O-methyltransferase-mediated metabolism of 4-hydroxyestradiol inhibits the growth of human renal cancer cells through the apoptotic pathway SO CARCINOGENESIS LA English DT Article ID ESTRADIOL-INDUCED TUMORIGENESIS; HAMSTER-KIDNEY; OXIDATIVE STRESS; EPITHELIAL-CELLS; DOWN-REGULATION; MESSENGER-RNA; EXPRESSION; ESTROGENS; GENE; MEN AB Long-term exposure to estrogen and its metabolites may play an important role in renal cell carcinogenesis. Catechol-O-methyltransferase (COMT) participates in the estrogen metabolism pathway by neutralizing toxic substances. Although reduced COMT activity has been suggested to be a risk factor for estrogen-associated cancers, no studies have investigated the biological significance of COMT in the pathogenesis of human renal cell cancers (RCCs). We initially found that COMT levels are significantly decreased in human RCC tissues and cells suggesting it plays a suppressive role in tumor development. However, transient overexpression of COMT has no functional effect on RCC cell lines. In contrast, when cells overexpressing COMT are treated with its substrate 4-hydroxyestradiol (4-OHE2), growth is inhibited by apoptotic cell death. We also found that COMT overexpression combined with 4-OHE2 induces upregulation of growth arrest- and DNA damage-inducible protein alpha (GADD45 alpha). We further show that downregulation of GADD45 alpha by a small interfering RNA-mediated approach inhibits cell death, indicating the essential role of GADD45 alpha in the underlying mechanism of COMT action in response to 4-OHE2. Finally, 4-methoxyestradiol fully reproduces the antiproliferative function of COMT with 4-OHE2 by promoting GADD45 alpha induction. Together, these findings show that COMT in the presence of 4-OHE2 prevents RCC cell proliferation by enhancing apoptosis and that GADD45 alpha plays a critical role in the COMT-mediated inhibition of RCC. C1 [Tanaka, Yuichiro] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94121 USA. RP Tanaka, Y (reprint author), San Francisco VA Med Ctr, Dept Urol, 4150 Clement St, San Francisco, CA 94121 USA. EM yuichiro.tanaka@ucsf.edu FU Veterans Affairs Merit Review grant FX This study was supported by the Veterans Affairs Merit Review grant. NR 39 TC 5 Z9 5 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 2012 VL 33 IS 2 BP 420 EP 426 DI 10.1093/carcin/bgr294 PG 7 WC Oncology SC Oncology GA 888YF UT WOS:000300039800025 PM 22159223 ER PT J AU Shapiro, S Traiger, GL Turner, M McGoon, MD Wason, P Barst, RJ AF Shapiro, Shelley Traiger, Glenna L. Turner, Michelle McGoon, Michael D. Wason, Prieya Barst, Robyn J. TI Sex Differences in the Diagnosis, Treatment, and Outcome of Patients With Pulmonary Arterial Hypertension Enrolled in the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management SO CHEST LA English DT Article ID CLINICAL CLASSIFICATION; REVEAL REGISTRY; SURVIVAL AB Background: Pulmonary arterial hypertension (PAH) is a life-threatening disease that affects more women than men. The reasons for the female preponderance are unclear, and there are limited data available for men with PAH. Methods: Data from the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) were analyzed to explore sex differences among patients with PAH with regard to 2-year survival from enrollment and 5-year survival from time of diagnosis. Results: The data set included 2,318 women and 651 men. More women had PAH associated with connective tissue disease (P < .001), and more men had portopulmonary hypertension (P <.001) and HIV-associated PAH (P < .001). More women had congenital heart disease-associated PAH (P = .017), thyroid disease (P < .001), and depression reported (P <= .001). At diagnosis, men had higher mean pulmonary artery pressure (53 +/- 14 vs 51 +/- 14.3 mm Fig; P = .013) and mean right atrial pressure (10 6 vs 9 6 mm Hg; P = .031). Women had better survival estimates for 2 years from enrollment and for 5 years from diagnosis. Stratifying by age showed that survival from enrollment was similar between men and women aged <60 years at enrollment, whereas men aged >= 60 years have lower survival rates compared with women aged >= 60 years. Conclusions: Our findings highlight similarities and differences between men and women with PAH, raising questions for future exploration regarding the role of hormones and sex in causation and survival in PAH. C1 [Shapiro, Shelley; Traiger, Glenna L.] Univ Calif Los Angeles, VA Greater LA Healthcare Syst, Los Angeles, CA 90073 USA. David Geffen Univ Calif, Los Angeles Sch Med, Los Angeles, CA USA. [Turner, Michelle] ICON Late Phase & Outcomes Res, San Francisco, CA USA. [McGoon, Michael D.] Mayo Clin, Rochester, MN USA. [Wason, Prieya] Actel Pharmaceut US Inc, San Francisco, CA USA. [Barst, Robyn J.] Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Shapiro, S (reprint author), Univ Calif Los Angeles, VA Greater LA Healthcare Syst, 11301 Wilshire Blvd,Cardiol Sect 111E, Los Angeles, CA 90073 USA. EM sshapiro@ucla.edu FU Actelion Pharmaceuticals US, Inc.; Actelion; Pfizer; Gilead; United Therapeutics; Bayer; Medtronic; Eli Lilly Co.; NIH/NHLBI; Novartis FX Funding for the REVEAL Registry is provided by Actelion Pharmaceuticals US, Inc.; The authors have reported to CHEST the following conflicts of interest: Dr Shapiro has received research grants from Actelion, Pfizer, Gilead, United Therapeutics, and Bayer. Dr Shapiro has served as a consultant for Gilead and United Therapeutics and as a speaker for Actelion, United Therapeutics, and Gilead. Ms Traiger serves as a consultant and is on the speakers' bureau for Actelion, United Therapeutics, and Gilead. Ms Turner is employed by ICON Late Phase & Outcomes Research, a company that receives research support from Actelion and other pharmaceutical companies. Dr McGoon serves as a consultant for Actelion, Gilead, Lung Rx, and Medtronic. Dr McCoon has received grants from Gilead and Medtronic. Dr McGoon has received honoraria for his service on the REVEAL Steering Committee, which is supported by Actelion. Ms Wason is employed by Actelion Pharmaceuticals US, Inc. Dr Barst serves as a consultant for and has received honoraria from Actelion, Bayer, GlaxoSmithKline, Gilead, Eli Lilly & Co., Merck, Novartis, and Pfizer. Dr Barst has received grants from Actelion, Gilead, Eli Lilly & Co., NIH/NHLBI, Novartis, and Pfizer. Dr Barst has received honoraria for her service on the REVEAL Steering Committee, which is supported by Actelion. NR 17 TC 40 Z9 42 U1 1 U2 11 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD FEB PY 2012 VL 141 IS 2 BP 363 EP 373 DI 10.1378/chest.10-3114 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 887HQ UT WOS:000299917900013 PM 21757572 ER PT J AU Howington, JA Gunnarsson, CL Maddaus, MA McKenna, RJ Meyers, BF Miller, D Moore, M Rizzo, JA Swanson, S AF Howington, John A. Gunnarsson, Candace L. Maddaus, Michael A. McKenna, Robert J. Meyers, Bryan F. Miller, Daniel Moore, Matthew Rizzo, John A. Swanson, Scott TI In-hospital Clinical and Economic Consequences of Pulmonary Wedge Resections for Cancer Using Video-Assisted Thoracoscopic Techniques vs Traditional Open Resections SO CHEST LA English DT Article ID THORACIC-SURGERY; LUNG-CANCER; LOBECTOMY; NODULE; THORACOTOMY; EXPERIENCE; MANAGEMENT; DIAGNOSIS; TRIALS; VATS AB Objective: The objective of this study was to compare the safety, use, and cost profiles of open thoracotomy vs video-assisted thoracoscopic surgery (VATS) for wedge resection in lung cancer performed by thoracic surgeons in the United States. Methods: The Premier database, which contains complete patient billing, hospital cost, and coding histories from > 25 million inpatient discharges and > 175 million hospital outpatient visits, was used for this analysis. Eligible patients were those who underwent wedge resection by a thoracic surgeon for cancer diagnosis or treatment through open thoracotomy or VATS in 2007 or 2008. Multivariable logistic regression analyses were run for binary outcomes, and ordinary least squares regressions were used for continuous outcomes. All models were adjusted for patient demographics, comorbid conditions, and hospital characteristics. Results: Of 8,228 eligible procedures, 2,051 patients underwent wedge resections by a thoracic surgeon using the open technique (n = 999) or VATS (n = 1,052). Hospital costs remained significantly higher for open wedge resections than for VATS ($17,377 vs $14,795, P = .000). Surgery time was significantly longer for open resections vs VATS (3.16 vs 2.82 h). Length of stay was 6.34 days for open vs 4.44 days for VATS. Adverse events were significant in the multivariable analysis, with an OR of 1.57 (95% CI, 1.29-1.91) in favor of VATS. Conclusions: Although this retrospective database analysis could not address the issue of oncologic outcome equivalence, a clear advantage of VATS over open wedge lung cancer resection was found for both acute clinical outcomes and hospital costs. CHEST 2012; 141(2):429-435 C1 [Gunnarsson, Candace L.] S2 Stat Solut Inc, Cincinnati, OH 45241 USA. [Howington, John A.] NorthShore Univ Hlth Syst, Div Thorac Surg, Evanston, IL USA. [Howington, John A.] NorthShore Univ Hlth Syst, Div Surg Qual, Evanston, IL USA. [Maddaus, Michael A.] Univ Minnesota, Div Thorac Surg, Duluth, MN 55812 USA. [McKenna, Robert J.] Cedars Sinai Med Ctr, Div Thorac Surg, Los Angeles, CA 90048 USA. [Meyers, Bryan F.] Washington Univ, Div Cardiothorac Surg, St Louis, MO USA. [Miller, Daniel] Emory Clin, Div Thorac Surg, Atlanta, GA 30322 USA. [Moore, Matthew] Ethicon Endosurg Inc, Healthcare Policy & Econ, Cincinnati, OH USA. [Rizzo, John A.] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [Rizzo, John A.] SUNY Stony Brook, Dept Econ, Stony Brook, NY 11794 USA. [Swanson, Scott] Brigham & Womens Hosp, Div Minimally Invas Thorac Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gunnarsson, CL (reprint author), S2 Stat Solut Inc, 11176 Main St, Cincinnati, OH 45241 USA. EM Candaceg@s2stats.com FU Ethicon Endo-Surgery, Inc, Cincinnati, Ohio FX Funding for this study was provided by Ethicon Endo-Surgery, Inc, Cincinnati, Ohio. NR 17 TC 14 Z9 14 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD FEB PY 2012 VL 141 IS 2 BP 429 EP 435 DI 10.1378/chest.10-3013 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 887HQ UT WOS:000299917900021 PM 21778260 ER PT J AU Melamed, ML Thadhani, RI AF Melamed, Michal L. Thadhani, Ravi I. TI Vitamin D Therapy in Chronic Kidney Disease and End Stage Renal Disease SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID D-RECEPTOR ACTIVATION; RANDOMIZED CONTROLLED-TRIALS; INCIDENT DIALYSIS PATIENTS; SUDDEN CARDIAC DEATH; HEMODIALYSIS-PATIENTS; D DEFICIENCY; 25-HYDROXYVITAMIN-D LEVELS; MINERAL METABOLISM; D SUPPLEMENTATION; CHOLECALCIFEROL SUPPLEMENTATION AB Vitamin D has garnered much research and debate about supplementation in recent years, not only as it pertains to patients with kidney disease but also to those in the general population. This review discusses observational and available clinical trial evidence about the effects of both calcitriol and vitamin D analogs (active) and ergocalciferol and cholecalciferol (nutritional) vitamin D in patients with CKD and ESRD. Clin J Am Soc Nephrol 7: 358-365, 2012. doi: 10.2215/CJN.04040411 C1 [Melamed, Michal L.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. [Melamed, Michal L.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Thadhani, Ravi I.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. RP Melamed, ML (reprint author), Albert Einstein Coll Med, Dept Med, 1300 Morris Pk Ave,Ullmann Bldg,Room 615, Bronx, NY 10461 USA. EM michalmelamed@yahoo.com FU National Institutes of Health [K23 DK078774, R01 DK080123, R01 DK087783, R21HL102882, R01DK084974]; Abbott Laboratories FX M.L.M. is supported by Grants K23 DK078774, R01 DK080123, and R01 DK087783, and R.I.T. is supported by Grants R21HL102882 and R01DK084974, all from the National Institutes of Health.; R.I.T. is supported by a research grant from Abbott Laboratories and has received reimbursement for travel expenses by Abbott Laboratories. NR 69 TC 31 Z9 32 U1 0 U2 8 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD FEB PY 2012 VL 7 IS 2 BP 358 EP 365 DI 10.2215/CJN.04040411 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 890DC UT WOS:000300124300024 PM 22193236 ER PT J AU Johnson, SL Murray, G Fredrickson, B Youngstrom, EA Hinshaw, S Bass, JM Deckersbach, T Schooler, J Salloum, I AF Johnson, Sheri L. Murray, Greg Fredrickson, Barbara Youngstrom, Eric A. Hinshaw, Stephen Bass, Julie Malbrancq Deckersbach, Thilo Schooler, Jonathan Salloum, Ihsan TI Creativity and bipolar disorder: Touched by fire or burning with questions? SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review DE Creativity; Bipolar disorder; Mania ID HYPOMANIC PERSONALITY SCALE; POSITIVE EMOTIONS; LITHIUM-CARBONATE; MENTAL-ILLNESS; 1ST-DEGREE RELATIVES; MANIC-DEPRESSION; MOOD DISORDERS; HEDONIC TONE; I DISORDER; IMPULSIVITY AB Substantial literature has linked bipolar disorder with creative accomplishment. Much of the thinking in this area has been inspired by biographical accounts of poets, musicians, and other highly accomplished groups, which frequently document signs of bipolar disorder in these samples. A smaller literature has examined quantitative measures of creativity among people with bipolar disorder or at risk for the disorder. In this paper, we provide a critical review of such evidence. We then consider putative mechanisms related to the link of bipolar disorder with creativity, by drawing on literature outside of bipolar disorder on personality, motivational, and affective predictors of creativity. Because so little research has directly evaluated whether these factors could help explain the elevations of creativity in bipolar disorder, we conclude with an agenda for future research on the theoretically and clinically compelling topic of creativity in bipolar disorder. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Johnson, Sheri L.; Hinshaw, Stephen; Bass, Julie Malbrancq] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Murray, Greg] Swinburne Univ Technol, Melbourne, Vic, Australia. [Fredrickson, Barbara; Youngstrom, Eric A.] Univ N Carolina, Chapel Hill, NC USA. [Deckersbach, Thilo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schooler, Jonathan] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. [Salloum, Ihsan] Univ Miami, Dept Psychiat & Human Behav, Coral Gables, FL 33124 USA. RP Johnson, SL (reprint author), Univ Calif Berkeley, 3210 Tolman Hall, Berkeley, CA 94720 USA. EM SLJohnson@berkeley.edu RI johnson, sheri/D-8712-2014 OI johnson, sheri/0000-0002-9945-4816 FU NIMH NIH HHS [R01 MH076021] NR 162 TC 33 Z9 33 U1 17 U2 60 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD FEB PY 2012 VL 32 IS 1 BP 1 EP 12 DI 10.1016/j.cpr.2011.10.001 PG 12 WC Psychology, Clinical SC Psychology GA 888EY UT WOS:000299987800001 PM 22088366 ER PT J AU Leira, R Sobrino, T Blanco, M Campos, F Rodriguez-Yanez, M Castellanos, M Moldes, O Millan, M Davalos, A Castillo, J AF Leira, Rogelio Sobrino, Tomas Blanco, Miguel Campos, Francisco Rodriguez-Yanez, Manuel Castellanos, Mar Moldes, Octavio Millan, Monica Davalos, Antoni Castillo, Jose TI A higher body temperature is associated with haemorrhagic transformation in patients with acute stroke untreated with recombinant tissue-type plasminogen activator (rtPA) SO CLINICAL SCIENCE LA English DT Article DE biomarkers; blood brain barrier (BBB); haemorrhagic transformation (HT); ischaemic stroke; temperature ID ACUTE ISCHEMIC-STROKE; CEREBRAL-ARTERY OCCLUSION; THROMBOLYTIC THERAPY; BRAIN TEMPERATURE; MATRIX METALLOPROTEINASES; INTRACEREBRAL HEMORRHAGE; MODERATE HYPOTHERMIA; ATRIAL-FIBRILLATION; URGENT THERAPY; HYPERTHERMIA AB Higher body temperature is a prognostic factor of poor outcome in acute stroke. Our aim was to study the relationship between body temperature, HT (haemorrhagic transformation) and biomarkers of BBB (blood brain barrier) damage in patients with acute ischaemic stroke untreated with rtPA (recombinant tissue-type plasminogen activator). We studied 229 patients with ischaemic stroke <12 h from symptom onset. Body temperature was determined at admission and every 6 h during the first 3 days. HT was evaluated according to ECASS II (second European Co-operative Acute Stroke Study) criteria in a multimodal MRI (magnetic resonance imaging) at 72 h. We found that 55 patients (34.1%) showed HT. HT was associated with cardioembolic stroke (64.2% against 23.0%; P <0.0001), higher body temperature during the first 24 h (36.9 degrees C compared with 36.5 degrees C; P <0.0001), more severe stroke [NIHSS (National Institutes of Health Stroke Scale) score, 14 (9-20) against 10 (7-15); P = 0.002], and greater DWI (diffusion-weighted imaging) lesion volume at admission (23.2 cc compared with 13.2 cc; P <0.0001). Plasma MMP-9 (matrix metalloproteinase 9) (187.3 ng/ml compared with 44.2 ng/ml; P < 0.0001) and cFn (cellular fibronectin) levels (16.3 mu g/ml compared with 7.1 mu g/ml; P = 0.001) were higher in patients with HT. Body temperature within the first 24 h was independently associated with HT {OR (odds ratio), 7.3 [95% Cl (confidence interval), 2.4-22.6]; P < 0.0001} after adjustment for cardioembolic stroke subtype, baseline NIHSS score and DWI lesion volume. This effect remained unchanged after controlling for MMP-9 and cFn. In conclusion, high body temperature within the first 24 h after ischaemic stroke is a risk factor for HT in patients untreated with rtPA. This effect is independent of some biological signatures of BBB damage. C1 [Leira, Rogelio; Sobrino, Tomas; Blanco, Miguel; Campos, Francisco; Rodriguez-Yanez, Manuel; Moldes, Octavio; Castillo, Jose] Univ Santiago de Compostela, Hosp Clin Univ, Clin Neurosci Res Lab, Dept Neurol, Santiago De Compostela, Spain. [Campos, Francisco] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Castellanos, Mar] Hosp Univ Doctor Josep Trueta, Biomed Res Inst Girona, Dept Neurol, Stroke Unit, Girona, Spain. [Millan, Monica; Davalos, Antoni] Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, Dept Neurosci, E-08193 Barcelona, Spain. RP Castillo, J (reprint author), Univ Santiago de Compostela, Hosp Clin Univ, Clin Neurosci Res Lab, Dept Neurol, Santiago De Compostela, Spain. EM jose.castillo@usc.es RI Sobrino, Tomas/D-2498-2017; OI Sobrino, Tomas/0000-0002-9760-8690; Castillo, Jose/0000-0002-6685-3001; Castellanos, Maria del mar/0000-0003-3116-1352 FU Spanish Ministry of Science and Innovation [SAF2011-30517]; Fondo de Investigaciones Sanitarias; Instituto Salud Carlos III [RETICS-RD06/0026, PI08 1472]; Xunta de Galicia (Conselleria de Innovacion, Industria e Comercio) [10PXIB918282PR]; Conselleria de Sanidade [PS09/32]; Fundacion Mutua Madrilena FX This work was supported, in part, by the Spanish Ministry of Science and Innovation [grant number SAF2011-30517], Fondo de Investigaciones Sanitarias, Instituto Salud Carlos III [grant numbers RETICS-RD06/0026 and PI08 1472], Xunta de Galicia (Conselleria de Innovacion, Industria e Comercio [grant number 10PXIB918282PR]; Conselleria de Sanidade: [grant number PS09/32]; and Programa Angeles Alvarino), and Fundacion Mutua Madrilena. NR 47 TC 6 Z9 6 U1 1 U2 6 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD FEB PY 2012 VL 122 IS 3-4 BP 113 EP 119 DI 10.1042/CS20110143 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 890CW UT WOS:000300123700003 PM 21861843 ER PT J AU Bennett, SM Ehrenreich-May, J Litz, BT Boisseau, CL Barlow, DH AF Bennett, Shannon M. Ehrenreich-May, Jill Litz, Brett T. Boisseau, Christina L. Barlow, David H. TI Development and Preliminary Evaluation of a Cognitive-Behavioral Intervention for Perinatal Grief SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article DE perinatal loss; prolonged grief; cognitive behavioral therapy ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; COMPLICATED GRIEF; PREGNANCY LOSS; EMOTIONAL DISORDERS; TRANSDIAGNOSTIC TREATMENT; FUTURE-DIRECTIONS; UNIFIED PROTOCOL; NEONATAL DEATH; ANXIETY AB Perinatal loss, typically defined as fetal death beyond 20 weeks gestation through infant death 1-month postpartum, is a potentially traumatizing experience for parents occurring in approximately 1% of births in the United States. Although many women recover; 15% to 25% have enduring grief-related symptomatology and functional impairment. Perinatal grief is a unique bereavement experience, but clinical resources for detecting and treating severe perinatal grief are rare and interventions are largely without empirical support. We developed and pilot tested a cognitive-behavioral intervention targeting the psychological and behavioral sequelae of perinatal bereavement. To initially evaluate the feasibility and efficacy of the intervention, 5 women who suffered a perinatal loss were randomized to a 2-week, 4-week, or 6-week baseline period in a multiple-baseline single-case experimental design. In most cases, after the respective baseline periods, there was a steady decline in reported grief symptoms. These gains were largely maintained at a 6-week follow-up assessment. This study provides initial evidence in support of future research and clinical efforts tailoring cognitive behavioral interventions to meet the specific needs of women who experience perinatal loss. C1 [Ehrenreich-May, Jill] Univ Miami, Coral Gables, FL 33124 USA. [Litz, Brett T.; Barlow, David H.] Boston Univ, Boston, MA 02215 USA. [Litz, Brett T.] VA Boston Hlth Care Syst, Boston, MA USA. [Boisseau, Christina L.] Brown Med Sch, Providence, RI USA. [Boisseau, Christina L.] Butler Hosp, Providence, RI 02906 USA. EM smb9017@med.cornell.edu NR 53 TC 7 Z9 7 U1 3 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FEB PY 2012 VL 19 IS 1 BP 161 EP 173 PG 13 WC Psychology, Clinical SC Psychology GA 885SH UT WOS:000299800600017 ER PT J AU Kleinerman, R Eisen, DB Ibrahimi, OA AF Kleinerman, Rebecca Eisen, Daniel B. Ibrahimi, Omar A. TI Re: Sentinel Node Biopsy Should Be Offered in Thin Melanoma with Mitotic Rate Greater than One SO DERMATOLOGIC SURGERY LA English DT Letter ID EARLY-STAGE MELANOMA; THERAPEUTIC UTILITY; CUTANEOUS MELANOMA; COST-EFFECTIVENESS; LYMPHADENECTOMY; MICROMETASTASES; MICROANATOMY; POSITIVITY; ACCURACY; STANDARD C1 [Kleinerman, Rebecca; Eisen, Daniel B.] Univ Calif Davis, Dept Dermatol, Sacramento, CA 95817 USA. [Ibrahimi, Omar A.] Univ Connecticut, Ctr Hlth, Dept Dermatol, Farmington, CT USA. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Kleinerman, R (reprint author), Univ Calif Davis, Dept Dermatol, Sacramento, CA 95817 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD FEB PY 2012 VL 38 IS 2 BP 290 EP 292 DI 10.1111/j.1524-4725.2011.02269.x PG 3 WC Dermatology; Surgery SC Dermatology; Surgery GA 887RD UT WOS:000299945600027 PM 22309640 ER PT J AU Zhang, KB Li, L Qi, YJ Zhu, XP Gan, BY DePinho, RA Averitt, T Guo, SD AF Zhang, Kebin Li, Ling Qi, Yajuan Zhu, Xiaoping Gan, Boyi DePinho, Ronald A. Averitt, Travis Guo, Shaodong TI Hepatic Suppression of Foxo1 and Foxo3 Causes Hypoglycemia and Hyperlipidemia in Mice SO ENDOCRINOLOGY LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; FACTOR-BINDING PROTEIN-1; INSULIN-RESPONSE SEQUENCE; REGULATES LIPID-METABOLISM; GENE-EXPRESSION; KINASE-B; PHOSPHOENOLPYRUVATE CARBOXYKINASE; NUTRIENT HOMEOSTASIS; GLUCOSE-PRODUCTION; SIGNALING CASCADE AB Dysregulation of blood glucose and triglycerides are the major characteristics of type 2 diabetes mellitus. We sought to identify the mechanisms regulating blood glucose and lipid homeostasis. Cell-based studies established that the Foxo forkhead transcription factors Forkhead box O (Foxo)-1, Foxo3, and Foxo4 are inactivated by insulin via a phosphatidylinositol 3-kinase/Akt-dependent pathway, but the role of Foxo transcription factors in the liver in regulating nutrient metabolism is incompletely understood. In this study, we used the Cre/LoxP genetic approach to delete the Foxo1, Foxo3, and Foxo4 genes individually or a combination of two or all in the liver of lean or db/db mice and assessed the role of Foxo inactivation in regulating glucose and lipid homeostasis in vivo. In the lean mice or db/db mice, hepatic deletion of Foxo1, rather than Foxo3 or Foxo4, caused a modest reduction in blood glucose concentrations and barely affected lipid homeostasis. Combined deletion of Foxo1 and Foxo3 decreased blood glucose levels, elevated serum triglyceride and cholesterol concentrations, and increased hepatic lipid secretion and caused hepatosteatosis. Analysis of the liver transcripts established a prominent role of Foxo1 in regulating gene expression of gluconeogenic enzymes and Foxo3 in the expression of lipogenic enzymes. Our findings indicate that Foxo1 and Foxo3 inactivation serves as a potential mechanism by which insulin reduces hepatic glucose production and increases hepatic lipid synthesis and secretion in healthy and diabetic states. (Endocrinology 153: 631-646, 2012) C1 [Guo, Shaodong] Cent Texas Vet Hlth Care Syst, Texas A&M Hlth Sci Ctr, Cardiovasc Res Inst, Div Mol Cardiol,Coll Med,Dept Med, Temple, TX 76504 USA. [Gan, Boyi; DePinho, Ronald A.] Harvard Univ, Belfer Inst Appl Canc Sci, Dana Farber Canc Inst, Dept Med Oncol,Med Sch, Boston, MA 02115 USA. [Gan, Boyi; DePinho, Ronald A.] Harvard Univ, Belfer Inst Appl Canc Sci, Dana Farber Canc Inst, Dept Med,Med Sch, Boston, MA 02115 USA. [Gan, Boyi; DePinho, Ronald A.] Harvard Univ, Belfer Inst Appl Canc Sci, Dana Farber Canc Inst, Dept Genet,Med Sch, Boston, MA 02115 USA. RP Guo, SD (reprint author), Cent Texas Vet Hlth Care Syst, Texas A&M Hlth Sci Ctr, Cardiovasc Res Inst, Div Mol Cardiol,Coll Med,Dept Med, 1901 S 1st St,Bldg 205, Temple, TX 76504 USA. EM sguo@medicine.tamhsc.edu RI zhu, xiaoping/A-3979-2013 FU Children's Hospital Boston; American Diabetes Association Junior Faculty [JF-7-07-27]; American Heart Association [BGIA7880040]; Texas A&M Heath Science Center FX We thank Drs. Morris F. White and Joseph Majzoub (Children's Hospital Boston) for their support and Dr. Kenneth M. Baker and his group for reading the manuscript. The GeneChips experiments were performed at the Children's Hospital Boston Molecular Genetic Core Facility, and plasma fatty acids measurements were performed at Lipomics Technologies, Inc. (West Sacramento, CA). We also thank Dr. C. Z. Wu (Dana Farber Cancer Institute, Boston, MA) for dCHIP and data statistical analysis.; This work was supported by the American Diabetes Association Junior Faculty Grant JF-7-07-27, the American Heart Association Grant BGIA7880040, and the Texas A&M Heath Science Center Start-up Funds (to S.G.). NR 57 TC 50 Z9 57 U1 1 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2012 VL 153 IS 2 BP 631 EP 646 DI 10.1210/en.2011-1527 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 887LF UT WOS:000299928200013 PM 22147007 ER PT J AU Nehs, MA Nucera, C Nagarkatti, SS Sadow, PM Morales-Garcia, D Hodin, RA Parangi, S AF Nehs, Matthew A. Nucera, Carmelo Nagarkatti, Sushruta S. Sadow, Peter M. Morales-Garcia, Dieter Hodin, Richard A. Parangi, Sareh TI Late Intervention with anti-BRAF(V600E) Therapy Induces Tumor Regression in an Orthotopic Mouse Model of Human Anaplastic Thyroid Cancer SO ENDOCRINOLOGY LA English DT Article ID PHASE-II TRIAL; BRAF MUTATION; BRAF(V600E); PROGRESSION; CARCINOMA; KINASE; RAF; INHIBITORS; CELLS; IDENTIFICATION AB Human anaplastic thyroid cancer (ATC) is a lethal disease with an advanced clinical presentation and median survival of 3 months. The BRAF(V600E) oncoprotein is a potent transforming factor that causes human thyroid cancer cell progression in vitro and in vivo; therefore, we sought to target this oncoprotein in a late intervention model of ATC in vivo. We used the human ATC cell line 8505c, which harbors the BRAF(V600E) and TP53(R248G) mutations. Immunocompromised mice were randomized to receive the selective anti-BRAF(V600E) inhibitor, PLX4720, or vehicle by oral gavage 28 d after tumor implantation, 1 wk before all animals typically die due to widespread metastatic lung disease and neck compressive symptoms in this model. Mice were euthanized weekly to evaluate tumor volume and metastases. Control mice showed progressive tumor growth and lung metastases by 35 d after tumor implantation. At that time, all control mice had large tumors, were cachectic, and were euthanized due to their tumor-related weight loss. PLX4720-treated mice, however, showed a significant decrease in tumor volume and lung metastases in addition to a reversal of tumor-related weight loss. Mouse survival was extended to 49 d in PLX4720-treated animals. PLX4720 treatment inhibited cell cycle progression from 28 d to 49 d in vivo. PLX4720 induces striking tumor regression and reversal of cachexia in an in vivo model of advanced thyroid cancer that harbors the BRAF(V600E) mutation. (Endocrinology 153: 985-994, 2012) C1 [Nehs, Matthew A.; Nucera, Carmelo; Nagarkatti, Sushruta S.; Morales-Garcia, Dieter; Hodin, Richard A.; Parangi, Sareh] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Surg Unit,Thyroid Canc Res Lab, Boston, MA 02115 USA. [Nucera, Carmelo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol,Div Canc Biol & Angiogenesis, Boston, MA 02115 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Parangi, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Surg Unit,Thyroid Canc Res Lab, Wang ACC 460,15 Parkman St, Boston, MA 02115 USA. EM sparangi@partners.org FU National Institutes of Health [1R01CA149738-01, 5T32 DK007754-10]; Italian Ministry of Education, Universities and Research (MIUR); A. Gemelli Medical School (Catholic University, Rome, Italy) FX This work was funded by National Institutes of Health Grants 1R01CA149738-01 (to S.P.) and 5T32 DK007754-10 (to R.H.). C.N. is an M.D. and recipient of Ph.D. fellowship supported from the Italian Ministry of Education, Universities and Research (MIUR) and carried out at Harvard Medical School; he was also funded through A. Gemelli Medical School (Catholic University, Rome, Italy). NR 37 TC 30 Z9 30 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2012 VL 153 IS 2 BP 985 EP 994 DI 10.1210/en.2011-1519 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 887LF UT WOS:000299928200045 PM 22202162 ER PT J AU Hoffmann, B Luttmann-Gibson, H Cohen, A Zanobetti, A de Souza, C Foley, C Suh, HH Coull, BA Schwartz, J Mittleman, M Stone, P Horton, E Gold, DR AF Hoffmann, Barbara Luttmann-Gibson, Heike Cohen, Allison Zanobetti, Antonella de Souza, Celine Foley, Christopher Suh, Helen H. Coull, Brent A. Schwartz, Joel Mittleman, Murray Stone, Peter Horton, Edward Gold, Diane R. TI Opposing Effects of Particle Pollution, Ozone, and Ambient Temperature on Arterial Blood Pressure SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollution; ambient temperature; blood pressure; diabetes mellitus; epidemiology; ozone; particles ID PARTICULATE AIR-POLLUTION; SYSTEMIC INFLAMMATION; EXPOSURE; MATTER; ASSOCIATION; HYPERTENSION; MEDIATORS; DISEASE; HEALTH; RISK AB BACKGROUND: Diabetes increases the risk of hypertension and orthostatic hypotension and raises the risk of cardiovascular death during heat waves and high pollution episodes. OBJECTIVE: We examined whether short-term exposures to air pollution (fine particles, ozone) and heat resulted in perturbation of arterial blood pressure (BP) in persons with type 2 diabetes mellitus (T2DM). METHODS: We conducted a panel study in 70 subjects with T2DM, measuring BP by automated oscillometric sphygmomanometer and pulse wave analysis every 2 weeks on up to five occasions (355 repeated measures). Hourly central site measurements of fine particles, ozone, and meteorology were conducted. We applied linear mixed models with random participant intercepts to investigate the association of fine particles, ozone, and ambient temperature with systolic, diastolic, and mean arterial BP in a multipollutant model, controlling for season, meteorological variables, and subject characteristics. RESULTS: An interquartile increase in ambient fine particle mass [particulate matter (PM) with an aerodynamic diameter of <= 2.5 mu m (PM2.5)] and in the traffic component black carbon in the previous 5 days (3.54 and 0.25 mu g/m(3), respectively) predicted increases of 1.4 mmHg (95% confidence interval (CI): 0.0, 2.9 mmHg] and 2.2 mmHg (95% CI: 0.4, 4.0 mmHg) in systolic BP (SBP) at the population geometric mean, respectively. In contrast, an interquartile increase in the 5-day mean of ozone (13.3 ppb) was associated with a 5.2 mmHg (95% CI: -8.6, -1.8 mmHg) decrease in SBP. Higher temperatures were associated with a marginal decrease in BP. CONCLUSIONS: In subjects with T2DM, PM was associated with increased BP, and ozone was associated with decreased BP. These effects may be clinically important in patients with already compromised autoregulatory function. C1 [Hoffmann, Barbara] Univ Dusseldorf, IUF Leibniz Res Inst Environm Med, D-40225 Dusseldorf, Germany. [Hoffmann, Barbara] Univ Dusseldorf, Fac Med, D-40225 Dusseldorf, Germany. [Hoffmann, Barbara; Luttmann-Gibson, Heike; Zanobetti, Antonella; de Souza, Celine; Foley, Christopher; Schwartz, Joel; Gold, Diane R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Cohen, Allison; Horton, Edward] Joslin Diabet Ctr, Boston, MA 02215 USA. [Suh, Helen H.] Univ Chicago, Natl Opin Res Ctr, Chicago, IL 60637 USA. [Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Mittleman, Murray; Gold, Diane R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Stone, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gold, Diane R.] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. RP Hoffmann, B (reprint author), Univ Dusseldorf, IUF Leibniz Inst Environm Med, Hennekamp 50, D-40225 Dusseldorf, Germany. EM b.hoffmann@uni-duesseldorf.de RI Wang, Linden/M-6617-2014 FU National Institutes of Health [P01 ES009825, P03 ES000002, R21ES020194]; U.S. Environmental Protection Agency [RD-83241601, RD-83479801]; Max Kade Foundation (New York, NY, USA) FX This work was supported by the National Institutes of Health (P01 ES009825, P03 ES000002, R21ES020194), the U.S. Environmental Protection Agency (RD-83241601, RD-83479801), and the Max Kade Foundation (New York, NY, USA). NR 36 TC 60 Z9 62 U1 1 U2 42 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2012 VL 120 IS 2 BP 241 EP 246 DI 10.1289/ehp.1103647 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 887GR UT WOS:000299915400028 PM 22020729 ER PT J AU Mahalingaiah, S Missmer, SA Maity, A Williams, PL Meeker, JD Berry, K Ehrlich, S Perry, MJ Cramer, DW Hauser, R AF Mahalingaiah, Shruthi Missmer, Stacey A. Maity, Arnab Williams, Paige L. Meeker, John D. Berry, Katharine Ehrlich, Shelley Perry, Melissa J. Cramer, Daniel W. Hauser, Russ TI Association of Hexachlorobenzene (HCB), Dichlorodiphenyltrichloroethane (DDT), and Dichlorodiphenyldichloroethylene (DDE) with in Vitro Fertilization (IVF) Outcomes SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE assisted reproduction; dichlorodiphenyldichloroethylene; dichlorodiphenyltrichloroethane; hexachlorobenzene; prospective cohort ID ORGANOCHLORINE PESTICIDES; INDUCED PORPHYRIA; FOLLICULAR-FLUID; ADIPOSE-TISSUE; HUMAN-MILK; SERUM DDT; WOMEN; PROGESTERONE; PREGNANCY; TOXICITY AB BACKGROUND: Hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE) are persistent chlorinated pesticides with endocrine activity that may adversely affect the early stages of human reproduction. OBJECTIVE: Our goal was to determine the association of serum levels of HCB, DDT, and DDE with implantation failure, chemical pregnancy, and spontaneous abortion in women undergoing in vitro fertilization (IVF) from 1994 to 2003. METHODS: Levels of HCB and congeners of DDT and DDE were measured in serum collected during the follicular phase. Multivariable-adjusted statistical models accommodating multiple outcomes and multiple cycles per woman were used to estimate the relation between serum pesticide levels and WE outcomes. RESULTS: A total of 720 women with a mean +/- SD age 35.4 +/- 4.2 years at enrollment contributed 774 IVF cycles. All samples had detectable levels of HCB, DDT, and DDE, with median levels of 0.087 ng/g serum for HCB, 1.12 ng/g serum for total DDT, and 1.04 ng/g serum for p,p'-DDE. Compared with the lowest quartile (Q1) of HCB, the lipid- and multivariable-adjusted odds ratio (OR) for failed implantation was significantly elevated for those with higher HCB quartiles [Q2-Q4; adjusted ORs: for Q2, 1.71; 95% confidence interval (CI): 1.03, 2.82; for Q3, 2.30; 95% CI: 1.39, 3.81; for Q4, 2.32; 95% CI: 1.38, 3.90] and showed a significantly increasing trend (p = 0.001). No statistically significant associations were observed between DDT/DDE and IVF outcomes or between HCB and chemical pregnancy or spontaneous abortion. CONCLUSIONS: Serum HCB concentrations were on average lower than that of the general U.S. population and associated with failed implantation among women undergoing IVF. C1 [Mahalingaiah, Shruthi; Missmer, Stacey A.; Berry, Katharine; Cramer, Daniel W.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Mahalingaiah, Shruthi; Missmer, Stacey A.; Berry, Katharine; Cramer, Daniel W.] Harvard Univ, Sch Med, Boston, MA USA. [Missmer, Stacey A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Missmer, Stacey A.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Maity, Arnab] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Ehrlich, Shelley; Perry, Melissa J.; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Perry, Melissa J.] George Washington Univ, Dept Environm & Occupat Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC USA. [Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. [Hauser, Russ] Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Mahalingaiah, S (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. EM smahalingaiah@partners.org RI Ehrlich , Shelley/L-6991-2015; MAITY, ARNAB/M-8142-2016; OI MAITY, ARNAB/0000-0002-3364-8933; Mahalingaiah, Shruthi/0000-0002-5527-5787; Meeker, John/0000-0001-8357-5085 FU National Institute of Environmental Health Sciences [R01-ES013967, ES000002]; National Institute of Child Health and Human Development [R01-HD32153] FX This work was supported by grants R01-ES013967 and ES000002 from the National Institute of Environmental Health Sciences and grant R01-HD32153 from the National Institute of Child Health and Human Development. NR 33 TC 11 Z9 12 U1 0 U2 12 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2012 VL 120 IS 2 BP 316 EP 320 DI 10.1289/ehp.1103696 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 887GR UT WOS:000299915400040 PM 22204795 ER PT J AU Westover, MB Cormier, J Bianchi, MT Shafi, M Kilbride, R Cole, AJ Cash, SS AF Westover, M. Brandon Cormier, Justine Bianchi, Matt T. Shafi, Mouhsin Kilbride, Ronan Cole, Andrew J. Cash, Sydney S. TI Revising the "Rule of Three" for inferring seizure freedom SO EPILEPSIA LA English DT Article DE Bayes' rule; ILAE; Epilepsy; Refractory; Statistical prediction ID EPILEPSY AB Purpose: How long after starting a new medication must a patient go without seizures before they can be regarded as seizure-free? A recent International League Against Epilepsy (ILAE) task force proposed using a Rule of Three as an operational definition of seizure freedom, according to which a patient should be considered seizure-free following an intervention after a period without seizures has elapsed equal to three times the longest preintervention interseizure interval over the previous year. This rule was motivated in large part by statistical considerations advanced in a classic 1983 paper by Hanley and Lippman-Hand. However, strict adherence to the statistical logic of this rule generally requires waiting much longer than recommended by the ILAE task force. Therefore, we set out to determine whether an alternative approach to the Rule of Three might be possible, and under what conditions the rule may be expected to hold or would need to be extended. Methods: Probabilistic modeling and application of Bayes' rule. Key Findings: We find that an alternative approach to the problem of inferring seizure freedom supports using the Rule of Three in the way proposed by the ILAE in many cases, particularly in evaluating responses to a first trial of antiseizure medication, and to favorably-selected epilepsy surgical candidates. In cases where the a priori odds of success are less favorable, our analysis requires longer seizure-free observation periods before declaring seizure freedom, up to six times the average preintervention interseizure interval. The key to our approach is to take into account not only the time elapsed without seizures but also empirical data regarding the a priori probability of achieving seizure freedom conferred by a particular intervention. Significance: In many cases it may be reasonable to consider a patient seizure-free after they have gone without seizures for a period equal to three times the preintervention interseizure interval, as proposed on pragmatic grounds in a recent ILAE position paper, although in other commonly encountered cases a waiting time up to six times this interval is required. In this work we have provided a coherent theoretical basis for modified criterion for seizure freedom, which we call the "Rule of Three-To-Six.'' C1 [Westover, M. Brandon; Cormier, Justine; Bianchi, Matt T.; Shafi, Mouhsin; Kilbride, Ronan; Cole, Andrew J.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, Boston, MA 02114 USA. [Bianchi, Matt T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. RP Westover, MB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, 55 Fruit St, Boston, MA 02114 USA. EM mwestover@partners.org FU [NINDS-NS062092] FX SSC, AJC, and MBW receive support from NINDS-NS062092. NR 12 TC 5 Z9 5 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD FEB PY 2012 VL 53 IS 2 BP 368 EP 376 DI 10.1111/j.1528-1167.2011.03355.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 882EZ UT WOS:000299546100024 PM 22191711 ER PT J AU Singh, JP Gras, D AF Singh, Jagmeet P. Gras, Daniel TI Biventricular pacing: current trends and future strategies SO EUROPEAN HEART JOURNAL LA English DT Review DE Biventricular pacing; Cardiac resynchronization therapy; Cardiomyopathy; Heart failure ID CARDIAC-RESYNCHRONIZATION THERAPY; BUNDLE-BRANCH BLOCK; HEART-FAILURE PATIENTS; LEFT-VENTRICULAR ACTIVATION; NARROW QRS COMPLEXES; DILATED CARDIOMYOPATHY; RANDOMIZED-TRIAL; LEAD PLACEMENT; MAPPING SYSTEM; MADIT-CRT AB The role of biventricular pacing is expanding beyond the New York Heart Association classes III and IV heart failure ( HF) patient to include less symptomatic patients, earlier in the course of their disease process. This multisite pacing strategy has substantially altered the natural course of ventricular failure, exerting its physiological impact through favourable cardiac remodelling and improving the ejection fraction. This has in turn resulted in long-term clinical benefits such as improved quality of life and functional capacity with a concomitant reduction in hospitalization for HF and overall mortality. Despite the successes of cardiac resynchronization therapy (CRT) and the recent expansion of its role in the treatment of HF patients, there remain some inherent limitations to the technology and its delivery. A significant minority of patients continue to remain non-responsive to this pacing strategy. This review will highlight biventricular pacing in its present form, will elaborate on strategies to enhance response to CRT, and outline future trends and synergies towards maximizing the potential benefit of this therapeutic modality. C1 [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02459 USA. [Gras, Daniel] Nouvelles Clin Nantaises, Nantes, France. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02459 USA. EM jsingh@partners.org FU Medtronic; Biotronik; St. Jude Medical; Medtronic Inc.; Boston Scientific Corp.; Guidant Corp.; Sorin Group FX D.G. received Consultancy fees from Medtronic, St Jude Medical, Biotronik and J.S. received Research grants from St. Jude Medical, Medtronic Inc., Boston Scientific Corp., and Biotronik. He is a Advisory Board/Steering Committee/Consultant in Boston Scientific Corp., St. Jude Medical, Medtronic, CardioInsight Inc., Thoratec Inc., and Biosense Webster. He also received Honoraria/Speaker fees from Medtronic Inc., Biotronik, Guidant Corp., St. Jude Medical and Sorin Group. NR 58 TC 17 Z9 18 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD FEB PY 2012 VL 33 IS 3 BP 305 EP U174 DI 10.1093/eurheartj/ehr366 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 889AO UT WOS:000300046100011 PM 21951629 ER PT J AU Lin, E McCabe, E Newton-Cheh, C Bloch, K Buys, E Wang, T Miller, KK AF Lin, Eleanor McCabe, Elizabeth Newton-Cheh, Christopher Bloch, Kenneth Buys, Emmanuel Wang, Thomas Miller, Karen K. TI Effects of transdermal testosterone on natriuretic peptide levels in women: a randomized placebo-controlled pilot study SO FERTILITY AND STERILITY LA English DT Article DE Testosterone; natriuretic peptides ID ANDROGEN-DEFICIENT WOMEN; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; HORMONE; RATS; AGE; HYPOPITUITARISM; ESTROGEN AB Objective: To investigate whether testosterone administration alters natriuretic peptide levels in women. Design: Three-month, double-blind, randomized, placebo-controlled study. Setting: Clinical research center. Patient(s): Fifty-one women with hypoandrogenemia due to hypopituitarism. Intervention(s): Transdermal testosterone (300 mg daily) or placebo patch. Main Outcome Measure(s): N-Terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Result(s): NT-proBNP levels decreased in the transdermal testosterone group compared with placebo over three months. The difference between groups remained significant after controlling for baseline age, systolic blood pressure, body mass index, and homeostasis model assessment of insulin resistance. Change in NT-proBNP over 3 months was inversely associated with change in free testosterone levels. Conclusion(s): Testosterone administration to women results in decreased natriuretic peptide levels, suggesting that testosterone may be an inverse regulator of the natriuretic peptide system. Clinical Trials Registration Number: NCT00027430. (Fertil Steril(R) 2012;97:489-93. (C) 2012 by American Society for Reproductive Medicine.) C1 [Lin, Eleanor; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [McCabe, Elizabeth; Newton-Cheh, Christopher; Bloch, Kenneth; Wang, Thomas] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA. [Bloch, Kenneth; Buys, Emmanuel] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM kkmiller@partners.org FU Food and Drug Administration [FD-R-001981]; National Institutes of Health [M01-RR-01066, T32-DK-007028-36] FX Supported by Food and Drug Administration grant FD-R-001981 and National Institutes of Health grants M01-RR-01066 and T32-DK-007028-36. Procter and Gamble Pharmaceuticals provided study medication and placebo only. NR 27 TC 1 Z9 2 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 FEB PY 2012 VL 97 IS 2 BP 489 EP 493 DI 10.1016/j.fertnstert.2011.11.001 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 887WG UT WOS:000299961800042 PM 22137497 ER PT J AU Fisher, FM Kleiner, S Douris, N Fox, EC Mepani, RJ Verdeguer, F Wu, J Kharitonenkov, A Flier, JS Maratos-Flier, E Spiegelman, BM AF Fisher, Ffolliott M. Kleiner, Sandra Douris, Nicholas Fox, Elliott C. Mepani, Rina J. Verdeguer, Francisco Wu, Jun Kharitonenkov, Alexei Flier, Jeffrey S. Maratos-Flier, Eleftheria Spiegelman, Bruce M. TI FGF21 regulates PGC-1 alpha and browning of white adipose tissues in adaptive thermogenesis SO GENES & DEVELOPMENT LA English DT Article DE FGF21; PGC-1 alpha; thermogenesis; adipose tissue ID UNCOUPLING PROTEIN-1 GENE; INSULIN SENSITIVITY; PPAR-ALPHA; RECEPTOR-ALPHA; OBESITY; ADIPOCYTES; MICE; FAT; METABOLISM; ACTIVATION AB Certain white adipose tissue (WAT) depots are readily able to convert to a "brown-like" state with prolonged cold exposure or exposure to beta-adrenergic compounds. This process is characterized by the appearance of pockets of uncoupling protein 1 (UCP1)-positive, multilocular adipocytes and serves to increase the thermogenic capacity of the organism. We show here that fibroblast growth factor 21 (FGF21) plays a physiologic role in this thermogenic recruitment of WATs. In fact, mice deficient in FGF21 display an impaired ability to adapt to chronic cold exposure, with diminished browning of WAT. Adipose-derived FGF21 acts in an autocrine/paracrine manner to increase expression of UCP1 and other thermogenic genes in fat tissues. FGF21 regulates this process, at least in part, by enhancing adipose tissue PGC-1 alpha protein levels independently of mRNA expression. We conclude that FGF21 acts to activate and expand the thermogenic machinery in vivo to provide a robust defense against hypothermia. C1 [Fisher, Ffolliott M.; Douris, Nicholas; Fox, Elliott C.; Flier, Jeffrey S.; Maratos-Flier, Eleftheria] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kleiner, Sandra; Mepani, Rina J.; Verdeguer, Francisco; Wu, Jun; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Kleiner, Sandra; Mepani, Rina J.; Verdeguer, Francisco; Wu, Jun; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst,Div Metab & Chron Dis, Boston, MA 02215 USA. [Kharitonenkov, Alexei] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Maratos-Flier, E (reprint author), Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM emaratos@bidmc.harvard.edu; bruce_spiegelman@dfci.harvard.edu FU NIH [DK31405, DK028082] FX We thank the Harvard Histology core facility for assistance in imbedding and processing fat tissue. This work was supported by NIH grants DK31405 (to B.M.S.) and DK028082 (to E.M.F.). NR 38 TC 421 Z9 430 U1 9 U2 54 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD FEB 1 PY 2012 VL 26 IS 3 BP 271 EP 281 DI 10.1101/gad.177857.111 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 890DQ UT WOS:000300125700006 PM 22302939 ER PT J AU Young, MJ Alston, TA AF Young, Mark J. Alston, Theodore A. TI Does anesthetic technique influence cancer? SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material ID RANDOMIZED-TRIAL; IMMUNE FUNCTION; NITROUS-OXIDE; BREAST-CANCER; CYTO-TOXICITY; RECURRENCE; SURGERY; MORPHINE; STRESS; ENHANCEMENT C1 [Young, Mark J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Young, MJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM talston@partners.org NR 25 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 2012 VL 24 IS 1 BP 1 EP 2 DI 10.1016/j.jclinane.2011.10.001 PG 2 WC Anesthesiology SC Anesthesiology GA 890JU UT WOS:000300141700001 PM 22154093 ER PT J AU Negi, SI Steinberg, L Polsani, VR Gowani, SA Nambi, V Kumar, V Marinescu, V Jones, PH Petersen, LA Ballantyne, CM Virani, SS AF Negi, Smita I. Steinberg, Lynne Polsani, Venkateshwar R. Gowani, Saqib A. Nambi, Vijay Kumar, Varinder Marinescu, Victor Jones, Peter H. Petersen, Laura A. Ballantyne, Christie M. Virani, Salim S. TI Non-high-density lipoprotein cholesterol calculation and goal awareness among physicians-in-training SO JOURNAL OF CLINICAL LIPIDOLOGY LA English DT Article DE Adult Treatment Panel guidelines; Non-HDL-C calculation; Non-HDL-C goals; Physicians-in-training ID SYSTEMATIC REVIEWS; IMPROVE; RISK; INTERVENTIONS; DISEASE; APOLIPOPROTEINS; ASSOCIATION; PERFORMANCE; ATTAINMENT; GUIDELINES AB BACKGROUND: Non-high density lipoprotein cholesterol (non-HDL-C) goal attainment per Adult Treatment Panel III (ATP III) guidelines remains low. OBJECTIVE: To understand gaps in knowledge and practices of physicians-in-training (internal medicine, family medicine, cardiology, endocrinology) towards non-HDL-C. METHODS: A survey based on a conceptual model to assess the trainee's knowledge, attitudes, and practice regarding non-HDL-C was developed and administered to physicians-in-training (n = 655) at 26 training programs in the United States. Responses of those in internal medicine and family medicine (residents-in-training; n = 418) were compared with those in cardiology and endocrinology (fellows-in-training; n = 124). RESULTS: Response rate was 83.7%. Fifty-three percent of residents and 31% of fellows-in-training had not read the ATP III guidelines (P < .001). Thirty-three percent of the residents and 35% fellows-in-training could not calculate non-HDL-C from a standard lipid panel (P = .7). Sixty-seven percent of the residents and 52% of fellows were not aware of treatment goals for non-HDL-C (P = .004 for comparison between residents and fellows). Both residents and fellows reported infrequent calculation of non-HDL-C levels in patients with elevated triglycerides (>= 200 mg/dL; 32.5% vs 35.4%, respectively, P = .6). Lack of familiarity with ATP 111 guidelines, lack of knowledge regarding importance of non-HDL-C, lack of institutional mandate to calculate non-HDL-C, and lack of emphasis on non-HDL-C by teaching staff were reported as barriers to non-HDL-C use in routine clinical practice. CONCLUSIONS: At least one-third of physicians-in-training could not calculate non-HDL-C from a standard lipid panel, and a large number were not aware of ATP III treatment goals pertaining to non-HDL-C. This area represents one for improvement if non-HDL-C is to be retained as a treatment target in the forthcoming ATP-IV guidelines. Published by Elsevier Inc on behalf of National Lipid Association. C1 [Negi, Smita I.; Nambi, Vijay; Jones, Peter H.; Ballantyne, Christie M.; Virani, Salim S.] Baylor Coll Med, Dept Med, Sect Atherosclerosis & Vasc Med, Houston, TX 77030 USA. [Negi, Smita I.; Nambi, Vijay; Jones, Peter H.; Ballantyne, Christie M.; Virani, Salim S.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA. [Steinberg, Lynne] Univ Houston, Houston, TX USA. [Polsani, Venkateshwar R.] Tulane Heart & Vasc Ctr, New Orleans, LA USA. [Gowani, Saqib A.] Univ Connecticut, Farmington, CT USA. [Kumar, Varinder] Univ Vermont, Burlington, VT USA. [Marinescu, Victor] William Beaumont Hosp, Detroit, MI USA. [Petersen, Laura A.; Virani, Salim S.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res, Houston, TX 77030 USA. [Petersen, Laura A.; Virani, Salim S.] Baylor Coll Med, Dev Ctr Excellence, Sect Hlth Serv, Dept Med, Houston, TX 77030 USA. RP Virani, SS (reprint author), Baylor Coll Med, Dept Med, Sect Atherosclerosis & Vasc Med, Houston, TX 77030 USA. EM virani@bcm.edu OI Steinberg, Lynne/0000-0002-3265-1778; Virani, Salim/0000-0001-9541-6954 FU Merck and Co, Inc [II SP 37267]; Department of Veterans Affairs Health Services Research and Development Service [CDA 09-028]; NIH [K23 HL096893]; Abbott; AstraZeneca; Bristol-Myers Squibb; diaDexus; GlaxoSmithKline; Kowa; Merck; Novartis; Roche; Sanofi-Synthelabo; Takeda; National Football League Medical Charities FX This work was supported by Investigator Initiated Research funding by Merck and Co, Inc (II SP 37267). Dr. Virani is supported by a Department of Veterans Affairs Health Services Research and Development Service Career Development Award (CDA 09-028). Dr. Nambi is supported by a NIH-Career Development Grant (K23 HL096893). Vijay Nambi, MD, has served on the virtual advisory board or Abbott Laboratories. Peter H. Jones, MD, is on the advisory board/consultant of Abbott, Merck, Roche/Genentech and Atherotech. Speakers Bureau for Abbott. Merck, and AstraZeneca. Christie M. Ballantyne, MD, has received grant/research support (all paid to the institution, not individual) from Abbott, AstraZeneca, Bristol-Myers Squibb, diaDexus, GlaxoSmithKline, Kowa, Merck, Novartis, Roche, Sanofi-Synthelabo, Takeda, the National Institutes of Health, American Diabetes Association, and the American Heart Association; is a consultant for Abbott, Adnexus, Amyl in. AstraZeneca, Bristol-Myers Squibb, Esperion, Genentech, GlaxoSmithKline, Idera Pharma, Kowa, Merck, Novartis, Omthera, Resverlogix, Roche, Sanofi-Synthelabo, and Takeda; on the speakers bureau for Abbott, AstraZeneca, GlaxoSmithKline, and Merck; and has received honoraria from Abbott, AstraZeneca, GlaxoSmithKline, Merck, Sanofi-Synthelabo, and Takeda. Salim S. Virani, MD, received research support (all grants to the institution and not individual) from Merck and Co, Inc., and National Football League Medical Charities and was on the speakers bureau at Abbott (discontinued 11/2010). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 27 TC 8 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-2874 EI 1876-4789 J9 J CLIN LIPIDOL JI J. Clin. Lipidol. PD FEB PY 2012 VL 6 IS 1 BP 50 EP 57 DI 10.1016/j.jacl.2011.10.020 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 886KB UT WOS:000299852200007 PM 22264574 ER PT J AU Laird, JR Katzen, BT Scheinert, D Lammer, J Carpenter, J Buchbinder, M Dave, R Ansel, G Lansky, A Cristea, E Collins, TJ Goldstein, J Cao, AY Jaff, MR AF Laird, John R. Katzen, Barry T. Scheinert, Dierk Lammer, Johannes Carpenter, Jeffrey Buchbinder, Maurice Dave, Rajesh Ansel, Gary Lansky, Alexandra Cristea, Ecaterina Collins, Tyrone J. Goldstein, Jeffrey Cao, Annie Y. Jaff, Michael R. CA RESILIENT Investigators TI Nitinol Stent Implantation vs. Balloon Angioplasty for Lesions in the Superficial Femoral and Proximal Popliteal Arteries of Patients With Claudication: Three-Year Follow-up From the RESILIENT Randomized Trial SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Article DE balloon angioplasty; stents; peripheral vascular disease; superficial femoral artery; popliteal artery; femoropopliteal segment; claudication; stenosis; outcome analysis; quality of life outcome ID OCCLUSIVE DISEASE; IN-VITRO; FRACTURE; RECANALIZATION; METAANALYSIS; PATENCY; GRAFT AB Purpose: To evaluate longer outcomes of primary nitinol stenting for the treatment of femoropopliteal lesions up to 15 cm long after these stents were found to have superior short-term patency vs. balloon angioplasty. Methods: Two hundred and six patients (143 men; mean age 67 years) with intermittent claudication due to superficial femoral and proximal popliteal artery lesions were randomized (2:1) to treatment with nitinol stents or balloon angioplasty at 24 US and European centers and followed for 3 years. In that time, 15 patients died, 20 withdrew consent, and 10 were lost to follow-up, leaving 161 (78.2%) patients for 36-month assessment. Results: The 12-month freedom from target lesion revascularization (TLR) was 87.3% for the stent group vs. 45.2% for the angioplasty group (p<0.0001). At 3 years, there was no difference in survival (90.0% vs. 91.7%, p=0.71) or major adverse events (75.2% vs. 75.2%, p=0.98) between the stent and angioplasty groups. Duplex ultrasound was not mandated after the first year, so stent patency could not be ascertained beyond 1 year, but freedom from TLR at 3 years was significantly better in the stent group (75.5% vs. 41.8%, p<0.0001), as was clinical success (63.2% vs. 17.9%, p<0.0001). At 18 months, a 4.1% (12/291) stent fracture rate was documented. Conclusion: In this multicenter trial, primary implantation of a nitinol stent for moderate-length lesions in the femoropopliteal segment of patients with claudication was associated with better long-term results vs. balloon angioplasty alone. J Endovasc Ther. 2012;19:1-9 C1 [Laird, John R.] UC Davis Hlth Syst, Sacramento, CA USA. [Buchbinder, Maurice] Scripps Clin, San Diego, CA USA. [Cao, Annie Y.] Edwards Life Sci, Irvine, CA USA. [Katzen, Barry T.] Baptist Heart & Vasc Ctr, Miami, FL USA. [Scheinert, Dierk] Leipzig Heart Ctr, Leipzig, Germany. [Lammer, Johannes] Med Univ Vienna, Vienna, Austria. [Carpenter, Jeffrey] Univ Penn, Philadelphia, PA 19104 USA. [Dave, Rajesh] Pinnacle Hlth Syst, Harrisburg, PA USA. [Ansel, Gary] Riverside Methodist Hosp, Columbus, OH 43214 USA. [Lansky, Alexandra] Yale Univ, Sch Med, New Haven, CT USA. [Cristea, Ecaterina] Cardiovasc Res Fdn, New York, NY USA. [Collins, Tyrone J.] Oschner Clin Fdn, New Orleans, LA USA. [Goldstein, Jeffrey] Prairie Educ & Res Ctr, Springfield, IL USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Laird, JR (reprint author), UC Davis Vasc Ctr, Lawrence J Ellison Ambulatory Care Ctr, 4860 Y St,Suite 3400, Sacramento, CA 95817 USA. EM john.laird@ucdmc.ucdavis.edu RI Collins, Tyrone/H-1695-2014 FU Bard Peripheral Vascular FX John R. Laird is a consultant for Bard Peripheral Vascular. Barry T. Katzen and Jeffrey Carpenter are members of the Speakers Bureau for Bard Peripheral Vascular. Alexandra Lansky and Rajesh Dave receive research support from Bard Peripheral Vascular. Gary Ansel is a member of the Speakers Bureau for Bard Peripheral Vascular and past Advisory Board Member (2005-2007) for Edwards LifeSciences. Annie Y. Cao is an employee of Edwards LifeSciences. The other authors have no commercial, proprietary, or financial interest in any products or companies described in this article. NR 26 TC 100 Z9 106 U1 0 U2 10 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD FEB PY 2012 VL 19 IS 1 BP 1 EP 9 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 889MA UT WOS:000300076600001 PM 22313193 ER PT J AU Romano, PS Volpp, K AF Romano, Patrick S. Volpp, Kevin TI The ACGME's 2011 Changes to Resident Duty Hours: Are They an Unfunded Mandate on Teaching Hospitals? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID WORK HOURS; MORTALITY; CARE; EDUCATION; IMPACT; SLEEP C1 [Romano, Patrick S.] UC Davis, Div Gen Med, Sacramento, CA 95817 USA. [Romano, Patrick S.] UC Davis, Ctr Healthcare Policy & Res, Sacramento, CA 95817 USA. [Volpp, Kevin] Univ Penn, Philadelphia Vet Affairs Med Ctr, Leonard Davis Inst Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. RP Romano, PS (reprint author), UC Davis, Div Gen Med, 4150V St,PSSB Suite 2400, Sacramento, CA 95817 USA. EM psromano@ucdavis.edu RI Romano, Patrick/N-4225-2014 OI Romano, Patrick/0000-0001-6749-3979 NR 17 TC 6 Z9 6 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2012 VL 27 IS 2 BP 136 EP 138 DI 10.1007/s11606-011-1936-x PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 889HS UT WOS:000300064900002 PM 22127799 ER PT J AU Ahalt, C Binswanger, IA Steinman, M Tulsky, J Williams, BA AF Ahalt, Cyrus Binswanger, Ingrid A. Steinman, Michael Tulsky, Jacqueline Williams, Brie A. TI Confined to Ignorance: The Absence of Prisoner Information from Nationally Representative Health Data Sets SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE incarceration; prisoner; data; health; disparities ID RISK; CARE; INCARCERATION; INMATES; DEATH; POPULATIONS; DISPARITIES; RELEASE; SYSTEM AB Incarceration is associated with poor health and high costs. Given the dramatic growth in the criminal justice system's population and associated expenses, inclusion of questions related to incarceration in national health data sets could provide essential data to researchers, clinicians and policy-makers. To evaluate a representative sample of publically available national health data sets for their ability to be used to study the health of currently or formerly incarcerated persons and to identify opportunities to improve criminal justice questions in health data sets. We reviewed the 36 data sets from the Society of General Internal Medicine Dataset Compendium related to individual health. Through content analysis using incarceration-related keywords, we identified data sets that could be used to study currently or formerly incarcerated persons, and we identified opportunities to improve the availability of relevant data. While 12 (33%) data sets returned keyword matches, none could be used to study incarcerated persons. Three (8%) could be used to study the health of formerly incarcerated individuals, but only one data set included multiple questions such as length of incarceration and age at incarceration. Missed opportunities included: (1) data sets that included current prisoners but did not record their status (10, 28%); (2) data sets that asked questions related to incarceration but did not specifically record a subject's status as formerly incarcerated (8, 22%); and (3) longitudinal studies that dropped and/or failed to record persons who became incarcerated during the study (8, 22%). Few health data sets can be used to evaluate the association between incarceration and health. Three types of changes to existing national health data sets could substantially expand the available data, including: recording incarceration status for study participants who are incarcerated; recording subjects' history of incarceration when this data is already being collected; and expanding incarceration-related questions in studies that already record incarceration history. C1 [Ahalt, Cyrus; Steinman, Michael; Williams, Brie A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Ahalt, Cyrus; Steinman, Michael; Williams, Brie A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Binswanger, Ingrid A.] Univ Colorado, Denver Sch Med, Div Gen Internal Med, Denver, CO USA. [Tulsky, Jacqueline; Williams, Brie A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Williams, BA (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. EM brie.williams@ucsf.edu OI Binswanger, Ingrid/0000-0001-8862-8078 FU National Institute of Aging [K23AG033102]; UCSF Hartford Center of Excellence; Langeloth Foundation; Robert Wood Johnson Physician Faculty Scholars Program FX Dr. Williams is supported by the National Institute of Aging (K23AG033102), the UCSF Hartford Center of Excellence, and the Langeloth Foundation. Dr. Binswanger is supported by the Robert Wood Johnson Physician Faculty Scholars Program. These funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Mr. Ahalt, Dr. Williams, and Dr. Steinman are employees of the Department of Veterans Affairs. The opinions expressed in this manuscript may not represent those of the VA. NR 39 TC 17 Z9 17 U1 3 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2012 VL 27 IS 2 BP 160 EP 166 DI 10.1007/s11606-011-1858-7 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 889HS UT WOS:000300064900009 PM 21922160 ER PT J AU Newsom, J Estrada, CA Panisko, D Willett, L AF Newsom, Jeremiah Estrada, Carlos A. Panisko, Danny Willett, Lisa TI Selecting the Best Clinical Vignettes for Academic Meetings: Should the Scoring Tool Criteria be Modified? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE professional competence; internship and residency; education medical/methods; educational measurement/methods/standards; congresses as topic; reproducibility of results ID INTERRATER AGREEMENT; STRUCTURED METHOD; ABSTRACTS; REVIEWERS; MEDICINE; AUTHORS AB The performance of scoring tools to select clinical vignettes for presentation at academic meetings has never been assessed. To measure the psychometric properties of two scoring tools used to select clinical vignettes and to determine which elements are most helpful. Prospective observational study. Participants submitting clinical vignette abstracts, Society of General Internal Medicine annual meetings (2006-2007). The 2006 scoring tool had three criteria (clarity, significance, and relevance) with brief general descriptors. The 2007 modified tool had five criteria (clarity, significance, relevance, teaching value, and overall assessment) with more detailed descriptors. A total of 938 clinical vignette abstracts were submitted (484 in 2006; 454 in 2007); 59.5% (n = 288) were accepted for presentation. Cronbach's alpha was 0.81 for the 2006 three-item tool and 0.95 for the 2007 modified five-item tool. Simplifying the five-item 2007 tool to three items (relevance, teaching value, overall assessment) yielded a Cronbach's alpha of 0.95. The agreement between the number of clinical vignettes accepted for presentation (2007) using the average score of the five items with the number that would have been accepted using the simplified three items (relevance, teaching value, overall assessment) was almost perfect, with kappa 0.89 (95% confidence interval, 0.85 to 0.93). Both scoring tools performed well, but a simplified tool with three items (relevance, teaching value, and overall assessment) and detailed descriptors was optimal; the simplified tool could improve the reviewer efficiency and quality of clinical vignettes presented at national meetings. C1 [Newsom, Jeremiah; Estrada, Carlos A.; Willett, Lisa] Univ Alabama, Birmingham, AL USA. [Newsom, Jeremiah; Estrada, Carlos A.] Vet Affairs Natl Qual Scholars Program, Birmingham VA Med Ctr, Birmingham, AL USA. [Panisko, Danny] Univ Toronto, Toronto, ON, Canada. RP Willett, L (reprint author), BDB 341,1530 3rd Ave S, Birmingham, AL 35294 USA. EM lwillett@uab.edu NR 33 TC 2 Z9 2 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2012 VL 27 IS 2 BP 202 EP 206 DI 10.1007/s11606-011-1879-2 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 889HS UT WOS:000300064900016 PM 21927965 ER PT J AU Julka, A Vranceanu, AM Shah, AS Peters, F Ring, D AF Julka, Abhishek Vranceanu, Ana-Maria Shah, Apurva S. Peters, Frank Ring, David TI Predictors of Pain During and the Day After Corticosteroid Injection for Idiopathic Trigger Finger SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Injection; pain intensity; psychosocial; trigger flare ID RANDOMIZED CONTROLLED-TRIAL; CATASTROPHIZING SCALE; STEROID INJECTION; TENNIS ELBOW; TRIAMCINOLONE; SYMPTOMS; THUMBS AB Purpose Some patients report a transient increase in pain the day after a corticosteroid injection. We investigated factors associated with greater pain during and the day after a corticosteroid injection for idiopathic trigger finger. Methods A total of 100 patients with trigger finger completed questionnaires measuring heightened illness concern, catastrophic thinking, depression, perceived health, expected pain, pain with injection, and pain the day after injection. We performed bivariate analysis to determine variables associated with pain with injection, next-day pain, and next-day pain greater than 4 points on an 11-point ordinal scale. We entered variables with a significant correlation into multivariable linear regression models. Results The average pain with injection and the day after injection were 4.3 (SD 2.8) and 1.8 (SD 2.0), respectively. Expected pain, heightened illness concern, catastrophic thinking, depression, physician, and gender correlated with pain with injection. A multivariable regression model conducted in backward stepwise fashion demonstrated that physician, depression, expected pain, and female gender explained 28% of the variance in pain with injection. Pain with injection was the only significant predictor of next-day pain and pain greater than 4 points the day after injection. Conclusions Our data suggest that psychosocial factors are the strongest correlates of pain with corticosteroid injection, but a large portion of the variability remains unexplained. Future research will investigate cognitive/behavioral methods for decreasing pain with injection. (J Hand Surg 2012;37A:237-242. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Behav Med, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 22 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD FEB PY 2012 VL 37A IS 2 BP 237 EP 242 DI 10.1016/j.jhsa.2011.10.055 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 889JK UT WOS:000300069800005 PM 22192164 ER PT J AU Buijze, GA Wijffels, MME Guitton, TG Grewal, R van Dijk, CN Ring, D AF Buijze, Geert A. Wijffels, Mathieu M. E. Guitton, Thierry G. Grewal, Ruby van Dijk, C. Niek Ring, David CA Sci Variation Grp TI Interobserver Reliability of Computed Tomography to Diagnose Scaphoid Waist Fracture Union SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Interobserver reliability; scaphoid fracture; union; CT; diagnosis ID OBSERVER AGREEMENT; RADIOGRAPHY; SIGNS AB Purpose To determine the interobserver agreement and diagnostic performance characteristics of computed tomography (CT) for determining union of scaphoid waist fractures. Methods A total of 59 orthopedic and trauma surgeons rated for union a set of 30 sagittal CT scans of 30 scaphoid waist fractures. Of these fractures, 20 were treated nonoperatively, were imaged between 6 and 10 weeks after injury, and were known to have eventually achieved union. Ten were operatively confirmed to be ununited. We rated each scan as united or ununited using a Web-based rating application. We assessed interobserver reliability using Siegel's multirater Kappa. We calculated diagnostic performance characteristics using Bayesian formulas. Results The interobserver agreement among 59 raters was substantial. The average sensitivity, specificity, and accuracy of diagnosing union of scaphoid waist fractures on sagittal CT scans were 78%, 96%, and 84%, respectively. Assuming a 90% prevalence of fracture union of the scaphoid, the positive predictive value of a diagnosis of union on sagittal CT scan was 0.99 and the negative predictive value was 0.41. Conclusions Our results suggest that CT scans are accurate and reliable for diagnosis of union but inadequate for ruling out nonunion of scaphoid waist fractures between 6 and 10 weeks after injury. (J Hand Surg 2012;37A:250-254. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Hand & Upper Extrem Serv, 55 Fruit St,YAW 2, Boston, MA 02114 USA. EM dring@partners.org RI Page, Richard/K-6327-2015; OI Page, Richard/0000-0002-2225-7144; Guitton, Thierry/0000-0002-2599-1985 FU Netherlands Organization for Scientific Research (NWO) FX G.A.B. thanks the Netherlands Organization for Scientific Research (NWO) for their support. NR 17 TC 13 Z9 13 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD FEB PY 2012 VL 37A IS 2 BP 250 EP 254 DI 10.1016/j.jhsa.2011.10.051 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 889JK UT WOS:000300069800007 PM 22281168 ER PT J AU Isaac, T Zheng, J Jha, A AF Isaac, Thomas Zheng, Jie Jha, Ashish TI Use of UpToDate and outcomes in US hospitals SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID CLINICAL QUESTIONS; CLAIMS DATA; PATIENT-CARE; ASSOCIATION; QUALITY; EFFICIENCY; OBSTACLES; DATABASE; ANSWER; IMPACT AB BACKGROUND: Computerized clinical knowledge mana-gement systems hold enormous potential for improving quality and efficiency. However, their impact on clinical practice is not well known. OBJECTIVE: To examine the impact of UpToDate on outcomes of care. DESIGN: Retrospective study. SETTING: National sample of US inpatient hospitals. PATIENTS: Fee-for-service Medicare beneficiaries. INTERVENTION: Adoption of UpToDate in US hospitals. MEASUREMENT: Risk-adjusted lengths of stay, mortality rates, and quality performance. RESULTS: We found that patients admitted to hospitals using UpToDate had shorter lengths of stay than patients admitted to non-UpToDate hospitals overall (5.6 days vs 5.7 days; P < 0.001) and among 6 prespecified conditions (range, -0.1 to -0.3 days; P < 0.001 for each). Further, patients admitted to UpToDate hospitals had lower riskadjusted mortality rate for 3 of the 6 conditions (range, -0.1% to -0.6% mortality reduction; P < 0.05). Finally, hospitals with UpToDate had better quality performance for every condition on the Hospital Quality Alliance metrics. In subgroup analyses, we found that it was the smaller hospitals and the non-teaching hospitals where the benefits of the UpToDate seemed most pronounced, compared to the larger, teaching institutions where the benefits of UpToDate seemed small or nonexistent. CONCLUSIONS: We found a very small but consistent association between use of UpToDate and reduced length of stay, lower risk-adjusted mortality rates, and better quality performance, at least in the smaller, non-teaching institutions. These findings may suggest that computerized tools such as UpToDate could be helpful in improving care. Journal of Hospital Medicine 2012; 7: 85-90 (C) 2011 Society of Hospital Medicine C1 [Zheng, Jie; Jha, Ashish] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Isaac, Thomas] Beth Israel Deaconess Med Ctr, Div Gen Internal Med & Primary Care, Boston, MA 02215 USA. [Jha, Ashish] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Jha, Ashish] VA Boston Healthcare Syst, Boston, MA USA. RP Jha, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu FU UpToDate, Inc. FX This study was funded by UpToDate, Inc. The funder had no role in study design, input into analyses presented, drafting or editing the manuscript, nor saw the manuscript prior to submission. NR 25 TC 28 Z9 30 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD FEB PY 2012 VL 7 IS 2 BP 85 EP 90 DI 10.1002/jhm.944 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 887SC UT WOS:000299948800004 PM 22095750 ER PT J AU Prabaker, KK Tran, TPH Pratummas, T Goetz, MB Graber, CJ AF Prabaker, Kavitha K. Tran, Thuong P. -H. Pratummas, Tamara Goetz, Matthew Bidwell Graber, Christopher J. TI Elevated vancomycin trough is not associated with nephrotoxicity among inpatient veterans SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE contrast; nephrotoxicity; reversible; vancomycin ID RESISTANT STAPHYLOCOCCUS-AUREUS; INDUCED NEPHROPATHY; N-ACETYLCYSTEINE; THERAPY; AMINOGLYCOSIDE; BACTEREMIA; TOXICITY; INFECTIONS; PATHOGENESIS; COMBINATION AB BACKGROUND: Vancomycin troughs of 15-20 mg/L are recommended in the treatment of invasive staphylococcal disease, higher levels than previously recommended. OBJECTIVE/SETTING: We sought to determine if there was an association between vancomycin trough and nephrotoxicity, defined as 0.5 mg/L or 50% increase in serum creatinine, at a large Veterans Affairs medical center. PATIENTS AND METHODS: We reviewed records of 348 inpatients at our institution who received >= 5 days of vancomycin during 2 time periods when vancomycin dosing protocols differed (May 2005-April 2006 and January 2007December 2007). Potential risk factors for nephrotoxicity were collected prior to nephrotoxicity onset, and all patients with nephrotoxicity events occurring within 5 days of starting vancomycin were excluded. RESULTS: Overall incidence of nephrotoxicity was 31/348 patients (8.9%). A similar percentage of patients experienced nephrotoxicity in 2005-2006 versus 2007 (16/201 vs 15/147, respectively; P = 0.57), despite a rise in mean (9.7 mg/L in 2005-2006 vs 13.2 mg/L in 2007; P < 0.0001) and highest (11.8 mg/L in 2005-2006 vs 15.7 mg/L in 2007; P < 0.0001) vancomycin trough levels achieved. In a multivariate logistic regression model, only receipt of intravenous contrast dye was significantly associated with nephrotoxicity (OR 4.01, P < 0.001), though there was a trend toward an association between maximum vancomycin trough >= 15 mg/L and nephrotoxicity (OR 2.05, P = 0.082). Overall reversibility of nephrotoxicity either prior to or within 72 hours of vancomycin discontinuation was 77.8%. CONCLUSIONS: We conclude that nephrotoxicity, with higher trough levels occurring at >= 5 days of vancomycin therapy, was uncommon at our institution and typically reversible. Journal of Hospital Medicine 2012; 7: 91-97. (C) 2011 Society of Hospital Medicine C1 [Tran, Thuong P. -H.; Goetz, Matthew Bidwell; Graber, Christopher J.] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA 90073 USA. [Prabaker, Kavitha K.; Goetz, Matthew Bidwell; Graber, Christopher J.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Prabaker, Kavitha K.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Tran, Thuong P. -H.; Pratummas, Tamara] VA Greater Los Angeles Healthcare Syst, Serv Pharm, Los Angeles, CA 90073 USA. [Goetz, Matthew Bidwell; Graber, Christopher J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Graber, CJ (reprint author), VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, 11301 Wilshire Blvd,111-F, Los Angeles, CA 90073 USA. EM cgraber@ucla.edu OI Goetz, Matthew/0000-0003-4542-992X FU Ortho-McNeil-Janssen; Merck FX All authors report no conflicts of interest relevant to the content of the article, though C.J.G. has received an unrestricted educational grant from Ortho-McNeil-Janssen, grant support for an unrelated project from Merck, and has served on an advisory board for Pfizer. This project was not supported by extramural funding. NR 41 TC 14 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD FEB PY 2012 VL 7 IS 2 BP 91 EP 97 DI 10.1002/jhm.946 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 887SC UT WOS:000299948800005 PM 22086511 ER PT J AU Perkins, HS Cortez, JD Hazuda, HP AF Perkins, Henry S. Cortez, Josie D. Hazuda, Helen P. TI Patients' diverse beliefs about what happens at the time of death SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID LIFE DECISION-MAKING; MEDICAL PROCEDURES; CULTURAL ISSUES; CANCER-PATIENTS; END; CARE; INFORMATION; STRATEGIES AB BACKGROUND: Beliefs about what happens at the time of death surely affect a patient's whole dying experience and could help guide end-of-life care. Yet virtually no research describes those beliefs. This exploratory study begins the descriptive process. METHODS: Assuming culture is key, we interviewed 26 Mexican-American (MA), 18 Euro-American (EA), and 14 African-American (AA) inpatients about their beliefs concerning what happens at the time of death. RESULTS: One belief, that death separates the dead from the living, was widespread. Majorities of all 3 ethnic group samples and of 5 of the 6 gender subsamples expressed this belief, saying the dead "go" or "leave" from this life. Other beliefs differed by ethnic group or gender. For example, more EAs (50%) than others said death is a momentary event, and more MAs (35%) than others said death involves "being taken" by an external force (always God or Jesus). Furthermore, considerably more EA women (45%) than others said some senses persist after death. In contrast, the physiologic signs that participants cited as defining the exact time of death varied from individual to individual with no ethnic or gender pattern, and no one sign predominated. CONCLUSIONS: A few beliefs about what happens at the time of death may characterize Americans in general; many other beliefs may characterize only certain ethnic groups, genders, or individuals. To identify such beliefs and to use them to guide end-of-life care, hospitalists and other health professionals may have to elicit them directly from patients or survivors. Journal of Hospital Medicine 2012; 7: 110-116. (C) 2011 Society of Hospital Medicine C1 [Perkins, Henry S.; Hazuda, Helen P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Cortez, Josie D.] Intercultural Dev Res Assoc, San Antonio, TX USA. [Hazuda, Helen P.] Audie L Murphy Mem Vet Adm Med Ctr, Dept Vet Affairs, San Antonio, TX 78284 USA. RP Perkins, HS (reprint author), Univ Texas Hlth Sci Ctr, Dept Med, Div Gen Med, POB 1696, Dearborn, MI 48121 USA. EM perkins@uthscsa.edu FU Audie L. Murphy Veterans Administration Medical Center, San Antonio, Texas; Department of Veterans Affairs; John A. Hartford Foundation; American Federation on Aging Research; Mexican-American Medical Treatment Effectiveness Research Center; Aging Research and Education Center; Medical Dean's Office; University of Texas Health Science Center at San Antonio FX This work was supported with resources from the Audie L. Murphy Veterans Administration Medical Center, San Antonio, Texas, but the views expressed here do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government.; The following institutions helped fund the research either directly or indirectly: The Department of Veterans Affairs; The John A. Hartford Foundation; the American Federation on Aging Research; and the Mexican-American Medical Treatment Effectiveness Research Center, the Aging Research and Education Center, and the Medical Dean's Office, all at The University of Texas Health Science Center at San Antonio. Funders played no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, and approval of the manuscript. The authors have no financial conflict of interests. NR 28 TC 1 Z9 1 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD FEB PY 2012 VL 7 IS 2 BP 110 EP 116 DI 10.1002/jhm.947 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 887SC UT WOS:000299948800008 PM 22125098 ER PT J AU Kansagara, D Ramsay, RS Labby, D Saha, S AF Kansagara, Devan Ramsay, Rebecca S. Labby, David Saha, Somnath TI Post-discharge intervention in vulnerable, chronically ill patients SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE communication; continuity of care; quality improvement; transition and discharge planning ID CONGESTIVE-HEART-FAILURE; RANDOMIZED CONTROLLED-TRIAL; TYPE-2 DIABETES-MELLITUS; HOME-BASED INTERVENTION; PRIMARY-CARE; SELF-MANAGEMENT; HOSPITAL DISCHARGE; CHRONIC ILLNESS; FOLLOW-UP; ELDERLY-PATIENTS AB BACKGROUND: Studies suggest that the inpatient to outpatient transition of care is a vulnerable period for patients, and socioeconomically disadvantaged populations may be particularly susceptible. OBJECTIVE: In this prospective cohort study, clustered by hospital, we sought to determine the feasibility and utility of a simple, post-discharge intervention in reducing hospital readmissions. METHODS: Chronically ill Medicaid managed care members were consecutively identified from the discharge records of 10 area hospitals. For patients from the 7 intervention hospitals, trained medical assistants performed a brief telephone needs assessment, within 1 week of discharge, in which issues requiring near-term resolution were identified and addressed. Patients with more complicated care needs were identified according to a 4domain care needs framework and enrolled in more intensive care management. Patients discharged from the 3 control hospitals received usual care. We used a generalized estimating equation model, which adjusts for clustering by hospital, to evaluate the primary outcome of hospital readmission within 60 days. RESULTS: There were 97 intervention and 130 control patients. Intervention patients were slightly younger and had higher adjusted clinical group (ACG) scores. In unadjusted analysis, the intervention group had lower, but statistically similar, 60-day rehospitalization rates (23.7% vs 29.2%, P =0.35). This difference became significant after controlling for ACG score, prior inpatient utilization, and age: adjusted odds ratio (OR) [95% confidence interval (CI)] 0.49 [0.24-1.00]. CONCLUSIONS: A simple post-discharge intervention and needs assessment may be associated with reduced recurrent hospitalization rates in a cohort of chronically ill Medicaid managed care patients with diverse care needs. Journal of Hospital Medicine 2012; 7: 124-130. (C) 2011 Society of Hospital Medicine C1 [Kansagara, Devan] Oregon Hlth & Sci Univ, Med P3, Portland VA Med Ctr, Portland, OR 97239 USA. [Ramsay, Rebecca S.; Labby, David] CareOregon, Portland, OR USA. RP Kansagara, D (reprint author), Oregon Hlth & Sci Univ, Med P3, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM kansagar@ohsu.edu FU Medical Research Foundation; Oregon Health and Science University; United States Department of Veterans Affairs FX This work was supported by a grant from the Medical Research Foundation and with help from the Human Investigations Program at Oregon Health and Science University. Drs Kansagara and Saha were additionally supported by the United States Department of Veterans Affairs. The sponsors played no role in study design; collection, analysis, and interpretation of data; writing of the report; or the decision to submit the paper for publication. None of the authors has a relevant conflict of interest. NR 41 TC 9 Z9 9 U1 3 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD FEB PY 2012 VL 7 IS 2 BP 124 EP 130 DI 10.1002/jhm.941 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 887SC UT WOS:000299948800010 PM 22086871 ER PT J AU Schmid, DA Yang, T Ogier, M Adams, I Mirakhur, Y Wang, QF Massa, SM Longo, FM Katz, DM AF Schmid, Danielle A. Yang, Tao Ogier, Michael Adams, Ian Mirakhur, Yatin Wang, Qifang Massa, Stephen M. Longo, Frank M. Katz, David M. TI A TrkB Small Molecule Partial Agonist Rescues TrkB Phosphorylation Deficits and Improves Respiratory Function in a Mouse Model of Rett Syndrome SO JOURNAL OF NEUROSCIENCE LA English DT Article ID POTENT NEUROTROPHIC ACTIVITIES; CPG-BINDING PROTEIN-2; KOLLIKER-FUSE NUCLEUS; FACTOR EXPRESSION; MECP2-NULL MICE; LIFE-SPAN; RECEPTORS; DISORDERS; DYSFUNCTION; NEURONS AB Rett syndrome (RTT) results from loss-of-function mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2) and is characterized by abnormal motor, respiratory and autonomic control, cognitive impairment, autistic-like behaviors and increased risk of seizures. RTT patients and Mecp2-null mice exhibit reduced expression of brain-derived neurotrophic factor (BDNF), which has been linked in mice to increased respiratory frequency, a hallmark of RTT. The present study was undertaken to test the hypotheses that BDNF deficits in Mecp2 mutants are associated with reduced activation of the BDNF receptor, TrkB, and that pharmacologic activation of TrkB would improve respiratory function. We characterized BDNF protein expression, TrkB activation and respiration in heterozygous female Mecp2 mutant mice (Het), a model that recapitulates the somatic mosaicism for mutant MECP2 found in typical RTT patients, and evaluated the ability of a small molecule TrkB agonist, LM22A-4, to ameliorate biochemical and functional abnormalities in these animals. We found that Het mice exhibit (1) reduced BDNF expression and TrkB activation in the medulla and pons and (2) breathing dysfunction, characterized by increased frequency due to periods of tachypnea, and increased apneas, as in RTT patients. Treatment of Het mice with LM22A-4 for 4 weeks rescued wild-type levels of TrkB phosphorylation in the medulla and pons and restored wild-type breathing frequency. These data provide new insight into the role of BDNF signaling deficits in the pathophysiology of RTT and highlight TrkB as a possible therapeutic target in this disease. C1 [Schmid, Danielle A.; Ogier, Michael; Adams, Ian; Mirakhur, Yatin; Wang, Qifang; Katz, David M.] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. [Yang, Tao; Longo, Frank M.] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Massa, Stephen M.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Neurol, San Francisco, CA 94121 USA. [Massa, Stephen M.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Lab Computat Neurochem & Drug Discovery, San Francisco, CA 94121 USA. [Massa, Stephen M.] Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. RP Katz, DM (reprint author), Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. EM david.katz@case.edu FU National Institute of Neurological Disorders and Stroke; American Recovery and Reinvestment Act; International Rett Syndrome Foundation; Jean Perkins Foundation; Taube Philanthropies; Koret Foundation; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory RD FX This work was supported by the National Institute of Neurological Disorders and Stroke, including funding from the American Recovery and Reinvestment Act (D.M.K.), the International Rett Syndrome Foundation (D.M.K.), the Jean Perkins Foundation (F.M.L.), Taube Philanthropies (F.M.L.), the Koret Foundation (F.M.L.), the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory R&D (S.M.M.). We thank James Howell, and Elizabeth Shick for outstanding technical assistance, Dr. David Baekey (University of Florida) for validating the selection of quiet breathing periods used for analysis of the plethysmographic results, and Drs. Sharyl Fyffe-Maricich and Steve Maricich for their thoughtful comments on an earlier version of the manuscript. NR 40 TC 53 Z9 53 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 FEB 1 PY 2012 VL 32 IS 5 BP 1803 EP 1810 DI 10.1523/JNEUROSCI.0865-11.2012 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 888AW UT WOS:000299977200026 PM 22302819 ER PT J AU Buckley, PC Seldin, EB Dodson, TB August, M AF Buckley, Panasaya Charenkavanich Seldin, Edward B. Dodson, Thomas B. August, Meredith TI Multilocularity as a Radiographic Marker of the Keratocystic Odontogenic Tumor SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article AB Purpose: The purpose of this study was to answer this clinical question: When a patient presents with a radiolucent lesion of the mandible presumed to be an odontogenic cystic lesion, to what extent is the radiographic finding of multilocularity predictive of a final diagnosis of keratocystic odontogenic tumor (KCOT)? Materials and Methods: The study sample was derived from the population of patients who presented to the Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital for evaluation and management of suspected mandibular lesions from January 1991 through January 2009. Subjects were eligible for study inclusion if there was a final histologic diagnosis of KCOT or dentigerous cyst. The predictor variable was radiographic appearance of the lesion and was grouped into 2 categories (unilocular or multilocular). The outcome variable was lesion type (KCOT or dentigerous cyst). Appropriate univariate, bivariate, and multivariate statistics were computed. Statistical significance was defined as P < .05. Results: The study consisted of 130 subjects. Multilocular lesions were 1.7 times more likely to be KCOTs than unilocular lesions (P = .0001). The sensitivity, specificity, and positive and negative predictive values were 0.48, 0.87, 0.86, and 0.49, respectively. In the multiple logistic regression model, a multilocular radiographic appearance was associated with a 12-fold (95% confidence interval, 3.7 to 38) increased risk of KCOT. Conclusion: The results of this study confirm the hypothesis that radiographic multilocularity is predictive of a KCOT because it is associated with a 12-fold increased risk for the diagnosis of KCOT. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:320-324, 2012 C1 [Buckley, Panasaya Charenkavanich] Harvard Univ, Sch Dent Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP August, M (reprint author), Harvard Univ, Sch Dent Med, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM maugust@partners.org FU Harvard Medical School/Harvard School of Dental Medicine Office of Enrichment; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education; Massachusetts General Physicians Organization FX This work was supported by Harvard Medical School/Harvard School of Dental Medicine Office of Enrichment Programs, Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund, and Massachusetts General Physicians Organization. NR 12 TC 2 Z9 5 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2012 VL 70 IS 2 BP 320 EP 324 DI 10.1016/j.joms.2011.03.012 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 889DO UT WOS:000300053900020 PM 21778016 ER PT J AU Goldwaser, BR Papadaki, ME Kaban, LB Troulis, MJ AF Goldwaser, Batya R. Papadaki, Maria E. Kaban, Leonard B. Troulis, Maria J. TI Automated Continuous Mandibular Distraction Osteogenesis: Review of the Literature SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Review ID GRADUAL DISTRACTION; BONE DISTRACTION; DEVICE; FREQUENCY; REGENERATION; MINIPIGS; FORCES; SHEEP AB Purpose: Current devices for mandibular distraction osteogenesis ( DO) are complex and require significant patient or family skill during active distraction. Successful development of an automated, continuous distraction device would eliminate the need for patient participation in this process. The purpose of this study was to comprehensively review devices currently in development for continuous DO and to identify and evaluate the achieved successes and remaining problems. Materials and Methods: A PubMed search of the English language literature in October 2008 using the keywords automatic or automated or continuous or hydraulic or motor or magnetic or spring and distraction osteogenesis was performed. The search included all technical notes, animal studies, and human studies describing the use of any automated continuous distraction device for the mandible. Excluded were studies using distraction devices employing hydraulics, motors, or springs that did not distract automatically and continuously and devices used for bones other than the mandible. Results: The search returned 97 matches. Of these, 12 articles were selected as relevant to this review based on the inclusion and exclusion criteria detailed above. Eight distinct devices for automated, continuous DO were described in these reports and evaluated in this review. These included motor-driven, spring-mediated, and hydraulically powered distractors. Conclusions: The abundance of research currently underway to develop a continuous distractor highlights the clinical demand for, and usefulness, of such a device. Despite many advances and promising results, significant problems remain to be overcome before any of these devices gain widespread clinical acceptance. (C) 2012 Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70: 407-416, 2012 C1 [Troulis, Maria J.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg,Residency Training, Boston, MA 02114 USA. RP Troulis, MJ (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg,Residency Training, 55 Fruit ST, Boston, MA 02114 USA. EM Mtroulis@partners.org FU Hanson Foundation (Boston, MA); Massachusetts General Hospital; OMFS; NIH SBIR [5R44 DE 014803-03] FX This study was funded in part by the Hanson Foundation (Boston, MA), the Massachusetts General Hospital, OMFS Education/Research Fund, and the NIH SBIR Grant (5R44 DE 014803-03). NR 33 TC 8 Z9 8 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2012 VL 70 IS 2 BP 407 EP 416 DI 10.1016/j.joms.2011.01.042 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 889DO UT WOS:000300053900035 PM 21676514 ER PT J AU Kossida, T Rigopoulos, D Katsambas, A Anderson, RR AF Kossida, Theodora Rigopoulos, Dimitrios Katsambas, Andreas Anderson, R. Rox TI Optimal tattoo removal in a single laser session based on the method of repeated exposures SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE efficacy; laser; multiple exposure; Q-switched; removal; tattoo ID SWITCHED RUBY-LASER; MICROSCOPIC ANALYSIS; PICOSECOND; NM; PIGMENT; LIGHT; MODEL AB Background: Unwanted tattoos are treated with Q-switched lasers. Despite a series of treatments, efficacy is limited. Objective: We compared a single Q-switched laser treatment pass with 4 treatment passes separated by 20 minutes. Methods: Eighteen tattoos on 12 adults were divided in half and randomized. One half received a single treatment pass (the "conventional" method) with a Q-switched alexandrite laser (5.5 J/cm(2), 755 nm, 100-nanosecond pulse duration, 3-mm spot size), and the other half received 4 treatment passes with an interval of 20 minutes between passes (the "R20" method). Tattoo lightening was compared 3 months later, by blinded evaluation of photographs. Biopsy specimens obtained before and immediately after treatment on both halves were also compared in blinded fashion. Results: Immediate whitening reaction occurred on the first treatment pass, with little or no whitening on subsequent passes. Three months later, treatment with the R20 method was much more effective than conventional single-pass laser treatment (P <.01; all tattoos favored the R20 method). Despite greater epidermal injury with the R20 method, neither method caused adverse events or scarring. Light microscopy showed greater dispersion of tattoo ink with the R20 method. Limitations: This prospective study involved a small number of subjects. Conclusions: The R20 method is much more effective than conventional laser tattoo treatment, removing most tattoos in a single treatment session. New laser device technology is not required to practice this method. (J Am Acad Dermatol 2012;66:271-7.) C1 [Kossida, Theodora; Rigopoulos, Dimitrios; Katsambas, Andreas] Univ Athens, Sch Med, Dept Dermatol 1, Andreas Sygros Hosp, Athens 11528, Greece. [Anderson, R. Rox] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp,Wellman Ctr Photomed, Boston, MA 02115 USA. RP Kossida, T (reprint author), 5 I Dragoumi St, Athens 16121, Greece. EM thkossida@gmail.com FU Greek Ministry of National Education and Religious Affairs; Operational Programme for Education and Initial Vocational Training (O.P. "Education," Hrakleitos programme); European Regional Development Fund (ERDF); European Social Fund (ESF) FX Greek Ministry of National Education and Religious Affairs, Operational Programme for Education and Initial Vocational Training (O.P. "Education," Hrakleitos programme); co-funded by the 3rd Community Structural Funds, namely the European Regional Development Fund (ERDF) and the European Social Fund (ESF). NR 20 TC 27 Z9 29 U1 0 U2 13 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2012 VL 66 IS 2 BP 271 EP 277 DI 10.1016/j.jaad.2011.07.024 PG 7 WC Dermatology SC Dermatology GA 888UW UT WOS:000300031100011 PM 22036610 ER PT J AU Strang, BL Boulant, S Chang, L Knipe, DM Kirchhausen, T Coen, DM AF Strang, Blair L. Boulant, Steeve Chang, Lynne Knipe, David M. Kirchhausen, Tomas Coen, Donald M. TI Human Cytomegalovirus UL44 Concentrates at the Periphery of Replication Compartments, the Site of Viral DNA Synthesis SO JOURNAL OF VIROLOGY LA English DT Article ID SIMPLEX-VIRUS TYPE-1; LATE GENE-EXPRESSION; ACCESSORY SUBUNIT UL44; BINDING-PROTEIN; INFECTED-CELLS; LATE PROMOTER; LOCALIZATION; POLYMERASE; ASSOCIATION; IDENTIFICATION AB The formation of replication compartments, the subnuclear structures in which the viral DNA genome is replicated, is a hallmark of hapesvirus infections. The localization of proteins and viral DNA within human cytomegalovirus replication compartments is not well characterized. Immunofluorescence analysis demonstrated the accumulation of the viral DNA polymerase subunit UL44 at the periphery of replication compartments and the presence of different populations of UL44 in infected cells. In contrast, the viral single-stranded-DNA binding protein UL57 was distributed throughout replication compartments. Using "click chemistry" to detect 5-ethyny1-2'-deoxyuridine (EdU) incorporation into replicating viral DNA and pulse-chase protocols, we found that viral DNA synthesis occurs at the periphery of replication compartments and that replicated viral DNA subsequently localizes to the interior of replication compartments. The interiors of replication compartments also contain regions in which UL44 and EdU-labeled DNA are absent. The treatment of cells with a viral DNA polymerase inhibitor reversibly caused the dispersal of both 1JL44 and EdU-labeled viral DNA from replication compartments, indicating that ongoing viral DNA synthesis is necessary to maintain the organization of replication compartments. Our results reveal a previously unappreciated complexity of the organization of human cytomegalovirus replication compartments. C1 [Strang, Blair L.; Coen, Donald M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Boulant, Steeve; Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Immune Dis Inst, Boston, MA 02115 USA. [Boulant, Steeve; Kirchhausen, Tomas] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp, Boston, MA 02115 USA. [Chang, Lynne; Knipe, David M.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. RP Coen, DM (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM don_coen@hms.harvard.edu FU NIH [AI19838, AI26077, AI06106, GM 075252]; New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease, Core Imaging Facility [AI057159] FX This work was supported by NIH grants AI19838 and AI26077 to D.M.C., NIH grant AI06106 to D.M.K., and grants GM 075252 (NIH) and U54 AI057159 (New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease, Core Imaging Facility) to T.K. NR 31 TC 15 Z9 15 U1 0 U2 2 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 FEB PY 2012 VL 86 IS 4 BP 2089 EP 2095 DI 10.1128/JVI.06720-11 PG 7 WC Virology SC Virology GA 886OA UT WOS:000299862500018 PM 22156516 ER PT J AU Lavine, CL Lao, S Montefiori, DC Haynes, BF Sodroski, JG Yang, XZ AF Lavine, Christy L. Lao, Socheata Montefiori, David C. Haynes, Barton F. Sodroski, Joseph G. Yang, Xinzhen CA NIAID Ctr HIV AIDS Vaccine Immunol TI High-Mannose Glycan-Dependent Epitopes Are Frequently Targeted in Broad Neutralizing Antibody Responses during Human Immunodeficiency Virus Type 1 Infection SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; GP120 ENVELOPE GLYCOPROTEIN; HIV-1 GP120; OLIGOSACCHARIDE STRUCTURES; EFFICIENT NEUTRALIZATION; LINKED OLIGOSACCHARIDES; DC-SIGN; 2G12; COMPLEX; CD4 AB Broad and potent neutralizing antibody (BNAb) responses are rare in people infected by human immunodeficiency virus type 1 (HIV-1). Clearly defining the nature of BNAb epitopes on HIV-1 envelope glycoproteins (Envs) targeted in vivo is critical for future directions of anti-HIV-1 vaccine development. Conventional techniques are successful in defining neutralizing epitopes in a small number of individual subjects but fail in studying large groups of subjects. Two independent methods were employed to investigate the nature of NAb epitopes targeted in 9 subjects, identified by the MAID Center for EUV/AIDS Vaccine Immunology (CHAVI) 001 and 008 clinical teams, known to make a strong BNAb response. Neutralizing activity from 8/9 subjects was enhanced by enriching high-mannose N-linked glycan (HM-glycan) of HIV-1 glycoproteins on neutralization target viruses and was sensitive to specific glycan deletion mutations of HIV-1 glycoproteins, indicating that HM-glycan-dependent epitopes are targeted by BNAb responses in these subjects. This discovery adds to accumulating evidence supporting the hypothesis that glycans are important targets on HIV-1 glycoproteins for BNAb responses in vivo, providing an important lead for future directions in developing NAb-based anti-HIV-1 vaccines. C1 [Lavine, Christy L.; Lao, Socheata; Yang, Xinzhen] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis,Dept Med, Boston, MA 02114 USA. [Montefiori, David C.; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Sodroski, Joseph G.] Harvard Univ, Sch Med, Dept Canc Immunol, Boston, MA USA. [Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. RP Yang, XZ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis,Dept Med, Boston, MA 02114 USA. EM xyang1@bidmc.harvard.edu FU NIAID Center for HIV/AIDS Vaccine Immunology [AI067854]; NIH [RO1 AI073133] FX This work was supported by the NIAID Center for HIV/AIDS Vaccine Immunology (grant AI067854) and by a grant (RO1 AI073133) from the NIH to X.Y. NR 65 TC 29 Z9 29 U1 1 U2 18 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 FEB PY 2012 VL 86 IS 4 BP 2153 EP 2164 DI 10.1128/JVI.06201-11 PG 12 WC Virology SC Virology GA 886OA UT WOS:000299862500024 PM 22156525 ER PT J AU Konry, T Bale, SS Bhushan, A Shen, K Seker, E Polyak, B Yarmush, M AF Konry, Tania Bale, Shyam Sundhar Bhushan, Abhinav Shen, Keyue Seker, Erkin Polyak, Boris Yarmush, Martin TI Particles and microfluidics merged: perspectives of highly sensitive diagnostic detection SO MICROCHIMICA ACTA LA English DT Review DE Diagnostic detection; Particle technologies; Microfluidic; Biomarker research; Cancer diagnosis; Detection of infectious microorganisms; Bead based diagnostics ID ON-A-CHIP; MINIATURIZED TOTAL ANALYSIS; CHEMICAL-ANALYSIS SYSTEMS; POLYMERASE-CHAIN-REACTION; SINGLE CELLS; REAL-TIME; ANTIFERROMAGNETIC NANOPARTICLES; MEDICAL DIAGNOSTICS; PICOLITER DROPLETS; PROTEIN-ANALYSIS AB There is a growing need for diagnostic technologies that provide laboratories with solutions that improve quality, enhance laboratory system productivity, and provide accurate detection of a broad range of infectious diseases and cancers. Recent advances in micro- and nanoscience and engineering, in particular in the areas of particles and microfluidic technologies, have advanced the "lab-on-a-chip" concept towards the development of a new generation of point-of-care diagnostic devices that could significantly enhance test sensitivity and speed. In this review, we will discuss many of the recent advances in microfluidics and particle technologies with an eye towards merging these two technologies for application in medical diagnostics. Although the potential diagnostic applications are virtually unlimited, the most important applications are foreseen in the areas of biomarker research, cancer diagnosis, and detection of infectious microorganisms. C1 [Konry, Tania; Bale, Shyam Sundhar; Bhushan, Abhinav; Shen, Keyue; Yarmush, Martin] Harvard Univ, Sch Med, Ctr Engn Med & Surg Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Konry, Tania; Bale, Shyam Sundhar; Bhushan, Abhinav; Shen, Keyue; Yarmush, Martin] Shriners Hosp Children, Boston, MA 02114 USA. [Seker, Erkin] Univ Calif Davis, Dept Elect & Comp Engn, Davis, CA 95616 USA. [Polyak, Boris] Drexel Univ, Dept Surg, Coll Med, Philadelphia, PA 19102 USA. RP Konry, T (reprint author), Harvard Univ, Sch Med, Ctr Engn Med & Surg Serv, Massachusetts Gen Hosp, 51 Blossom St, Boston, MA 02114 USA. EM konry.tania@gmail.com; IReis@sbi.org RI 李, 涵/B-4995-2012; OI Seker, Erkin/0000-0003-2401-3562 FU NIBIB NIH HHS [P41 EB002503] NR 110 TC 12 Z9 12 U1 9 U2 71 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0026-3672 J9 MICROCHIM ACTA JI Microchim. Acta PD FEB PY 2012 VL 176 IS 3-4 BP 251 EP 269 DI 10.1007/s00604-011-0705-1 PG 19 WC Chemistry, Analytical SC Chemistry GA 887IZ UT WOS:000299921400001 PM 25378716 ER PT J AU Kelly, TJ Souza, AL Clish, CB Puigserver, P AF Kelly, Timothy J. Souza, Amanda L. Clish, Clary B. Puigserver, Pere TI A Hypoxia-Induced Positive Feedback Loop Promotes Hypoxia-Inducible Factor 1 alpha Stability through miR-210 Suppression of Glycerol-3-Phosphate Dehydrogenase 1-Like (vol 31, pg 2696, 2011) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction C1 [Kelly, Timothy J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD USA. Broad Inst MIT & Harvard, Metabolite Profiling Initiat, Cambridge, MA USA. RP Kelly, TJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2012 VL 32 IS 4 BP 898 EP 898 DI 10.1128/MCB.06639-11 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 887GC UT WOS:000299913900016 ER PT J AU Bardelli, A Janne, PA AF Bardelli, Alberto Jaenne, Pasi A. TI The road to resistance: EGFR mutation and cetuximab SO NATURE MEDICINE LA English DT Editorial Material ID COLORECTAL-CANCER; ACQUIRED-RESISTANCE; PANITUMUMAB AB Some individuals with colorectal cancer benefit from therapies targeting the epidermal growth factor receptor (EGFR). However, resistance to EGFR blockade inevitably occurs. The characterization of a new mechanism of resistance to the EGFR-specific antibody cetuximab provides clues into how therapeutic strategies might be designed to overcome this specific resistance mechanism (pages 221-223). C1 [Bardelli, Alberto] Univ Turin, Mol Genet Lab, Inst Canc Res & Treatment, Sch Med, Turin, Italy. [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Bardelli, A (reprint author), Univ Turin, Mol Genet Lab, Inst Canc Res & Treatment, Sch Med, Turin, Italy. EM pjanne@partners.org NR 14 TC 25 Z9 25 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 2012 VL 18 IS 2 BP 199 EP 200 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 890JG UT WOS:000300140300025 PM 22310681 ER PT J AU Wang, X Roberts, CWM AF Wang, Xi Roberts, Charles W. M. TI Cancer-fighting Smurf SO NATURE MEDICINE LA English DT Editorial Material ID E3 UBIQUITIN LIGASE; HISTONE H2B; LYMPHOMA; TARGETS; SYSTEM AB A newly identified role for SMAD specific E3 ubiquitin protein ligase 2 (Smurf2) in the regulation of histone ubiquitination uncovers a broad tumor suppressor activity that helps to maintain genomic stability in mice. A recent study suggests a new mechanism underlying the role of ubiquitination in cancer (pages 227-234). C1 [Wang, Xi; Roberts, Charles W. M.] Harvard Univ, Sch Med,Dept Pediat, Dana Farber Canc Inst,Childrens Hosp Boston, Dept Pediat Oncol,Div Hematol Oncol, Boston, MA 02115 USA. RP Wang, X (reprint author), Harvard Univ, Sch Med,Dept Pediat, Dana Farber Canc Inst,Childrens Hosp Boston, Dept Pediat Oncol,Div Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu NR 19 TC 1 Z9 2 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 2012 VL 18 IS 2 BP 204 EP 205 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 890JG UT WOS:000300140300028 PM 22310684 ER PT J AU Lanner, JT Georgiou, DK Dagnino-Acosta, A Ainbinder, A Cheng, Q Joshi, AD Chen, ZW Yarotskyy, V Oakes, JM Lee, CS Monroe, TO Santillan, A Dong, KK Goodyear, L Ismailov, II Rodney, GG Dirksen, RT Hamilton, SL AF Lanner, Johanna T. Georgiou, Dimitra K. Dagnino-Acosta, Adan Ainbinder, Alina Cheng, Qing Joshi, Aditya D. Chen, Zanwen Yarotskyy, Viktor Oakes, Joshua M. Lee, Chang Seok Monroe, Tanner O. Santillan, Arturo Dong, Keke Goodyear, Laurie Ismailov, Iskander I. Rodney, George G. Dirksen, Robert T. Hamilton, Susan L. TI AICAR prevents heat-induced sudden death in RyR1 mutant mice independent of AMPK activation SO NATURE MEDICINE LA English DT Article ID EXERCISE-INDUCED RHABDOMYOLYSIS; MALIGNANT HYPERTHERMIA; SKELETAL-MUSCLE; PROTEIN-KINASE; RYANODINE RECEPTOR; SARCOPLASMIC-RETICULUM; S-NITROSYLATION; CA2+ RELEASE; STROKE; IDENTIFICATION AB Mice with a knock-in mutation (Y524S) in the type I ryanodine receptor (Ryr1), a mutation analogous to the Y522S mutation that is associated with malignant hyperthermia in humans, die when exposed to short periods of temperature elevation (>= 37 degrees C). We show here that treatment with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) prevents this heat-induced sudden death in this mouse model. The protection by AICAR is independent of AMP-activated protein kinase (AMPK) activation and results from a newly identified action of the compound on mutant Ryr1 to reduce Ca2+ leak from the sarcoplasmic reticulum to the sarcoplasm. AICAR thus prevents Ca2+-dependent increases in the amount of both reactive oxygen species (ROS) and reactive nitrogen species (RNS) that act to further increase resting Ca2+ concentrations. If unchecked, the temperature-driven increases in resting Ca2+ concentrations and the amounts of ROS and RNS create an amplifying cycle that ultimately triggers sustained muscle contractions, rhabdomyolysis and death. Although antioxidants are effective in reducing this cycle in vitro, only AICAR prevents heat-induced death in vivo. Our findings suggest that AICAR is probably effective in prophylactic treatment of humans with enhanced susceptibility to exercise- and/or heat-induced sudden death associated with RYR1 mutations. C1 [Lanner, Johanna T.; Georgiou, Dimitra K.; Dagnino-Acosta, Adan; Cheng, Qing; Joshi, Aditya D.; Chen, Zanwen; Oakes, Joshua M.; Lee, Chang Seok; Monroe, Tanner O.; Santillan, Arturo; Dong, Keke; Ismailov, Iskander I.; Rodney, George G.; Hamilton, Susan L.] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. [Ainbinder, Alina; Yarotskyy, Viktor; Dirksen, Robert T.] Univ Rochester, Med Ctr, Dept Physiol & Pharmacol, Rochester, NY 14642 USA. [Goodyear, Laurie] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Hamilton, SL (reprint author), Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. EM susanh@bcm.edu OI Lanner, Johanna/0000-0002-1222-9473 FU US National Institutes of Health [AR053349]; Department of Defense [DAMD W81XWH-10-2-0117]; Muscular Dystrophy Association of America; The Swedish Research Council; The Mexican National Council of Science and Technology [150489] FX This work was supported by grants from US National Institutes of Health (AR053349), the Department of Defense (DAMD W81XWH-10-2-0117) and the Muscular Dystrophy Association of America. J.T.L. was supported by a postdoc fellowship from The Swedish Research Council. A.D.-A. was supported by a postdoctoral fellowship from The Mexican National Council of Science and Technology (150489). The model shown in Figure 6 was created by S.A. Weldon. NR 48 TC 41 Z9 41 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 2012 VL 18 IS 2 BP 244 EP 251 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 890JG UT WOS:000300140300038 PM 22231556 ER PT J AU Kohli, P Cannon, CP AF Kohli, Payal Cannon, Christopher P. TI ACUTE CORONARY SYNDROMES IN 2011Walking the tightrope between efficacy and bleeding SO NATURE REVIEWS CARDIOLOGY LA English DT Editorial Material AB Major advances in the diagnosis of acute coronary syndromes (ACS) have occurred in 2011, but physicians treating ACS still walk the tightrope between efficacy and bleeding. Key publications have shed light on this delicate balance and heralded a new era of novel oral anticoagulants for the treatment of ACS. C1 [Kohli, Payal; Cannon, Christopher P.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Kohli, Payal; Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM cpcannon@partners.org NR 8 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 1759-5002 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD FEB PY 2012 VL 9 IS 2 BP 69 EP 71 DI 10.1038/nrcardio.2011.206 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 888AG UT WOS:000299975600001 PM 22182956 ER PT J AU Kim, H Yang, KL Dejsuphong, D D'Andrea, AD AF Kim, Hyungjin Yang, Kailin Dejsuphong, Donniphat D'Andrea, Alan D. TI Regulation of Rev1 by the Fanconi anemia core complex SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID CROSS-LINK REPAIR; DNA-DAMAGE TOLERANCE; TRANSLESION SYNTHESIS; POLYMERASE SWITCH; PATHWAY; UBIQUITIN; PROTEIN; ROLES; PCNA; ETA AB The 15 known Fanconi anemia proteins cooperate in a pathway that regulates DNA interstrand cross-link repair. Recent studies indicate that the Fanconi anemia pathway also controls Rev1-mediated translesion DNA synthesis (Us). We identified Fanconi anemia associated protein (FAAP20), an integral subunit of the multisubunit Fanconi anemia core complex. FAAP20 binds to FANCA subunit and is required for stability of the complex and monoubiquitination of FANCD2. FAAP20 contains a ubiquitin-binding zinc finger 4 domain and binds to the monoubiquitinated form of Rev1. FAAP20 binding stabilizes Rev1 nuclear foci and promotes interaction of the Fanconi anemia core with PCNA Rev1 DNA damage bypass complexes. FAAP20 therefore provides a critical link between the Fanconi anemia pathway and Us polymerase activity. We propose that the Fanconi anemia core complex regulates cross-link repair by channeling lesions to damage bypass pathways and preventing large DNA insertions and deletions. C1 [Kim, Hyungjin; Yang, Kailin; Dejsuphong, Donniphat; D'Andrea, Alan D.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Yang, Kailin] Harvard Univ, Sch Med, Leder Human Biol Program, Biol & Biomed Sci Program, Boston, MA USA. RP D'Andrea, AD (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu RI Yang, Kailin/D-7966-2013; Yang, Kailin/L-2205-2013 OI Yang, Kailin/0000-0001-5968-6738 FU Leukemia and Lymphoma Society; [RO1DK43889]; [RO1HL52725] FX We thank L.A. Moreau for chromosome aberration assay and K. Hofmann (Miltenyi Biotec), I. Dikic (Institute of Biochemistry II), A.R. Lehmann (University of Sussex), and E.H.-Y. Cheng (Memorial Sloan-Kettering Cancer Center) for reagents. We also thank members of D'Andrea laboratory for valuable input and helpful discussions. H.K. is a recipient of the Leukemia and Lymphoma Society Career Development Fellowship. K.Y is a Harvard University Presidential Scholar. This work was supported by grants RO1DK43889 and RO1HL52725 to A.D.D. NR 44 TC 76 Z9 84 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD FEB PY 2012 VL 19 IS 2 BP 164 EP 170 DI 10.1038/nsmb.2222 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 888UF UT WOS:000300029400008 PM 22266823 ER PT J AU Qiu, WH Derr, ND Goodman, BS Villa, E Wu, D Shih, W Reck-Peterson, SL AF Qiu, Weihong Derr, Nathan D. Goodman, Brian S. Villa, Elizabeth Wu, David Shih, William Reck-Peterson, Samara L. TI Dynein achieves processive motion using both stochastic and coordinated stepping SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID HAND-OVER-HAND; CYTOPLASMIC DYNEIN; MYOSIN-V; MICROTUBULE-BINDING; MOTOR DOMAIN; KINESIN; DYNACTIN; LOCALIZATION; ARCHITECTURE; MECHANISMS AB Processivity, the ability of single molecules to move continuously along a track, is a fundamental requirement of cargo-transporting molecular motors. Here, we investigate how cytoplasmic dynein, a homodimeric, microtubule-based motor, achieves processive motion. To do this, we developed a versatile method for assembling Saccharomyces cerevisiae dynein heterodimers, using complementary DNA oligonucleotides covalently linked to dynein monomers labeled with different organic fluorophores. Using two-color, single-molecule microscopy and high-precision, two-dimensional tracking, we find that dynein has a highly variable stepping pattern that is distinct from all other processive cytoskeletal motors, which use 'hand-over-hand' mechanisms. Uniquely, dynein stepping is stochastic when its two motor domains are close together. However, coordination emerges as the distance between motor domains increases, implying that a tension-based mechanism governs these steps. This plasticity may allow tuning of dynein for it diverse cellular functions. C1 [Qiu, Weihong; Derr, Nathan D.; Goodman, Brian S.; Reck-Peterson, Samara L.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Derr, Nathan D.; Shih, William] Dana Farber Canc Inst, Boston, MA 02115 USA. [Derr, Nathan D.; Shih, William] Harvard Univ, Sch Med, Dept Biochem & Mol Pharmacol, Boston, MA USA. [Villa, Elizabeth] Max Planck Inst Biochem, Dept Mol Struct Biol, D-82152 Martinsried, Germany. [Villa, Elizabeth; Wu, David] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [Wu, David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Shih, William] Harvard Univ, Wyss Inst, Boston, MA USA. RP Reck-Peterson, SL (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM reck-peterson@hms.harvard.edu RI Qiu, Weihong/F-6790-2012; Villa, Elizabeth/D-1811-2010; OI Villa, Elizabeth/0000-0003-4677-9809; Qiu, Weihong/0000-0003-1413-1389 FU American Heart Association; Rita Allen Foundation; Harvard Armenise Foundation; US National Institutes of Health [1 DP2 OD004268-01] FX We thank X. Su and D. Penman (Harvard Medical School) for providing purified kinesin-8; S. Zou for technical assistance; A. Carter, S. Churchman, A. Gennerich, Y Goldman, A. Hendricks,). Huang, A. Leschziner and A. Roberts for critical comments on the manuscript; F. Aguet, A. Besser, M. Vilela and G. Danuser for discussions of data analysis; M. Bagonis for early work on oligomer-SNAP linking; A. Leschziner for help with figure design; and A. Carter for providing MATLAB code. W.Q. is supported by a postdoctoral fellowship from the American Heart Association. S.L.R.-P. is funded by the Rita Allen Foundation, the Harvard Armenise Foundation and a US National Institutes of Health New Innovator award (1 DP2 OD004268-01). NR 54 TC 80 Z9 80 U1 0 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD FEB PY 2012 VL 19 IS 2 BP 193 EP 200 DI 10.1038/nsmb.2205 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 888UF UT WOS:000300029400012 PM 22231401 ER PT J AU Koepsell, TD Littman, AJ Forsberg, CW AF Koepsell, Thomas D. Littman, Alyson J. Forsberg, Christopher W. TI Obesity, Overweight, and Their Life Course Trajectories in Veterans and Non-Veterans SO OBESITY LA English DT Article ID BODY-MASS INDEX; WAIST CIRCUMFERENCE; PHYSICAL-ACTIVITY; RISK-FACTORS; WEIGHT; HEIGHT; RATIO; RECRUITS; SAMPLE; FAT AB Veterans comprise a large and growing segment of the US population. Results from national telephone surveys suggest higher prevalence of overweight among Veterans compared with demographically similar non-Veterans, based on self-reported height and weight. Using 1999-2008 data from the National Health and Nutrition Examination Survey (NHANES), we compared 3,768 Veterans and 21,974 non-Veterans on: (i) several measures of adiposity based on direct anthropometry; (ii) life-course of self-reported BMI; and (iii) behaviors related to weight loss or maintenance. Whether Veterans were more likely than demographically similar non-Veterans to be obese or overweight depended on the adiposity measure employed. On BMI, Veterans were about equally likely to be obese (30+ kg/m(2)), but more likely to be overweight (25-29.9 kg/m(2)) by both self-report and by direct measurement (significantly so only by self-report). On waist-stature ratio, a roughly similar pattern was observed. On waist circumference, Veterans tended to have larger values than demographically similar non-Veterans, with more Veterans in the largest two categories. But on dual-photon X-ray absorptiometry, Veterans were less likely to have 35+% body fat than non-Veterans of similar age, gender, and race/ethnicity. Life-course trends in self-reported BMI suggested a possible burst of weight gain after military discharge. These results suggest that Veterans may, on average, have less excess body fat than non-Veterans-a pattern not revealed by standard anthropometric measures. C1 [Koepsell, Thomas D.; Littman, Alyson J.; Forsberg, Christopher W.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. [Koepsell, Thomas D.; Littman, Alyson J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Koepsell, Thomas D.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Koepsell, TD (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. EM koepsell@u.washington.edu FU Office of Research and Development; Department of Veterans Affairs; VA Puget Sound Health Care System; Cooperative Studies Program FX This manuscript is based upon work supported by the Office of Research and Development, Cooperative Studies Program, Department of Veterans Affairs and the VA Puget Sound Health Care System. The contents do not necessarily represent the views of the Department of Veterans Affairs or the US Government. NR 20 TC 24 Z9 24 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD FEB PY 2012 VL 20 IS 2 BP 434 EP 439 DI 10.1038/oby.2011.2 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 883AD UT WOS:000299604100026 PM 21293452 ER PT J AU Sohn, MW Budiman-Mak, E Oh, EH Park, MS Stuck, RM Stone, NJ Pearce, WB AF Sohn, Min-Woong Budiman-Mak, Elly Oh, Elissa H. Park, Michael S. Stuck, Rodney M. Stone, Neil J. Pearce, William B. TI Obesity Paradox in Amputation Risk Among Nonelderly Diabetic Men SO OBESITY LA English DT Article ID VASCULAR COMPLICATIONS; OVERWEIGHT AB The association between BMI and amputation risk is not currently well known. We used data for a cohort of diabetic patients treated in the US Department of Veterans Affairs Healthcare System in 2003. Men aged <65 years at the end of follow-up were examined for their amputation risk and amputation-free survival during the next 5 years (2004-2008). Compared to overweight individuals (BMI 25-29.9 kg/m(2)), the risks of amputation and treatment failure (amputation or death) were higher for patients with BMI <25 kg/m(2) and were lower for those with BMI >= 30kg/m(2). Individuals with BMI kg/m(2) were only half as likely to experience any (hazard ratios (HR) = 0.49; 95% confidence interval (Cl), 0.30-0.80) and major amputations (HR = 0.53; 95% CI, 0.39-0.73) during follow-up as overweight individuals. While the amputation risk continued to decrease for higher BMI, amputation-free survival showed a slight upturn at BMI >40 kg/m(2). The association between obesity and amputation risk in our data shows a pattern consistent with "obesity paradox" observed in many health conditions. More research is needed to better understand pathophysiological mechanisms that may explain the paradoxical association between obesity and lower-extremity amputation (LEA) risk. C1 [Sohn, Min-Woong; Budiman-Mak, Elly] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Sohn, Min-Woong; Oh, Elissa H.] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA. [Budiman-Mak, Elly] Loyola Univ, Stritch Sch Med, Dept Med, Maywood, IL 60153 USA. [Park, Michael S.; Pearce, William B.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Stuck, Rodney M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Surg Serv, Hines, IL 60141 USA. [Stuck, Rodney M.] Loyola Univ, Stritch Sch Med, Dept Orthoped Surg, Maywood, IL 60153 USA. [Stone, Neil J.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. RP Sohn, MW (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. EM Min-Woong.Sohn@va.gov RI Sohn, Min-Woong/C-3560-2015 OI Sohn, Min-Woong/0000-0002-9474-2907 FU Center for Management of Complex Chronic Care, Hines VA Hospital, Hines, IL [LIP 42-099] FX The authors gratefully acknowledge the financial support from the Center for Management of Complex Chronic Care, Hines VA Hospital, Hines, IL (LIP 42-099; E.B-M., MD, Principal Investigator). The paper presents the findings and conclusions of the authors; it does not necessarily represent the Department of Veterans Affairs or Health Services Research and Development Service. The corresponding author had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 13 TC 7 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD FEB PY 2012 VL 20 IS 2 BP 460 EP 462 DI 10.1038/oby.2011.301 PG 3 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 883AD UT WOS:000299604100031 PM 21996669 ER PT J AU New, AS AF New, Antonia S. TI Commentary on Schizoid personality disorder-the peculiarities of their interpersonal relationships and existential roles' by Nirestean, et al. SO PERSONALITY AND MENTAL HEALTH LA English DT Editorial Material C1 [New, Antonia S.] Mt Sinai Sch Med, New York, NY 10029 USA. [New, Antonia S.] James J Peters VAMC, Mental Illness Res Educ & Clin Care Ctr, Bronx, NY USA. RP New, AS (reprint author), Mt Sinai Sch Med, New York, NY 10029 USA. EM Antonia.new@mssm.edu NR 2 TC 0 Z9 0 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1932-8621 J9 PERSONAL MENT HEALTH JI Personal. Ment. Health PD FEB PY 2012 VL 6 IS 1 BP 83 EP 85 DI 10.1002/pmh.1180 PG 3 WC Psychiatry; Psychology, Social SC Psychiatry; Psychology GA 887RM UT WOS:000299946800010 ER PT J AU Reitmair, A Sachs, G Bin Im, W Wheeler, L AF Reitmair, Armin Sachs, George Bin Im, Wha Wheeler, Larry TI C6orf176: a novel possible regulator of cAMP-mediated gene expression SO PHYSIOLOGICAL GENOMICS LA English DT Article DE cAMP signaling; gene expression; intraocular pressure; prostaglandins PGE2 ID ELEMENT-BINDING PROTEIN; BETA-CELL SURVIVAL; NONCODING RNAS; HUMAN GENOME; KINASE-A; PHOSPHORYLATION; ANTISENSE; CREB; TRANSCRIPTION AB Reitmair A, Sachs G, Im WB, Wheeler L. C6orf176: a novel possible regulator of cAMP-mediated gene expression. Physiol Genomics 44: 152-161, 2012. First published November 22, 2011; doi:10.1152/physiolgenomics.00089.2011.-cAMP mediates diverse cellular signals including prostaglandin (PG) E-2-mediated intraocular pressure (IOP)-lowering activity in human ocular ciliary smooth muscle cells (hCSM). We have identified gene regulatory networks and key genes upon activation of the cAMP pathway in hCSM, using novel agonists highly selective for PGE(2) receptor subtypes EP2 or EP4, which are G protein-coupled receptors well known to activate cAMP signaling. Here we describe a novel, EP2/EP4-induced, primate-specific gene of hitherto unknown function, also known as C6orf176 (chromosome 6 open reading frame 176) and recently reclassified as noncoding RNA in NCBI's database. Its expression, as determined by quantitative real-time RT-PCR (qRT-PCR), is dramatically upregulated (>2,000-fold) subsequent to transduction of EP2/EP4/Gs/cAMP signaling not only in hCSM, but also in HEK cells overexpressing the recombinant receptors. Moreover, activation of other IOP lowering, Gs-coupled prostanoid receptors, such as DP1 and IP, as well as a direct activator of adenylyl cyclase, forskolin, also substantially upregulated C6orf176 in hCSM, while FP and TP, which are Gq-coupled prostanoid receptor subtypes, did not. Novel transcript variants carrying open reading frames, derived from an at least 67 kb genomic locus on chromosome 6q27 with putative alternative transcription start sites, were identified. Transcriptional upregulation of transcript variants as well as of two genes expressed in antisense orientation that partially overlap the transcribed C6orf176 region was observed, to varying degrees, subsequent to induction of cAMP signaling using various agonists. Small interfering RNA-mediated C6orf176 gene silencing experiments showed modulation of several cAMP-responsive genes. These transcriptional activities identify C6orf176 as a potential biomarker and/or therapeutic target in context with diseases linked to deregulated cAMP signaling. Also, the cAMP-inducible C6orf176 gene locus could be useful as a model system for studying transcriptional regulation by chromatin and RNA polymerase II. C1 [Reitmair, Armin; Bin Im, Wha; Wheeler, Larry] Allergan Pharmaceut Inc, Dept Biol Sci, Irvine, CA 92612 USA. [Sachs, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. [Sachs, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Sachs, George] W Los Angeles Vet Affairs Med Ctr, Membrane Biol Lab, Los Angeles, CA 90073 USA. RP Reitmair, A (reprint author), Allergan Pharmaceut Inc, Dept Biol Sci, RD3,2525 Dupont Dr, Irvine, CA 92612 USA. EM reitmair_armin@allergan.com NR 29 TC 7 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 FEB PY 2012 VL 44 IS 2 BP 152 EP 161 DI 10.1152/physiolgenomics.00089.2011 PG 10 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 889BO UT WOS:000300048700005 PM 22108211 ER PT J AU Ehrlich, S Yendiki, A Greve, DN Manoach, DS Ho, BC White, T Schulz, SC Goff, DC Gollub, RL Holt, DJ AF Ehrlich, S. Yendiki, A. Greve, D. N. Manoach, D. S. Ho, B. -C. White, T. Schulz, S. C. Goff, D. C. Gollub, R. L. Holt, D. J. TI Striatal function in relation to negative symptoms in schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Dorsolateral prefrontal cortex; functional MRI; negative symptoms; schizophrenia; striatum ID DORSOLATERAL PREFRONTAL CORTEX; POSITRON EMISSION TOMOGRAPHY; WORKING-MEMORY PERFORMANCE; BASAL GANGLIA; MULTICENTER FMRI; DEFICIT SYNDROME; DOPAMINE HYPOTHESIS; ANTIPSYCHOTIC-DRUGS; REWARD PREDICTION; LIMBIC SYSTEM AB Background. Previous studies have suggested that motivational aspects of executive functioning, which may be disrupted in schizophrenia patients with negative symptoms, are mediated in part by the striatum. Negative symptoms have been linked to impaired recruitment of both the striatum and the dorsolateral prefrontal cortex (DLPFC). Here we tested the hypothesis that negative symptoms are associated primarily with striatal dysfunction, using functional magnetic resonance imaging (fMRI). Method. Working-memory load-dependent activation and gray matter volumes of the striatum and DLPFC were measured using a region-of-interest (ROI) approach, in 147 schizophrenia patients and 160 healthy controls. In addition to testing for a linear relationships between striatal function and negative symptoms, we chose a second, categorical analytic strategy in which we compared three demographically and behaviorally matched subgroups: patients with a high burden of negative symptoms, patients with minimal negative symptoms, and healthy subjects. Results. There were no differences in striatal response magnitudes between schizophrenia patients and healthy controls, but right DLPFC activity was higher in patients than in controls. Negative symptoms were inversely associated with striatal, but not DLPFC, activity. In addition, patients with a high burden of negative symptoms exhibited significantly lower bilateral striatal, but not DLPFC, activation than schizophrenia patients with minimal negative symptoms. Working memory performance, antipsychotic exposure and changes in gray matter volumes did not account for these differences. Conclusions. These data provide further evidence for a robust association between negative symptoms and diminished striatal activity. Future work will determine whether low striatal activity in schizophrenia patients could serve as a reliable biomarker for negative symptoms. Received 6 January 2011; Revised 20 May 2011; Accepted 6 June 2011; First published online 7 July 2011 C1 [Ehrlich, S.; Yendiki, A.; Greve, D. N.; Manoach, D. S.; Gollub, R. L.; Holt, D. J.] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ehrlich, S.; Manoach, D. S.; Goff, D. C.; Gollub, R. L.; Holt, D. J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ehrlich, S.] Tech Univ Dresden, Dept Child & Adolescent Psychiat, Univ Hosp Carl Gustav Carus, Dresden, Germany. [Ho, B. -C.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [White, T.; Schulz, S. C.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [White, T.; Schulz, S. C.] Univ Minnesota, Ctr Magnet Resonance Res, Minneapolis, MN 55455 USA. RP Ehrlich, S (reprint author), Harvard Univ, Sch Med,Psychiat Neuroimaging Res Program, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, CNY Bldg 120,Suite 100, Charlestown, MA 02129 USA. EM stefan@nmr.mgh.harvard.edu RI Ho, Beng-Choon/D-6959-2011; OI Ho, Beng-Choon/0000-0003-3976-1555; Ehrlich, Stefan/0000-0003-2132-4445; Gollub, Randy L./0000-0002-9434-4044 FU NIH/NCRR [P41RR14075]; Department of Energy [DE-FG02-99ER62764]; MIND Research Network; Morphometry BIRN [1U24]; Function BIRN [U24RR021992-01]; NIH.NCRR [MO1 RR025758-01]; NIMH [K23 MH076054]; NARSAD; Sidney R. Baer, Jr. Foundation; NIMH; Deutsche Forschungsgemeinschaft; AstraZeneca; Eli Lilly; [RR021382A] FX This work was supported by NIH/NCRR P41RR14075, Department of Energy DE-FG02-99ER62764, MIND Research Network, Morphometry BIRN 1U24, RR021382A, Function BIRN U24RR021992-01, NIH.NCRR MO1 RR025758-01, NIMH K23 MH076054 (D.J.H.), NARSAD with the Sidney R. Baer, Jr. Foundation (D.J.H.), NIMH Clinical Scholar Training (S.C.S.) and the Deutsche Forschungsgemeinschaft (Research Fellowship to S.E.).; In the past two years, Dr Schulz has had financial relationships with AstraZeneca (Investigator initiated grant) and Eli Lilly (Consultant; Investigator initiated grant). Dr Goff has served on the advisory board of Indevus, Takeda and Schering-Plough, has served as a consultant for Lundbeck, Eli Lilly, Medication Neurology and Schering-Plough and on a DSMB for Otsuka. NR 112 TC 15 Z9 15 U1 4 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD FEB PY 2012 VL 42 IS 2 BP 267 EP 282 DI 10.1017/S003329171100119X PG 16 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 886XL UT WOS:000299887700005 PM 21733291 ER PT J AU Kim, K Li, Y Jin, G Chong, W Liu, B Lu, J Lee, K Demoya, M Velmahos, GC Alam, HB AF Kim, Kyuseok Li, Yongqing Jin, Guang Chong, Wei Liu, Baoling Lu, Jennifer Lee, Kyoungbun deMoya, Marc Velmahos, George C. Alam, Hasan B. TI Effect of valproic acid on acute lung injury in a rodent model of intestinal ischemia reperfusion SO RESUSCITATION LA English DT Article DE Valproic acid; Acute lung injury; Ischemia reperfusion; Inflammation; Oxidative damage; Intestine ID RESPIRATORY-DISTRESS-SYNDROME; MOOD STABILIZING DRUGS; HEMORRHAGIC-SHOCK; ORGAN INJURY; RAT; LITHIUM; IDENTIFICATION; RESUSCITATION; INFLAMMATION; ACETYLATION AB Objectives: Acute lung injury (ALI) can develop during the course of many clinical conditions, and is associated with significant morbidity and mortality. Valproic acid (VPA), a well-known anti-epileptic drug, has been shown to have anti-oxidant and anti-inflammatory effects in various ischemia/reperfusion (I/R) models. The purpose of this study was to investigate whether VPA could affect survival and development of ALI in a rat model of intestinal I/R. Methods: Two experiments were performed. Experiment I: Male Sprague-Dawley rats (250-300 g) were subjected to intestinal ischemia (1 h) and reperfusion (3 h). They were randomized into 2 groups (n = 7 per group) 30 min after ischemia: Vehicle (Veh) and VPA (300 mg/kg, IV). Primary end-point for this study was survival over 4 h from the start of ischemia. Experiment II: The histological and biochemical effects of VPA treatment on lungs were examined 3 h (1 h ischemia + 2 h reperfusion) after intestinal I/R injury (Veh vs. VPA, n = 9 per group). An objective histological score was used to grade the degree of ALI. Enzyme linked immunosorbent assay (ELISA) was performed to measure serum levels of interleukins (IL-6 and 10), and lung tissue of cytokine-induced neutrophil chemoattractant (CINC) and myeloperoxidase (MPO). In addition, the activity of 8-isoprostane was analyzed for pulmonary oxidative damage. Results: In Experiment I, 4-h survival rate was significantly higher in VPA treated animals compared to Veh animals (71.4% vs. 14.3%, p = 0.006). In Experiment II, ALI was apparent in all of the Veh group animals. Treatment with VPA prevented the development of ALI, with a reduction in the histological score (3.4 +/- 0.3 vs. 5.3 +/- 0.6, p = 0.025). Moreover, compared to the Veh control group the animals from the VPA group displayed decreased serum levels of IL-6 (952 +/- 213 pg/ml vs. 7709 +/- 1990 pg/ml, p = 0.011), and lung tissue concentrations of CINC (1188 +/- 28 pg/ml vs. 1298 +/- 27 pg/ml, p < 0.05), MPO activity (368 +/- 23 ng/ml vs. 490 +/- 29 ng/ml, p < 0.05) and 8-isoprostane levels (1495 +/- 221 pg/ml vs. 2191 +/- 177 pg/ml, p < 0.05). Conclusion: VPA treatment improves survival and attenuates ALI in a rat model of intestinal I/R injury, at least in part, through its anti-oxidant and anti-inflammatory effects. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Kim, Kyuseok; Li, Yongqing; Jin, Guang; Chong, Wei; Liu, Baoling; Lu, Jennifer; deMoya, Marc; Velmahos, George C.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg,Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Kim, Kyuseok] Seoul Natl Univ, Bungdang Hosp, Dept Emergency Med, Seoul, South Korea. [Lee, Kyoungbun] Seoul Natl Univ, Dept Pathol, Seoul, South Korea. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg,Sch Med, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org OI Kim, Kyuseok/0000-0002-7991-9428 FU NIH [RO1 GM084127] FX Supported by NIH RO1 GM084127 (to HBA). Data presented at the 6th Annual Academic Surgical Congress, Huntington Beach, CA (February, 2011). NR 33 TC 24 Z9 26 U1 2 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD FEB PY 2012 VL 83 IS 2 BP 243 EP 248 DI 10.1016/j.resuscitation.2011.07.029 PG 6 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA 887NF UT WOS:000299933900027 PM 21824465 ER PT J AU Siegel, JM AF Siegel, Jerome M. TI REM sleep must have an adaptive value REPLY SO SLEEP MEDICINE REVIEWS LA English DT Letter C1 [Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Siegel, Jerome M.] Vet Adm Greater Los Angeles Healthcare Syst, Neurobiol Res 151A3, North Hills, CA 91343 USA. [Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. EM jsiegel@ucla.edu NR 3 TC 0 Z9 0 U1 2 U2 7 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1087-0792 J9 SLEEP MED REV JI Sleep Med. Rev. PD FEB PY 2012 VL 16 IS 1 BP 111 EP 111 DI 10.1016/j.smrv.2011.11.003 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 886JO UT WOS:000299850900011 ER PT J AU Furie, KL AF Furie, Karen L. TI Introduction for Advances in Stroke 2011 SO STROKE LA English DT Editorial Material DE epidemiology; health policy; imaging; risk factors; stroke care; stroke delivery C1 Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler MGH Stroke Res Ctr, Stroke Serv, Boston, MA 02114 USA. RP Furie, KL (reprint author), Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler MGH Stroke Res Ctr, Stroke Serv, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM kfurie@partners.org FU NINDS NIH HHS [P50NS051343] NR 0 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2012 VL 43 IS 2 BP 297 EP 297 DI 10.1161/STROKEAHA.111.647735 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 885RK UT WOS:000299798300003 PM 22267826 ER PT J AU Thrift, AG Vickrey, BG AF Thrift, Amanda G. Vickrey, Barbara G. TI Advances in Health Policy and Outcome 2010-2011 SO STROKE LA English DT Editorial Material DE health care; health policy; outcomes ID ISCHEMIC-STROKE; COST-EFFECTIVENESS; PREVENTION; BURDEN C1 [Thrift, Amanda G.] Monash Univ, Epidemiol & Prevent Unit, Stroke & Ageing Res Ctr STARC, Dept Med,Monash Med Ctr,So Clin Sch, Melbourne, Vic 3004, Australia. [Thrift, Amanda G.] Natl Stroke Res Inst, Heidelberg, Vic, Australia. [Vickrey, Barbara G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Vickrey, Barbara G.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Thrift, AG (reprint author), Monash Univ, Epidemiol & Prevent Unit, Stroke & Ageing Res Ctr STARC, Dept Med,Monash Med Ctr,So Clin Sch, Level 1-43-51 Kanooka Grove, Clayton, Vic 3168, Australia. EM amanda.thrift@monash.edu RI Thrift, Amanda/I-6251-2012 OI Thrift, Amanda/0000-0001-8533-4170 NR 21 TC 1 Z9 1 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2012 VL 43 IS 2 BP 300 EP 301 DI 10.1161/STROKEAHA.111.642637 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 885RK UT WOS:000299798300005 PM 22267821 ER PT J AU Bernard, TJ Manco-Johnson, MJ Lo, W MacKay, MT Ganesan, V deVeber, G Goldenberg, NA Armstrong-Wells, J Dowling, MM Roach, ES Tripputi, M Fullerton, HJ Furie, KL Benseler, SM Jordan, LC Kirton, A Ichord, R AF Bernard, Timothy J. Manco-Johnson, Marilyn J. Lo, Warren MacKay, Mark T. Ganesan, Vijeya deVeber, Gabrielle Goldenberg, Neil A. Armstrong-Wells, Jennifer Dowling, Michael M. Roach, E. Steve Tripputi, Mark Fullerton, Heather J. Furie, Karen L. Benseler, Susanne M. Jordan, Lori C. Kirton, Adam Ichord, Rebecca TI Towards a Consensus-Based Classification of Childhood Arterial Ischemic Stroke SO STROKE LA English DT Article DE pediatric; classification ID CENTRAL-NERVOUS-SYSTEM; INTERNATIONAL PEDIATRIC STROKE; CEREBRAL ARTERIOPATHIES; RISK-FACTORS; CHILDREN; SUBTYPES; VASCULITIS; CRITERIA; EPIDEMIOLOGY; ADULTS AB Background and Purpose-The implementation of uniform nomenclature and classification in adult arterial ischemic stroke (AIS) has been critical for defining outcomes and recurrence risks according to etiology and in developing risk-stratified treatments. In contrast, current classification and nomenclature in childhood AIS are often overlapping or contradictory. Our purpose was to develop a comprehensive consensus-based classification system for childhood AIS. Methods-Using a modified-Delphi method, members of the International Pediatric Stroke Study (IPSS) developed the Childhood AIS Standardized Classification And Diagnostic Evaluation (CASCADE) criteria. Two groups of pediatric stroke specialists from the IPSS classified 7 test cases using 2 methods each: (1) classification typical of the individual clinician's current clinical practice; and (2) classification based on the CASCADE criteria. Group 1 underwent in-person training in the utilization of the CASCADE criteria. Group 2 classified the same cases via an online survey, including definitions but without training. Inter-rater reliability (IRR) was assessed via multi-rater unweighted kappa-statistic. Results-In Group 1 (with training), IRR was improved using CASCADE criteria (kappa=0.78, 95% CI=[0.49, 0.94]), compared with typical clinical practice (kappa=0.40, 95% CI= [0.11, 0.60]). In Group 2 (without training), IRR was lower than among trained raters (kappa=0.61, 95% CI= [0.29, 0.77]), but higher than current practice (kappa=0.23, 95% CI= [0.03, 0.36]). Conclusions-A new, consensus-based classification system for childhood AIS, the CASCADE criteria, can be used to classify cases with good IRR. These preliminary findings suggest that the CASCADE criteria may be particularity useful in the setting of prospective multicenter studies in childhood-onset AIS, where standardized training of investigators is feasible. (Stroke. 2012;43:371-377.) C1 [Bernard, Timothy J.; Armstrong-Wells, Jennifer] Univ Colorado, Sect Child Neurol, Aurora, CO USA. [Manco-Johnson, Marilyn J.; Goldenberg, Neil A.] Univ Colorado, Sect Hematol Oncol BMT, Aurora, CO USA. Univ Colorado, Sect Hemophilia, Aurora, CO USA. [Bernard, Timothy J.; Manco-Johnson, Marilyn J.; Goldenberg, Neil A.; Armstrong-Wells, Jennifer] Univ Colorado, Thrombosis Ctr, Dept Pediat, Aurora, CO USA. [Tripputi, Mark] Univ Colorado, Dept Biostat & Informat, Sch Publ Hlth, Aurora, CO USA. [Lo, Warren; Roach, E. Steve] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Lo, Warren; Roach, E. Steve] Ohio State Univ, Sect Child Neurol, Columbus, OH 43210 USA. [MacKay, Mark T.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Childrens Neurosci Ctr, Melbourne, Vic, Australia. [Ganesan, Vijeya] UCL, Neurosci Unit, Inst Child Hlth, London, England. [deVeber, Gabrielle] Univ Toronto, Div Neurol, Toronto, ON M5S 1A1, Canada. [Benseler, Susanne M.] Univ Toronto, Div Rheumatol, Hosp Sick Children, Toronto, ON M5S 1A1, Canada. [Dowling, Michael M.] Univ Texas SW Med Ctr Dallas, Div Pediat Neurol, Dallas, TX 75390 USA. Univ Texas SW Med Ctr Dallas, Dept Pediat & Neurol, Dallas, TX 75390 USA. [Fullerton, Heather J.] Univ Calif San Francisco, Div Neurol, San Francisco, CA 94143 USA. [Furie, Karen L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Jordan, Lori C.] Johns Hopkins Univ, Sch Med, Dept Neurol, Div Pediat Neurol, Baltimore, MD 21205 USA. [Kirton, Adam] Univ Calgary, Calgary Pediat Stroke Program, Div Neurol, Alberta Childrens Hosp, Calgary, AB T2N 1N4, Canada. [Ichord, Rebecca] Univ Penn, Sch Med, Dept Neurol, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Bernard, TJ (reprint author), Childrens Hosp Colorado, B155,13123 E 16th Ave, Aurora, CO 80045 USA. EM timothy.bernard@ucdenver.edu RI Roach, Ewell/E-3958-2011; Lo, Warren/E-3531-2011; Kirton, Adam/L-8875-2016 FU National Institutes of Health, National Heart, Lung, and Blood Institute [1K23HL096895-01A1, 1K23HL084055-01A1]; Centers for Disease Control and Prevention [UR6/CCU820552]; National Institutes of Health, North and Central Texas Clinical and Translational Science Initiative [KL2RR024983]; First American Real Estate Information Services, Inc.; National Institutes of Health, National Institute of Neurological Disease and Stroke [R01NS050488] FX T.J.B. was supported by a grant from the National Institutes of Health, National Heart, Lung, and Blood Institute (1K23HL096895-01A1). M.J.M.-J. was supported by the Centers for Disease Control and Prevention (UR6/CCU820552). N.A.G. was supported by the National Institutes of Health, National Heart Lung and Blood Institute (1K23HL084055-01A1;). M.M.D. was supported by the National Institutes of Health, North and Central Texas Clinical and Translational Science Initiative (KL2RR024983) and First American Real Estate Information Services, Inc. R.I. was supported by the National Institutes of Health, National Institute of Neurological Disease and Stroke (R01NS050488). NR 30 TC 38 Z9 41 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2012 VL 43 IS 2 BP 371 EP 377 DI 10.1161/STROKEAHA.111.624585 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 885RK UT WOS:000299798300019 PM 22156694 ER PT J AU Rost, NS Biffi, A Cloonan, L Chorba, J Kelly, P Greer, D Ellinor, P Furie, KL AF Rost, Natalia S. Biffi, Alessandro Cloonan, Lisa Chorba, John Kelly, Peter Greer, David Ellinor, Patrick Furie, Karen L. TI Brain Natriuretic Peptide Predicts Functional Outcome in Ischemic Stroke SO STROKE LA English DT Article DE acute stroke; biomarkers; brain infarction; heart brain; outcomes ID C-REACTIVE PROTEIN; ATRIAL-FIBRILLATION; HEART-FAILURE; EXTERNAL VALIDATION; RECOVERY; MORTALITY; DEATH; HOSPITALIZATION; CLASSIFICATION; BIOMARKERS AB Background and Purpose-Elevated serum levels of brain natriuretic peptide (BNP) have been associated with cardioembolic stroke and increased poststroke mortality. We sought to determine whether BNP levels were associated with functional outcome after ischemic stroke. Methods-We measured BNP in consecutive patients aged years admitted to our stroke unit between 2002 to 2005. BNP quintiles were used for analysis. Stroke subtypes were assigned using Trial of ORG 10172 in Acute Stroke Treatment criteria. Outcomes were measured as 6-month modified Rankin Scale score ("good outcome"=0-2 versus "poor") as well as mortality. Multivariate logistic regression was used to assess association between the quintiles of BNP and outcomes. Predictive performance of BNP as compared with clinical model alone was assessed by comparing receiver operating characteristic curves. Results-Of 569 patients with ischemic stroke, 46% were female; mean age was 67.9 +/- 15 years. In age- and gender-adjusted analysis, elevated BNP was associated with lower ejection fraction (P<0.0001) and left atrial dilatation (P<0.001). In multivariate analysis, elevated BNP decreased the odds of good functional outcome (OR, 0.64; 95% CI, 0.41-0.98) and increased the odds of death (OR, 1.75; 95% CI, 1.36-2.24) in these patients. Addition of BNP to multivariate models increased their predictive performance for functional outcome (P=0.013) and mortality (P<0.03) after cardioembolic stroke. Conclusions-Serum BNP levels are strongly associated with cardioembolic stroke and functional outcome at 6 months after ischemic stroke. Inclusion of BNP improved prediction of mortality in patients with cardioembolic stroke. (Stroke. 2012;43:441-445.) C1 [Rost, Natalia S.; Biffi, Alessandro; Cloonan, Lisa; Furie, Karen L.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA 02114 USA. [Ellinor, Patrick] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kelly, Peter] Mater Univ Hosp, Stroke Serv, Dublin, Ireland. [Greer, David] Yale Univ, Med Ctr, Dept Neurol, New Haven, CT USA. [Chorba, John] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. RP Rost, NS (reprint author), Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org FU National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) [K23NS064052, 5P50NS051343-04]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010N]; Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; [1R01HL092577]; [1R01HL104156]; [5R21DA027021]; [1K24HL105780] FX Supported by the National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) K23NS064052 (N.S.R.); NIH-NINDS 5P50NS051343-04 (K.L.F.); and 1R01HL092577, 1R01HL104156, 5R21DA027021, 1K24HL105780 (P.T.E.); the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010N), and the Deane Institute for Integrative Study of Atrial Fibrillation and Stroke. NR 43 TC 36 Z9 39 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2012 VL 43 IS 2 BP 441 EP 445 DI 10.1161/STROKEAHA.111.629212 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 885RK UT WOS:000299798300029 PM 22116811 ER PT J AU Zhu, XX Tao, LY Tejima-Mandeville, E Qiu, JH Park, J Garber, K Ericsson, M Lo, EH Whalen, MJ AF Zhu, Xiaoxia Tao, Luyang Tejima-Mandeville, Emiri Qiu, Jianhua Park, Juyeon Garber, Kent Ericsson, Maria Lo, Eng H. Whalen, Michael J. TI Plasmalemma Permeability and Necrotic Cell Death Phenotypes After Intracerebral Hemorrhage in Mice SO STROKE LA English DT Article DE apoptosis; inflammation; intracerebral hemorrhage; mice; necrosis; plasmalemma ID CONTROLLED CORTICAL IMPACT; CEREBRAL-ISCHEMIA; HYPOXIA-ISCHEMIA; NEONATAL-RAT; BRAIN-INJURY; APOPTOSIS; NECROSIS; MOUSE; INHIBITION; ASTROCYTES AB Background and Purpose-Traumatic and ischemic brain injury induce plasmalemma permeability and necrosis; however, no studies have examined these aspects of cellular injury in intracerebral hemorrhage models. Methods-In vivo propidium iodide (PI) and YOYO-1 were used to assess plasmalemma damage after collagenase-induced intracerebral hemorrhage in mice. Ex vivo aspartylglutamylvalylaspartic acid, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, and electron microscopy were used to assess the relationship between plasmalemma permeability and mode of cell death. Cell types vulnerable to plasmalemma damage were determined by immunohistochemistry. Results-Plasma lemma permeability was first detected in the lesion at 1 to 3 hours and peaked at 48 to 72 hours. Neurons and IBA-1-positive cells with morphological features of monocytes were sensitive, whereas resident microglia and astocytes were resistant to plasmalemma permeability. PI+ cells colocalized with fluorescent-labeled caspase substrates and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling beginning at 3 to 6 hours. At 48 hours, greater than half of injured cells were PI+/aspartylglutamylvalylaspartic acid- or PI+/terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling -suggesting necrosis, and <5% were PI-/terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling+ or PI-/aspartylglutamylvalylaspartic acid+. Electron microscopy confirmed ultrastructural features of necrosis at 24 hours after intracerebral hemorrhage, high mobility group box protein-1 was released from permeable cells, and mice deficient in receptor interacting protein kinase (RIPK) 3, a known necrosis trigger, had 50% less PI+ cells at 24 hours. Permeable cells remained in the brain for at least 24 hours with <10% spontaneous resealing. Conclusions-Necrosis contributes to cell demise after intracerebral hemorrhage. Programmed necrosis and plasmalemma damage may represent novel therapeutic targets to prevent cell death or rescue injured cells after intracerebral hemorrhage. (Stroke. 2012;43:524-531.) C1 [Whalen, Michael J.] Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Ctr Neurosci, Charlestown, MA 02129 USA. [Zhu, Xiaoxia; Tao, Luyang; Qiu, Jianhua; Park, Juyeon; Garber, Kent; Whalen, Michael J.] Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. [Tejima-Mandeville, Emiri; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Tejima-Mandeville, Emiri; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Zhu, Xiaoxia] Fudan Univ, Huashan Hosp, Dept Rheumatol, Shanghai 200433, Peoples R China. [Tao, Luyang] Soochow Univ, Dept Forens Med, Suzhou, Peoples R China. [Ericsson, Maria] Harvard Univ, Sch Med, Electron Microscopy Facil, Boston, MA USA. RP Whalen, MJ (reprint author), Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Ctr Neurosci, 149 13th St, Charlestown, MA 02129 USA. EM MWhalen@Partners.org FU China Natural Science Foundation [30571909, 30872666, R37-NS37074, P01-NS55104, RO1NS061255, RO1NS064545] FX Supported by the China Natural Science Foundation (30571909 and 30872666, L.T.), R37-NS37074, P01-NS55104 (E.H.L.), and RO1NS061255, RO1NS064545 (M.J.W.). NR 36 TC 22 Z9 23 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2012 VL 43 IS 2 BP 524 EP 531 DI 10.1161/STROKEAHA.111.635672 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 885RK UT WOS:000299798300041 PM 22076006 ER PT J AU Nogueira, RG Ferreira, R Grant, PE Maier, SE Koroshetz, WJ Gonzalez, RG Sheth, KN AF Nogueira, Raul G. Ferreira, Rafael Grant, P. Ellen Maier, Stephan E. Koroshetz, Walter J. Gonzalez, Ramon G. Sheth, Kevin N. TI Restricted Diffusion in Spinal Cord Infarction Demonstrated by Magnetic Resonance Line Scan Diffusion Imaging SO STROKE LA English DT Article DE spinal cord infarct; MRI; diffusion ID MRI; ISCHEMIA; DWI AB Background and Purpose-We report on the use of line scan diffusion magnetic resonance imaging in the evaluation of spinal cord infarctions. Methods-Data on 19 patients with clinical findings consistent with spinal cord infarctions and abnormal findings on line scan diffusion imaging were reviewed. The Apparent Diffusion Coefficient (ADC) measurements for the normal spinal cord and for the areas of abnormality were calculated from trace ADC maps. Results-Restricted diffusion was found in all 19 patients. Absolute ADC values in the ischemic area ranged between 395.4 and 575.8X10(-6) mm(2)/s, with ADC ratios ranging between 39.4% and 57.4%. Conclusions-Line scan diffusion imaging is technically feasible and appears to be a reliable method to diagnose spinal cord infarction in the acute setting. (Stroke. 2012;43:532-535.) C1 [Nogueira, Raul G.; Ferreira, Rafael; Grant, P. Ellen; Gonzalez, Ramon G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuroradiol, Boston, MA USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Dept Neurol, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA 30322 USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Dept Neurosurg, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Dept Radiol, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA 30322 USA. [Maier, Stephan E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Koroshetz, Walter J.] NIH, Washington, DC USA. [Sheth, Kevin N.] Univ Maryland, Sch Med, Shock Trauma & Anesthesiol Res Ctr, Dept Neurol Emergency Med & Neurosurg, Baltimore, MD 21201 USA. [Grant, P. Ellen] Childrens Hosp, Dept Med, Ctr Fetal Neonatal Neuroimaging & Dev Sci, Boston, MA 02115 USA. [Grant, P. Ellen] Childrens Hosp, Dept Radiol, Ctr Fetal Neonatal Neuroimaging & Dev Sci, Boston, MA 02115 USA. RP Nogueira, RG (reprint author), Emory Fac Off Bldg,80 Jesse Hill Dr SE,Room 398, Atlanta, GA 30303 USA. EM rnoguei@emory.edu FU American Heart Association; National Institutes of Health; [NIH R01 EB006867] FX R.G.N., Consultant/Scientific Advisory Board Concentric Medical, ev3 Neurovascular, CoAxia, and Rapid Medical; S.E.M., Research Grant-NIH R01 EB006867; R.G.G., Research Grant from the National Institutes of Health; K.N.S., Research Grant from the American Heart Association. NR 14 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2012 VL 43 IS 2 BP 532 EP 535 DI 10.1161/STROKEAHA.111.624023 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 885RK UT WOS:000299798300042 PM 22033988 ER PT J AU Fan, X Qiu, JH Yu, ZY Dai, HB Singhal, AB Lo, EH Wang, XY AF Fan, Xiang Qiu, Jianhua Yu, Zhanyang Dai, Haibin Singhal, Aneesh B. Lo, Eng H. Wang, Xiaoying TI A Rat Model of Studying Tissue-Type Plasminogen Activator Thrombolysis in Ischemic Stroke With Diabetes SO STROKE LA English DT Article DE diabetes; rats; thrombolytics; tPA ID EMBOLIC STROKE; HYPERGLYCEMIA; INHIBITOR; OCCLUSION; PREDICTS; THERAPY AB Background and Purpose-Poststroke hyperglycemia and diabetes mellitus are associated with lower thrombolytic efficacy and an increased risk of postischemic cerebral hemorrhage. We aimed to develop a rodent model of thrombolysis in diabetic stroke that mimics the clinical situation. Method-Male 6-week Type I diabetic rats (14 weeks old) were subjected to embolic focal stroke and treated with tissue-type plasminogen activator at 1.5 hours. Reperfusion and 24-hour neurological outcomes were measured and compared with nondiabetic control rats. Results-Diabetic rats exhibited resistance to thrombolytic reperfusion, larger infarction volumes, and increased intracerebral hemorrhage. Conclusions-This animal model would be relevant to future studies investigating pathophysiological mechanisms and in developing new therapeutic approaches to enhance the efficacy of tissue-type plasminogen activator thrombolysis in stroke patients with diabetes or poststroke hyperglycemia. (Stroke. 2012;43:567-570.) C1 [Fan, Xiang; Qiu, Jianhua; Yu, Zhanyang; Dai, Haibin; Singhal, Aneesh B.; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Sch Med, Neurosci Program,Neuroprotect Res Lab, Massachusetts Gen Hosp,Dept Neurol & Radiol, Boston, MA 02115 USA. RP Wang, XY (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. EM wangxi@helix.mgh.harvard.edu FU National Institute of Health [R01-NS065998, UO1-NS072324] FX Supported by National Institute of Health grants R01-NS065998 and UO1-NS072324 (to X.W.). NR 16 TC 23 Z9 25 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2012 VL 43 IS 2 BP 567 EP 570 DI 10.1161/STROKEAHA.111.635250 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 885RK UT WOS:000299798300052 PM 22052516 ER PT J AU De Meyer, SF Stoll, G Wagner, DD Kleinschnitz, C AF De Meyer, Simon F. Stoll, Guido Wagner, Denisa D. Kleinschnitz, Christoph TI von Willebrand Factor An Emerging Target in Stroke Therapy SO STROKE LA English DT Review DE glycoprotein Ib; platelets; stroke; von Willebrand factor ID THROMBOTIC THROMBOCYTOPENIC PURPURA; ACUTE ISCHEMIC-STROKE; NONVALVULAR ATRIAL-FIBRILLATION; CORONARY-ARTERY THROMBOSIS; PLATELET GLYCOPROTEIN IB; VWF MONOCLONAL-ANTIBODY; DRUG CANDIDATE ALX-0081; FACTOR APTAMER ARC1779; FACTOR LEVELS INCREASE; CARDIOVASCULAR-DISEASE AB Thrombus formation is of paramount importance in the pathophysiology of acute ischemic stroke. Current antithrombotics used to treat or prevent cerebral ischemia are only moderately effective or bear an increased risk of severe bleeding. von Willebrand factor (VWF) has long been known to be a key player in thrombus formation at sites of vascular damage. While the association between VWF and coronary heart disease has been well studied, knowledge about the role of VWF in stroke is much more limited. However, in recent years, an increasing amount of clinical and preclinical evidence has revealed the critical involvement of VWF in stroke development. This review summarizes the latest insights into the pathophysiologic role of VWF-related processes in ischemic brain injury under experimental conditions and in humans. Potential clinical merits of novel inhibitors of VWF-mediated platelet adhesion and activation as powerful and safe tools to combat thromboembolic disorders including ischemic stroke are discussed. Preclinical and clinical evidence illustrates an important role of VWF in ischemic stroke, suggesting that VWF could become a promising target in stroke therapy. (Stroke. 2012;43:599-606.) C1 [De Meyer, Simon F.] KULeuven Campus Kortrijk, Lab Thrombosis Res, B-8500 Kortrijk, Belgium. [De Meyer, Simon F.; Wagner, Denisa D.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [De Meyer, Simon F.; Wagner, Denisa D.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [De Meyer, Simon F.; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Stoll, Guido; Kleinschnitz, Christoph] Univ Wurzburg, Dept Neurol, D-8700 Wurzburg, Germany. RP De Meyer, SF (reprint author), KULeuven Campus Kortrijk, Lab Thrombosis Res, E Sabbelaan 53, B-8500 Kortrijk, Belgium. EM simon.demeyer@kuleuven-kortrijk.be FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL041002]; Deutsche Forschungsgemeinschaft, Bonn, Germany [SFB 688] FX This work was supported by National Heart, Lung, and Blood Institute of the National Institutes of Health grant R01 HL041002 (to D.D.W.). S.F.D.M. is a postdoctoral fellow of the Research Foundation Flanders (Fonds voor Wetenschappelijk Onderzoek Vlaanderen). G.S. and C.K. are supported by the Deutsche Forschungsgemeinschaft, Bonn, Germany, SFB 688, projects A13 and B1. NR 86 TC 49 Z9 49 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2012 VL 43 IS 2 BP 599 EP 606 DI 10.1161/STROKEAHA.111.628867 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 885RK UT WOS:000299798300058 PM 22180250 ER PT J AU Fradley, MG Thakuria, JV Collins, AB Moore, SA Stone, JR AF Fradley, Michael G. Thakuria, Joseph V. Collins, A. Bernard Moore, Stephanie A. Stone, James R. TI Direct Tissue Evaluation via Immunofluorescence in the Diagnosis of Hereditary Transthyretin Cardiac Amyloidosis SO TEXAS HEART INSTITUTE JOURNAL LA English DT Article DE Amyloid neuropathies, familial/genetics; amyloidosis, cardiac/classification/diagnosis/physiopathology/therapy; diagnostic errors/prevention & control; diflunisal; fluorescent antibody technique; immunoenzyme techniques; polyneuropathies; transthyretin-related amyloid fibril protein, human ID CLASSIFICATION; MANAGEMENT; SPECIMENS AB Multiple precursor proteins have been shown to cause cardiac amyloidosis. The most common forms are due either to immuno globulin light chains or to transthyretin proteins (either wild-type or mutant forms). Correct subclassification of the amyloid is paramount because treatment differs in accordance with the type of amyloidosis. Indirect diagnostic methods, including serologic analysis, can lead to misdiagnosis. Definitive diagnosis often requires analysis of amyloid in the tissue. We present a case of a woman who was diagnosed with hereditary transthyretin cardiac amyloidosis by means of immuno fluorescence and genetic analysis. This case highlights the importance in the diagnostic algorithm of cardiac amyloidosis of direct evaluation of the tissue with immuno fluorescence and of genetic testing. (Tex Heart Inst J 2012;39(1):71-5) C1 [Fradley, Michael G.; Moore, Stephanie A.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med,Div Cardiol, Boston, MA 02114 USA. [Thakuria, Joseph V.] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat, Sch Med,Div Clin & Biochem Genet, Boston, MA 02114 USA. [Collins, A. Bernard; Stone, James R.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, Boston, MA 02114 USA. RP Fradley, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med,Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM mfradley@partners.org NR 17 TC 0 Z9 0 U1 0 U2 0 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 J9 TEX HEART I J JI Tex. Heart Inst. J. PD FEB PY 2012 VL 39 IS 1 BP 71 EP 75 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 890AP UT WOS:000300117800016 PM 22412233 ER PT J AU Kelly, JF Hoeppner, B Stout, RL Pagano, M AF Kelly, John F. Hoeppner, Bettina Stout, Robert L. Pagano, Maria TI Determining the relative importance of the mechanisms of behavior change within Alcoholics Anonymous: a multiple mediator analysis SO ADDICTION LA English DT Article DE Addiction; alcohol dependence; alcoholics anonymous; alcoholism; depression; self-help groups; social network; spirituality ID LARGE SOCIAL NETWORK; SELF-HELP GROUPS; MULTIVARIATE PROCESS MODEL; SUBSTANCE-ABUSE; CLINICAL-TRIAL; PROJECT MATCH; REDUCE DEMAND; UNITED-STATES; FOLLOW-UP; OUTCOMES AB Aims Evidence indicates that Alcoholics Anonymous (AA) participation reduces relapse risk but less is known about the mechanisms through which AA confers this benefit. Initial studies indicate self-efficacy, negative affect, adaptive social networks and spiritual practices are mediators of this effect, but because these have been tested in isolation, their relative importance remains elusive. This study tested multiple mediators simultaneously to help determine the most influential pathways. Design Prospective, statistically controlled, naturalistic investigation examined the extent to which these previously identified mechanisms mediated AA attendance effects on alcohol outcomes controlling for baseline outcome values, mediators, treatment, and other confounders. Setting Nine clinical sites within the United States. Participants Adults (n = 1726) suffering from alcohol use disorder (AUD) initially enrolled in a randomized study with two arms: aftercare (n = 774); and out-patient (n = 952) comparing three out-patient treatments (Project MATCH). Measurements AA attendance during treatment; mediators at 9 months; and outcomes [percentage of days abstinent (PDA) and drinks per drinking day (DDD)] at 15 months. Findings Among out-patients the effect of AA attendance on alcohol outcomes was explained primarily by adaptive social network changes and increases in social abstinence self-efficacy. Among more impaired aftercare patients, in addition to mediation through adaptive network changes and increases in social self-efficacy, AA lead to better outcomes through increasing spirituality/religiosity and by reducing negative affect. The degree to which mediators explained the relationship between AA and outcomes ranged from 43% to 67%. Conclusion While Alcoholics Anonymous facilitates recovery by mobilizing several processes simultaneously, it is changes in social factors which appear to be of primary importance. C1 [Kelly, John F.; Hoeppner, Bettina] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. [Kelly, John F.; Hoeppner, Bettina] Harvard Univ, Sch Med, Boston, MA USA. [Stout, Robert L.] Decis Sci Inst PIRE, Pawtucket, RI USA. [Pagano, Maria] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, 60 Staniford St,Suite 120, Boston, MA 02114 USA. EM jkelly11@partners.org FU National Institute of Alcohol Abuse and Alcoholism (NIAAA) [R21 AA016762]; National Institute on Drug Abuse [K01 DA027097] FX This research was supported by a grant from the National Institute of Alcohol Abuse and Alcoholism (NIAAA R21 AA016762; Mechanisms and Moderators of Behavior Change in Alcoholics Anonymous) and a grant from the National Institute on Drug Abuse (K01 DA027097). The authors would also like to thank A. Eden Evins for helpful comments on an earlier draft of this manuscript. NR 63 TC 43 Z9 44 U1 6 U2 37 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD FEB PY 2012 VL 107 IS 2 BP 289 EP 299 DI 10.1111/j.1360-0443.2011.03593.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 877DC UT WOS:000299156100014 PM 21917054 ER PT J AU Tetrault, JM Tate, JP McGinnis, KA Goulet, JL Sullivan, LE Bryant, K Justice, AC Fiellin, DA AF Tetrault, Jeanette M. Tate, Janet P. McGinnis, Kathleen A. Goulet, Joseph L. Sullivan, Lynn E. Bryant, Kendall Justice, Amy C. Fiellin, David A. CA Vet Aging Cohort Study Team TI Hepatic Safety and Antiretroviral Effectiveness in HIV-Infected Patients Receiving Naltrexone SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE HIV; Naltrexone; Alcoholism; Opioid-Related Disorders ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CONTROLLED-TRIAL; HIGH-DOSE NALTREXONE; ILLICIT DRUG-USE; ALCOHOL DEPENDENCE; MEDICATION ADHERENCE; RELEASE NALTREXONE; OPIOID DEPENDENCE; THERAPY; DRINKING AB Background: We sought to determine the impact of naltrexone on hepatic enzymes and HIV biomarkers in HIV-infected patients. Methods: We used data from the Veterans Aging Cohort Study-Virtual Cohort, an electronic database of administrative, pharmacy, and laboratory data. We restricted our sample to HIV-infected patients who received an initial oral naltrexone prescription of at least 7 days duration. We examined aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and HIV biomarker (CD4 and HIV RNA) values for the 365 days prior to, during, and for the 365 days post-naltrexone prescription. We also examined cases of liver enzyme elevation (LEE; defined as > 5 times baseline ALT or AST or > 3.5 times baseline if baseline ALT or AST was > 40 IU/l). Results: Of 114 HIV-infected individuals, 97% were men, 45% white, 57% Hepatitis C co-infected; median age was 49 years; 89% of the sample had a history of alcohol dependence and 32% had opioid dependence. Median duration of naltrexone prescription was 49 (interquartile range 30 to 83) days, representing 9,525 person-days of naltrexone use. Mean ALT and AST levels remained below the upper limit of normal. Two cases of LEE occurred. Mean CD4 count remained stable and mean HIV RNA decreased after naltrexone prescription. Conclusions: In HIV-infected patients, oral naltrexone is rarely associated with clinically significant ALT or AST changes and does not have a negative impact on biologic parameters. Therefore, HIV-infected patients with alcohol or opioid dependence can be treated with naltrexone. C1 [Tetrault, Jeanette M.; Goulet, Joseph L.; Sullivan, Lynn E.; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Tate, Janet P.; McGinnis, Kathleen A.; Goulet, Joseph L.; Justice, Amy C.; Fiellin, David A.] Vet Aging Cohort Study, West Haven, CT USA. [Tate, Janet P.; Goulet, Joseph L.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [McGinnis, Kathleen A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Bryant, Kendall] NIAAA, Rockville, MD 20852 USA. RP Tetrault, JM (reprint author), 367 Cedar St,4th Floor, New Haven, CT 06510 USA. EM jeanette.tetrault@yale.edu OI Fiellin, David/0000-0002-4006-010X; Goulet, Joseph/0000-0002-0842-804X FU National Institute on Alcohol Abuse and Alcoholism [U10 AA 13566]; VHA Public Health Strategic Health Core Group; National Institute on Alcohol and Alcohol Abuse [U01 AA 13566]; National Institute on Drug Abuse (NIDA) [R01 DA019511-03, R01 DA025991, R01 DA020576-01A1, K23 DA024050-02] FX The Veterans Aging Cohort Study is funded by the National Institute on Alcohol Abuse and Alcoholism (U10 AA 13566) and the VHA Public Health Strategic Health Core Group. The material presented in this study is based upon work supported in part by funding from the National Institute on Alcohol and Alcohol Abuse (U01 AA 13566) and the National Institute on Drug Abuse (NIDA R01 DA019511-03, R01 DA025991, R01 DA020576-01A1, K23 DA024050-02). NR 46 TC 10 Z9 10 U1 2 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 FEB PY 2012 VL 36 IS 2 BP 318 EP 324 DI 10.1111/j.1530-0277.2011.01601.x PG 7 WC Substance Abuse SC Substance Abuse GA 883DS UT WOS:000299614700018 PM 21797892 ER PT J AU Kirzhner, M Jakobiec, FA AF Kirzhner, Maria Jakobiec, Frederick A. TI Clinicopathologic and Immunohistochemical Features of Pigmented Basal Cell Carcinomas of the Eyelids SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MALIGNANT BASOMELANOCYTIC TUMOR; MELANOCYTE COLONIZATION; MELANOSOME TRANSFER; OCULAR ADNEXA; BLUE NEVUS; IN-SITU; CONJUNCTIVA; SKIN; DIFFERENTIATION; KERATINOCYTES AB PURPOSE: To describe the clinical and microscopic features of pigmented basal cell carcinomas (pBCC) of the eyelid. DESIGN: Retrospective observational case series collected at one institution. METHODS: An analysis of clinical records, photographs, and histopathologic characteristics of 257 BCCs with a review of the literature. The frequencies of clinically pigmented, and of microscopically pigmented but clinically nonpigmented, BCCs were determined. Cytochemical stains (Fontana-Masson, Prussian blue) and immunohistochemical probes (S-100, microphthalmia-associated transcription factor [MiTF], HMB-45, MART-1, CK20, synaptophysin, chromogranin, CD1a, Ki-67) were then employed and the findings correlated with the degree of clinical pigmentation. RESULTS: Histopathologically, 13 of 257 cases (5.06%) were found to have pigment; of these 13, 6 (all white patients) had clinically apparent pigmentation (2.33%), either focal or diffuse. Eight of 13 lesions developed on the lower eyelids. All stained positively for melanin but negatively for iron. MiTF highlighted numerous melanocytic nuclei in the tumor lobules, while MART-1 and HMB-45 revealed the dendritic shapes of the entrapped melanocytes. There was a subtotal blockage of melanin transfer to the surrounding basaloid cells. Intralobular S-100-positive cells included CD1a-positive Langerhans cells, while CK20 did not identify any Merkel cells. CONCLUSIONS: Only 1 of 6 lesions was uniformly clinically pigmented, whereas the other 5 were only focally brown-black. The clinical pigmentation was imparted by varying densities and distributions of melanocytes with arborizing dendrites, which were present in all BCCs. Melanophages within the stroma and basaloid cell melanization also contributed to pigmentation. No behavioral or biologic differences in pBCC were documented compared with clinically nonpigmented lesions. (Am J Ophthalmol 2012;153:242-252. (C) 2012 by Elsevier Inc. All rights reserved.) C1 [Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Room 321,243 Charles St, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 72 TC 2 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 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 2012 VL 153 IS 2 BP 242 EP 252 DI 10.1016/j.ajo.2011.07.008 PG 11 WC Ophthalmology SC Ophthalmology GA 884OQ UT WOS:000299717800009 PM 21982104 ER PT J AU Hatzenbuehler, ML O'Cleirigh, C Grasso, C Mayer, K Safren, S Bradford, J AF Hatzenbuehler, Mark L. O'Cleirigh, Conall Grasso, Chris Mayer, Kenneth Safren, Steven Bradford, Judith TI Effect of Same-Sex Marriage Laws on Health Care Use and Expenditures in Sexual Minority Men: A Quasi-Natural Experiment SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PSYCHOLOGICAL DISTRESS; BISEXUAL POPULATIONS; SOCIAL STRESS; UNITED-STATES; GAY MEN; DISCRIMINATION; ORIENTATION; ADULTS; PSYCHOPATHOLOGY; PREVALENCE AB Objectives. We sought to determine whether health care use and expenditures among gay and bisexual men were reduced following the enactment of same-sex marriage laws in Massachusetts in 2003. Methods. We used quasi-experimental, prospective data from 1211 sexual minority male patients in a community-based health center in Massachusetts. Results. In the 12 months after the legalization of same-sex marriage, sexual minority men had a statistically significant decrease in medical care visits (mean=5.00 vs mean=4.67; P=.05; Cohen's d=0.17), mental health care visits (mean=24.72 vs mean=22.20; P=.03; Cohen's d=0.35), and mental health care costs (mean=$2442.28 vs mean=$2137.38; P=.01; Cohen's d=0.41), compared with the 12 months before the law change. These effects were not modified by partnership status, indicating that the health effect of same-sex marriage laws was similar for partnered and nonpartnered men. Conclusions. Policies that confer protections to same-sex couples may be effective in reducing health care use and costs among sexual minority men. (Am J Public Health. 2012;102:285-291. doi:10.2105/AJPH.2011.300382) C1 [Hatzenbuehler, Mark L.] Columbia Univ, Mailman Sch Publ Hlth, Ctr Study Social Inequal Hlth, Robert Wood Johnson Fdn Hlth & Soc, New York, NY 10032 USA. [O'Cleirigh, Conall; Mayer, Kenneth; Safren, Steven; Bradford, Judith] Fenway Inst, Ctr Populat Res Lesbian Gay Bisexual & Transgende, Boston, MA USA. [O'Cleirigh, Conall; Safren, Steven] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mayer, Kenneth] Brown Univ, Dept Med, Providence, RI 02912 USA. RP Hatzenbuehler, ML (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Ctr Study Social Inequal Hlth, Robert Wood Johnson Fdn Hlth & Soc, 722 W 168 St, New York, NY 10032 USA. EM mlh2101@columbia.edu FU Center for Population Research in LGBT Health at the Fenway Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R21HD051178]; Robert Wood Johnson Foundation FX This work was supported by the Center for Population Research in LGBT Health at the Fenway Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (award R21HD051178).; The authors also wish to thank the Robert Wood Johnson Foundation Health and Society Scholars program for its financial support NR 43 TC 60 Z9 60 U1 6 U2 30 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2012 VL 102 IS 2 BP 285 EP 291 DI 10.2105/AJPH.2011.300382 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 884ON UT WOS:000299717500020 PM 22390442 ER PT J AU Saboisky, JP Stashuk, DW Hamilton-Wright, A Carusona, AL Campana, LM Trinder, J Eckert, DJ Jordan, AS McSharry, DG White, DP Nandedkar, S David, WS Malhotra, A AF Saboisky, Julian P. Stashuk, Daniel W. Hamilton-Wright, Andrew Carusona, Andrea L. Campana, Lisa M. Trinder, John Eckert, Danny J. Jordan, Amy S. McSharry, David G. White, David P. Nandedkar, Sanjeev David, William S. Malhotra, Atul TI Neurogenic Changes in the Upper Airway of Patients with Obstructive Sleep Apnea SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE motor unit; respiration; tongue; genioglossus; respiratory ID MOTOR UNIT POTENTIALS; AMYOTROPHIC-LATERAL-SCLEROSIS; CONCENTRIC NEEDLE EMG; SOFT PALATAL MUCOSA; MUSCLE-FIBER TYPE; MACRO-EMG; GENIOGLOSSUS MUSCLE; NEUROMUSCULAR DISORDERS; QUANTITATIVE-ANALYSIS; DIAGNOSTIC YIELD AB Rationale: Controversy persists regarding the presence and importance of hypoglossal nerve dysfunction in obstructive sleep apnea (OSA). Objectives: We assessed quantitative parameters related to motor unit potential (MUP) morphology derived from electromyographic (EMG) signals in patients with OSA versus control subjects and hypothesized that signs of neurogenic remodeling would be present in the patients with OSA. Methods: Participants underwent diagnostic sleep studies to obtain apnea-hypopnea indices. Muscle activity was detected with 50-mm concentric needle electrodes. The concentric needle was positioned at more than 10 independent sites per subject, after the local anatomy of the upper airway musculature was examined by ultrasonography. All activity was quantified with subjects awake, during supine eupneic breathing while wearing a nasal mask connected to a pneumotachograph. Genioglossus EMG signals were analyzed offline by automated software (DQEMG), which extracted motor unit potential trains (MUPTs) contributed by individual motor units from the composite EMG signals. Quantitative measurements of MUP templates, including duration, peak-to-peak amplitude, area, area-to-amplitude ratio, and size index, were compared between the untreated patients with OSA and healthy control subjects. Measurements and Main Results: A total of 1,655 MUPTs from patients with OSA (n = 17; AH I, 55 +/- 6/h) and control subjects (n = 14; AHI, 4 +/- 1/h) were extracted from the genioglossus muscle EMG signals. MUP peak-to-peak amplitudes in the patients with OSA were not different compared with the control subjects (397.5 +/- 9.0 vs. 382.5 +/- 10.0 mu V). However, the MUPs of the patients with OSA were longer in duration (11.5 +/- 0.1 vs. 10.3 +/- 0.1 ms; P < 0.001) and had a larger size index (4.09 +/- 0.02 vs. 3.92 +/- 0.02; P < 0.001) compared with control subjects. Conclusions: These results confirm and quantify the extent and existence of structural neural remodeling in OSA. C1 [Saboisky, Julian P.; Carusona, Andrea L.; Eckert, Danny J.; McSharry, David G.; Malhotra, Atul] Brigham & Womens Hosp, Sleep Disorders Program, Div Sleep Med, Boston, MA 02115 USA. [Saboisky, Julian P.; Eckert, Danny J.; McSharry, David G.; White, David P.; David, William S.; Malhotra, Atul] Harvard Univ, Sch Med, Boston, MA USA. [Stashuk, Daniel W.] Univ Waterloo, Dept Syst Design Engn, Waterloo, ON N2L 3G1, Canada. [Hamilton-Wright, Andrew] Mt Allison Univ, Sackville, NB E0A 3C0, Canada. [Campana, Lisa M.] Boston Univ, Boston, MA 02215 USA. [Trinder, John; Jordan, Amy S.] Univ Melbourne, Dept Psychol Sci, Melbourne, Vic 3010, Australia. [Nandedkar, Sanjeev] Care Fus SDN, Middleton, WI USA. [David, William S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Saboisky, JP (reprint author), Neurosci Res Australia NeuRA, Barker St, Sydney, NSW 2031, Australia. EM j.saboisky@neura.edu.au RI Eckert, Danny/A-6145-2012; Saboisky, Julian/P-5782-2014; OI Eckert, Danny/0000-0003-3503-2363; Saboisky, Julian/0000-0002-9450-6023; Jordan, Amy/0000-0001-8561-9766 FU NIH [5K24HL093218-02, 5R01HL090897-02, R01 HL085188, P01 HL 095491]; AHA [0840159N] FX Supported by NIH 5K24HL093218-02 and 5R01HL090897-02, AHA 0840159N, NIH R01 HL085188, and P01 HL 095491. NR 63 TC 36 Z9 36 U1 0 U2 9 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2012 VL 185 IS 3 BP 322 EP 329 DI 10.1164/rccm.201106-1058OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 885TF UT WOS:000299803000015 PM 22016445 ER PT J AU Heyworth, BE Carroll, KM Dawson, CK Gill, TJ AF Heyworth, Benton E. Carroll, Kaitlin M. Dawson, Courtney K. Gill, Thomas J. TI Open Lateral Retinacular Closure Surgery for Treatment of Anterolateral Knee Pain and Disability After Arthroscopic Lateral Retinacular Release SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE lateral release; lateral retinaculum; lateral retinacular closure; patellar instability ID MEDIAL SUBLUXATION; CHONDROMALACIA PATELLAE; RECURRENT DISLOCATION; FOLLOW-UP; DIAGNOSIS; RECONSTRUCTION; INJURIES AB Background: Although lateral retinacular release (LR) surgery has historically been one of the most commonly used arthroscopic procedures for the treatment of patellar instability and anterior knee pain, it may be associated with complications and poor functional outcome measures. Purpose: To examine the clinical efficacy of open lateral retinacular closure (LRC), a novel but technically simple procedure in the treatment of disabling anterolateral knee pain, tenderness, and positive medial patellar apprehension testing in patients who have undergone prior arthroscopic LR surgery. Study Design: Case series; Level of evidence, 4. Methods: The records of 22 patients who had previously undergone an arthroscopic LR and underwent a diagnostic arthroscopy and LRC were reviewed. Physical examination findings and symptoms after prior LR surgery, duration between LR and LRC surgeries, and arthroscopic findings immediately before LRC were analyzed. Preoperative and postoperative Lysholm knee scores and activity levels were compared, and subjective satisfaction ratings assessed. Results: Average follow-up after LRC was 3.2 years. Mean preoperative Lysholm knee score was 46.5 (range, 25-90), which improved postoperatively to a mean score of 86 (range, 48-100). Fourteen percent of patients subjectively rated their preoperative function as fair and 86% as poor. Postoperatively, 82% rated themselves as good or excellent and 18% as fair, with all patients improving from the LRC procedure. All patients stated that they would have the procedure again for the same problem. Conclusion: Open LRC provides significant pain relief and improvement in functional knee outcome scores in patients with persistent pain and tenderness at the site of a previous lateral release and a positive medial patellar apprehension test. Lateral release procedures should be considered with caution. For patients with anterolateral knee pain and symptoms of medial patellar instability after lateral release, LRC may provide symptomatic relief and functional improvement. C1 [Heyworth, Benton E.; Carroll, Kaitlin M.; Dawson, Courtney K.; Gill, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Heyworth, BE (reprint author), 300 Longwood Ave,Hunnewell 217, Boston, MA 02115 USA. EM ben-ton.heyworth@childrens.harvard.edu NR 34 TC 11 Z9 12 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD FEB PY 2012 VL 40 IS 2 BP 376 EP 382 DI 10.1177/0363546511428600 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 885LU UT WOS:000299781300015 PM 22138110 ER PT J AU Yeh, H Rand, E AF Yeh, H. Rand, E. TI When Mothers Are Better Than Fathers... SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID MATERNAL MICROCHIMERISM; BILIARY ATRESIA C1 [Yeh, H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Rand, E.] Childrens Hosp Philadelphia, Dept Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA. RP Yeh, H (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM hyeh@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2012 VL 12 IS 2 BP 279 EP 280 DI 10.1111/j.1600-6143.2011.03901.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 883HP UT WOS:000299625200006 PM 22225593 ER PT J AU Song, JJ Ott, HC AF Song, J. J. Ott, H. C. TI Bioartificial Lung Engineering SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE Bioartificial lung; lung transplantation; perfusion decellularization; regenerative medicine; tissue engineering ID EMBRYONIC STEM-CELLS; EPITHELIAL-CELLS; DIFFERENTIATION; TISSUE; TRANSPLANTATION; PROTEIN; INJURY; MICROENVIRONMENT; PROLIFERATION; ENDODERM AB End-stage lung disease is a major health care challenge. Lung transplantation remains the definitive treatment, yet rejection and donor organ shortage limit its broader clinical impact. Engineering bioartificial lung grafts from patient-derived cells could theoretically lead to alternative treatment strategies. Although many challenges on the way to clinical application remain, important early milestones toward translation have been met. Key endodermal progenitors can be derived from patients and expanded in vitro. Advanced culture conditions facilitate the formation of three-dimensional functional tissues from lineage-committed cells. Bioartificial grafts that provide gas exchange have been generated and transplanted into animal models. Looking ahead, current challenges in bioartificial lung engineering include creation of ideal scaffold materials, differentiation and expansion of lung-specific cell populations and full maturation of engineered constructs to provide graft longevity after implantation in vivo. A multidisciplinary collaborative effort will not only bring us closer to the ultimate goal of engineering patient-derived lung grafts, but also generate a series of clinically valuable translational milestones such as airway grafts and disease models. This review summarizes achievements to date, current challenges and ongoing research in bioartificial lung engineering. C1 [Song, J. J.; Ott, H. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg,Dept Surg, Boston, MA 02115 USA. [Ott, H. C.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Ott, HC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg,Dept Surg, Boston, MA 02115 USA. EM hott@partners.org RI Phatak, Sai/C-5725-2012 NR 38 TC 18 Z9 19 U1 1 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2012 VL 12 IS 2 BP 283 EP 288 DI 10.1111/j.1600-6143.2011.03808.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 883HP UT WOS:000299625200008 PM 22026560 ER PT J AU Hirohashi, T Chase, CM Della Pelle, P Sebastian, D Alessandrini, A Madsen, JC Russell, PS Colvin, RB AF Hirohashi, T. Chase, C. M. Della Pelle, P. Sebastian, D. Alessandrini, A. Madsen, J. C. Russell, P. S. Colvin, R. B. TI A Novel Pathway of Chronic Allograft Rejection Mediated by NK Cells and Alloantibody SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Antibody-mediated rejection; chronic allograft vasculopathy; Fc receptors; heart transplantation; NK cells ID CLASS-I ANTIBODY; FACTOR RECEPTOR EXPRESSION; MURINE CARDIAC ALLOGRAFTS; NATURAL-KILLER-CELLS; SMOOTH-MUSCLE-CELLS; MHC CLASS-I; ENDOTHELIAL-CELLS; TRANSPLANT ARTERIOPATHY; LUNG-TRANSPLANTATION; MIXED CHIMERISM AB Chronic allograft vasculopathy (CAV) in murine heart allografts can be elicited by adoptive transfer of donor specific antibody (DSA) to class I MHC antigens and is independent of complement. Here we address the mechanism by which DSA causes CAV. B6.RAG1-/- or B6.RAG1-/-C3-/- (H-2b) mice received B10.BR (H-2k) heart allografts and repeated doses of IgG2a, IgG1 or F(ab)2 fragments of IgG2a DSA (anti-H-2k). Intact DSA regularly elicited markedly stenotic CAV in recipients over 28 days. In contrast, depletion of NK cells with anti-NK1.1 reduced significantly DSA-induced CAV, as judged morphometrically. Recipients genetically deficient in mature NK cells (?-chain knock out) also showed decreased severity of DSA-induced CAV. Direct NK reactivity to the graft was not necessary. F(ab)2 DSA fragments, even at doses twofold higher than intact DSA, were inactive. Graft microvascular endothelial cells responded to DSA in vivo by increased expression of phospho-extracellular signal-regulated kinase (pERK), a response not elicited by F(ab)2 DSA. We conclude that antibody mediates CAV through NK cells, by an Fc dependent manner. This new pathway adds to the possible mechanisms of chronic rejection and may relate to the recently described C4d-negative chronic antibody-mediated rejection in humans. C1 [Della Pelle, P.; Sebastian, D.; Colvin, R. B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hirohashi, T.; Chase, C. M.; Alessandrini, A.; Madsen, J. C.; Russell, P. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplantat, Boston, MA USA. [Hirohashi, T.; Chase, C. M.; Alessandrini, A.; Madsen, J. C.; Russell, P. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Surg Div,Dept Surg, Boston, MA USA. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM colvin@helix.mgh.harvard.edu FU Roche Organ Transplant Research Foundation; NIH [RO1 HL071932]; American Society of Transplantation FX This work was supported in part by the Roche Organ Transplant Research Foundation (RBC), NIH grant RO1 HL071932 (JCM) and by a Basic Science Grant from the American Society of Transplantation (TH). NR 42 TC 88 Z9 89 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2012 VL 12 IS 2 BP 313 EP 321 DI 10.1111/j.1600-6143.2011.03836.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 883HP UT WOS:000299625200012 PM 22070565 ER PT J AU Yamada, Y Boskovic, S Aoyama, A Murakami, T Putheti, P Smith, RN Ochiai, T Nadazdin, O Koyama, I Boenisch, O Najafian, N Bhasin, MK Colvin, RB Madsen, JC Strom, TB Sachs, DH Benichou, G Cosimi, AB Kawai, T AF Yamada, Y. Boskovic, S. Aoyama, A. Murakami, T. Putheti, P. Smith, R. N. Ochiai, T. Nadazdin, O. Koyama, I. Boenisch, O. Najafian, N. Bhasin, M. K. Colvin, R. B. Madsen, J. C. Strom, T. B. Sachs, D. H. Benichou, G. Cosimi, A. B. Kawai, T. TI Overcoming Memory T-Cell Responses for Induction of Delayed Tolerance in Nonhuman Primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Donor bone marrow transplantation; kidney transplantation; memory T cells; mixed chimerism; nonhuman primates; tolerance ID RENAL-ALLOGRAFT TOLERANCE; TOLL-LIKE RECEPTORS; TRANSPLANTATION TOLERANCE; HETEROLOGOUS IMMUNITY; ORGAN-TRANSPLANTATION; MONOCLONAL-ANTIBODY; CYNOMOLGUS MACAQUES; CHIMERISM; DEPLETION; BARRIER AB The presence of alloreactive memory T cells is a major barrier for induction of tolerance in primates. In theory, delaying conditioning for tolerance induction until after organ transplantation could further decrease the efficacy of the regimen, since preexisting alloreactive memory T cells might be stimulated by the transplanted organ. Here, we show that such delayed tolerance can be induced in nonhuman primates through the mixed chimerism approach, if specific modifications to overcome/avoid donor-specific memory T-cell responses are provided. These modifications include adequate depletion of CD8+ memory T cells and timing of donor bone marrow administration to minimize levels of proinflammatory cytokines. Using this modified approach, mixed chimerism was induced successfully in 11 of 13 recipients of previously placed renal allografts and long-term survival without immunosuppression could be achieved in at least 6 of these 11 animals. C1 [Yamada, Y.; Boskovic, S.; Aoyama, A.; Murakami, T.; Ochiai, T.; Nadazdin, O.; Koyama, I.; Madsen, J. C.; Benichou, G.; Cosimi, A. B.; Kawai, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA 02115 USA. [Putheti, P.; Bhasin, M. K.; Strom, T. B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Transplant Inst, Boston, MA 02215 USA. [Smith, R. N.; Colvin, R. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Boenisch, O.; Najafian, N.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. [Sachs, D. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Biol Res Ctr, Boston, MA USA. RP Kawai, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA 02115 USA. EM tkawai@partners.org FU NHL-BI [5U19DK080652-02]; NIH-NIAID; NIH/NIAID [5R01 AI50987-03]; NIH [R00000000008108]; [POI-HL18646]; [ROIA137692] FX This study was supported in part by 5U19DK080652-02 NHL-BI, POI-HL18646, NIH-NIAID, ROIA137692 and NIH/NIAID 5R01 AI50987-03 and NIH R00000000008108. NR 40 TC 35 Z9 36 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2012 VL 12 IS 2 BP 330 EP 340 DI 10.1111/j.1600-6143.2011.03795.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 883HP UT WOS:000299625200014 PM 22053723 ER PT J AU Brown, JA Min, JH Staropoli, JF Collin, E Bi, S Feng, X Barone, R Cao, Y O'Malley, L Xin, WN Mullen, TE Sims, KB AF Brown, Jeffrey A. Min, Jionghong Staropoli, John F. Collin, Elisa Bi, Stephen Feng, Xin Barone, Rosemary Cao, Yi O'Malley, Lei Xin, Winnie Mullen, Thomas E. Sims, Katherine B. TI SOD1, ANG, TARDBP and FUS mutations in amyotrophic lateral sclerosis: A United States clinical testing lab experience SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE Amyotrophic lateral sclerosis (ALS); superoxide dismutase 1 (SOD1); angiogenin (ANG); TAR DNA binding protein (TARDBP); FUS protein (FUS) ID SUPEROXIDE-DISMUTASE GENE; EXPRESSION; PATHOLOGY; DISEASE AB SOD1, ANG, TARDBP and FUS mutations have been associated with amyotrophic lateral sclerosis (ALS). Our goal was to extend molecular genetic analysis to newly identified ALS genetic loci and to determine the frequency of mutations, distribution of disease genes, and variant spectrum of these genes in a large United States ALS-phenotype cohort. We screened 1220 probands with an ALS phenotype, referred originally for SOD1 molecular genetic analysis. 1128 SOD1-negative probands were screened for ANG, and 277 and 223 SOD1- and ANG-negative samples were screened for TARDBP and FUS, respectively. One hundred additional probands were specifically screened only for FUS exon 15. We identified a total of 36 different SOD1 mutations, including three novel mutations, in 92 probands. ANG screening identified three mutations, including two novel mutations, and TARDBP screening identified two previously reported TARDBP mutations. We also identified four mutations in FUS, including the reported FUS in-frame deletion, c.430_447del, p.Gly144_Tyr149del, in a patient with inclusion body myositis, and two known FUS missense mutations. From this study, we estimate frequencies for SOD1, ANG, TARDBP and FUS mutations, in this United States cohort, to be 7.5%, 0.71%, 0.72% and 1.9%, respectively. In conclusion, we identify novel variants in SOD1, ANG, TARDBP and FUS, and expand the FUS-associated clinicopathologic phenotype. C1 [Brown, Jeffrey A.; Min, Jionghong; Staropoli, John F.; Collin, Elisa; Bi, Stephen; Feng, Xin; Barone, Rosemary; Cao, Yi; O'Malley, Lei; Xin, Winnie; Mullen, Thomas E.; Sims, Katherine B.] Massachusetts Gen Hosp, Neurogenet DNA Diagnost Lab, Ctr Human Genet Res, Boston, MA 02114 USA. [Xin, Winnie; Sims, Katherine B.] Harvard Univ, Sch Med, Boston, MA USA. [Xin, Winnie; Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Sims, KB (reprint author), MGH Neurogenet DNA Diagnost Lab, Simches Res Bldg 5-300,185 Cambridge St,Room 5238, Boston, MA 02114 USA. EM ksims@partners.org NR 24 TC 28 Z9 29 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PD FEB PY 2012 VL 13 IS 2 BP 217 EP 222 DI 10.3109/17482968.2011.643899 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 884IY UT WOS:000299699400007 PM 22292843 ER PT J AU Zhang, B Tian, M Zhen, Y Yue, Y Sherman, J Zheng, H Li, SR Tanzi, RE Marcantonio, ER Xie, ZC AF Zhang, Bin Tian, Ming Zhen, Yu Yue, Yun Sherman, Janet Zheng, Hui Li, Shuren Tanzi, Rudolph E. Marcantonio, Edward R. Xie, Zhongcong TI The Effects of isoflurane and Desflurane on Cognitive Function in Humans SO ANESTHESIA AND ANALGESIA LA English DT Article ID ARTERY-BYPASS-SURGERY; BETA-PROTEIN-LEVELS; POSTOPERATIVE DELIRIUM; NONCARDIAC SURGERY; GENERAL-ANESTHESIA; NEUROCOGNITIVE FUNCTION; CASPASE ACTIVATION; ELDERLY-PATIENTS; HIP FRACTURE; OLDER-ADULTS AB BACKGROUND: The etiology of postoperative cognitive decline (POCD) remains to be determined. Anesthetic isoflurane, but not desflurane, may induce neurotoxicity. However, the functional consequences of these effects have not been assessed. We therefore performed a pilot study to determine the effects of isoflurane and desflurane on cognitive function in humans. METHODS: The subjects included patients who had lower extremity or abdominal surgery under spinal anesthesia alone (S, n = 15), spinal plus desflurane anesthesia (SD, n = 15), or spinal plus isoflurane anesthesia (SI, n = 15) by randomization. Each of the subjects received cognitive tests immediately before and 1 week after anesthesia and surgery administered by an investigator who was blinded to the anesthesia regimen. POCD was defined using the scores from each of these tests. RESULTS: We studied 45 subjects, 24 males and 21 females. The mean age of the subjects was 69.0 +/- 1.9 years. There was no significant difference in age and other characteristics among the treatment arms. The mean number of cognitive function declines in the S, SD, and SI groups was 1.13, 1.07, and 1.40, respectively. POCD incidence after SI (27%), but not SD (0%), anesthesia was higher than that after S (0%), P = 0.028 (3-way comparison). CONCLUSION: These findings from our pilot study suggest that isoflurane and desflurane may have different effects on postoperative cognitive function, and additional studies with a larger sample size and longer times of follow-up testing are needed. (Anesth Analg 2012;114:410-5) C1 [Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. [Zhang, Bin; Tian, Ming; Zhen, Yu] Capital Med Univ, Beijing Friendship Hosp, Dept Anesthesia, Beijing, Peoples R China. [Sherman, Janet] Massachusetts Gen Hosp, Psychol Assessment Ctr, Charlestown, MA USA. [Yue, Yun] Massachusetts Gen Hosp, Ctr Biostat, Charlestown, MA USA. [Tanzi, Rudolph E.] Massachusetts Gen Hosp, Genet & Aging Res Unit, Dept Neurol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care & Gerontol, Dept Med, Boston, MA 02215 USA. [Yue, Yun] Capital Med Univ, Beijing Chaoyang Hosp, Dept Anesthesia, Beijing, Peoples R China. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@partners.org FU Beijing science and technology development plan of the education committee [KM200910025016]; National Science Foundation [NSF30928026] FX This research was supported by Beijing science and technology development plan of the education committee, KM200910025016 (to M.T.), and National Science Foundation Oversea young scholar collaboration research award NSF30928026 (to Y.Y. and Z.X.). NR 42 TC 30 Z9 40 U1 5 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 2012 VL 114 IS 2 BP 410 EP 415 DI 10.1213/ANE.06013e3182362602 PG 6 WC Anesthesiology SC Anesthesiology GA 881MQ UT WOS:000299491200021 PM 22075020 ER PT J AU Bateman, BT Olbrecht, VA Berman, MF Minehart, RD Schwamm, LH Leffert, LR AF Bateman, Brian T. Olbrecht, Vanessa A. Berman, Mitchell F. Minehart, Rebecca D. Schwamm, Lee H. Leffert, Lisa R. TI Peripartum Subarachnoid Hemorrhage Nationwide Data and Institutional Experience SO ANESTHESIOLOGY LA English DT Article ID OF-THE-LITERATURE; RISK-FACTORS; INTRACRANIAL HEMORRHAGE; COMPLICATING PREGNANCY; BLOOD-PRESSURE; STROKE; PUERPERIUM; ECLAMPSIA; MALFORMATIONS; HYPERTENSION AB Background: Subarachnoid hemorrhage (SAH) in pregnancy occurs because of a variety of etiologies, which range from ruptured aneurysms to benign venous bleeding. The more malignant etiologies represent an important cause of maternal morbidity and mortality. We sought to investigate the epidemiology and mechanisms of pregnancy-related SAH. Methods: Using the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, we extracted pregnancy-related admissions for women ages 15-44 from 1995-2008 and identified admissions complicated by SAH. Logistic regression identified independent predictors of SAH. Outcomes and risk factors were then compared with age-matched, nonpregnant women with SAH. We also analyzed our institution's experience with pregnancy-related SAH. Results: There were 639 cases (5.8 per 100,000 deliveries) of pregnancy-related SAH in the cohort during the study period; SAH was associated with 4.1% of all pregnancy-related in-hospital deaths. More than half of the SAH cases occurred postpartum. Advancing age, African-American race, Hispanic ethnicity, hypertensive disorders: coagulopathy, tobacco, drug or alcohol abuse, intracranial venous thrombosis, sickle cell disease, and hypercoagulability were independent risk factors for pregnancy-related SAH. Compared with SAH in nonpregnant controls, pregnancy-related SAH had lower clipping/coiling rates (12.7% vs. 44.5%, P < 0.001). We identified 12 cases of pregnancy-related SAH in our hospital, the majority of which presented postpartum and with severe headache. Conclusion: SAN during pregnancy results from a range of etiologies, and is less likely to be because of a cerebral aneurysm than SAH occurring in the nonpregnant patient. Peripartum SAH frequently occurs in the setting of hypertensive disorders. C1 [Bateman, Brian T.; Olbrecht, Vanessa A.; Minehart, Rebecca D.; Leffert, Lisa R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Bateman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM bbateman@partners.org OI Minehart, Rebecca/0000-0001-8504-8967; Schwamm, Lee/0000-0003-0592-9145 NR 36 TC 25 Z9 29 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD FEB PY 2012 VL 116 IS 2 BP 324 EP 333 DI 10.1097/ALN.0b013e3182410b22 PG 10 WC Anesthesiology SC Anesthesiology GA 883WS UT WOS:000299666200012 PM 22166951 ER PT J AU Munzone, E Curigliano, G Burstein, HJ Winer, EP Goldhirsch, A AF Munzone, E. Curigliano, G. Burstein, H. J. Winer, E. P. Goldhirsch, A. TI CMF revisited in the 21st century SO ANNALS OF ONCOLOGY LA English DT Review DE adjuvant chemotherapy; alkylating agents; breast cancer; classical CMF; triple-negative; tumor heterogeneity ID NEGATIVE BREAST-CANCER; SURGICAL ADJUVANT BREAST; 2 RANDOMIZED-TRIALS; COMBINATION CHEMOTHERAPY; SEQUENTIAL METHOTREXATE; CLINICAL-TRIALS; INTRAVENOUS CMF; 1ST REPORT; FOLLOW-UP; HIGH-RISK AB Over the last 35 years, classical CMF (combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil) has been a milestone in the adjuvant treatment of women with breast cancer. However, after an early burst of success lasted just over 10 years, classical CMF has been supplanted by 'third-generation' regimens containing taxanes and anthracyclines. Questions have been raised in the past years concerning the true effectiveness of adjuvant CMF for specific subgroups of patients and particularly, recent retrospective data support the fact that the CMF might have a role in the treatment of patients with triple-negative breast cancer. One possible justification for supporting this role of CMF may be sought in the mechanism of action of drugs used in the regimen, as triple-negative cells may be sensitive to alkylating agents that cause double-strand breaks in DNA. The lesson learned from the CMF could lead us to identify new combinations of drugs that could include the optimal chemotherapy backbone for triple-negative breast cancer such as platinum compounds or alkylating agents or Poly (ADP-ribose) polymerase inhibitors. In conclusion, although we have learned a lot from the use of CMF, many questions are still open and hopefully stimulate our thinking, as clinicians, leading us to find new and more effective ways to treat breast cancer. C1 [Munzone, E.; Curigliano, G.; Goldhirsch, A.] European Inst Oncol, Div Med Oncol, I-20141 Milan, Italy. [Burstein, H. J.; Winer, E. P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Breast Oncol Ctr, Boston, MA 02115 USA. RP Munzone, E (reprint author), European Inst Oncol, Div Med Oncol, Via Ripamonti 435, I-20141 Milan, Italy. EM elisabetta.munzone@ieo.it RI Munzone, Elisabetta/G-8848-2011 NR 59 TC 12 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2012 VL 23 IS 2 BP 305 EP U278 DI 10.1093/annonc/mdr309 PG 7 WC Oncology SC Oncology GA 884YI UT WOS:000299744400005 PM 21715566 ER PT J AU Miller, KD O'Neill, A Perez, EA Seidman, AD Sledge, GW AF Miller, K. D. O'Neill, A. Perez, E. A. Seidman, A. D. Sledge, G. W. TI A phase II pilot trial incorporating bevacizumab into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node positive breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group SO ANNALS OF ONCOLOGY LA English DT Article DE angiogenesis; breast cancer; cardiomyopathy; clinical trial; vascular endothelial growth factor ID CARDIAC SAFETY; GROWTH-FACTOR; CHEMOTHERAPY; TRASTUZUMAB; STATISTICS; THERAPY; WOMEN AB Background: E2104 was designed to evaluate the safety of two different strategies incorporating bevacizumab into anthracycline-containing adjuvant therapy as a precursor to a definitive randomized phase III trial. Patients and methods: Patients were sequentially assigned to one of two treatment arms. In addition to dose-dense doxorubicin and cyclophosphamide followed by paclitaxel (Taxol) (ddAC -> T), all patients receivedbevacizumab (10 mg/kg every 2 weeks x 26) initiated either concurrently with AC (Arm A: ddBAC -> BT -> B) or with paclitaxel (Arm B: ddAC -> BT -> B). The primary end point was incidence of clinically apparent cardiac dysfunction (CHF). Results: Patients enrolled were 226 in number (Arm A 104, Arm B 122). Grade 3 hypertension, thrombosis, proteinuria and hemorrhage were reported for 12, 2, 2 and <1% of patients, respectively. Two patients developed grade 3 or more cerebrovascular ischemia. Three patients in each arm developed CHF. There was no significant difference between arms in the proportion of patients with an absolute decrease in left ventricular ejection fraction of >15% or >10% to below the lower limit of normal post AC or post bevacizumab. Conclusions: Incorporation of bevacizumab into anthracycline-containing adjuvant therapy does not result in prohibitive cardiac toxicity. The definitive phase III trial (E5103) was activated with systematic and extensive cardiac monitoring to define the true impact of bevacizumab on cardiac function. C1 [Miller, K. D.; Sledge, G. W.] Indiana Univ, Dept Med, Div Hematol & Oncol, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA. [O'Neill, A.] Eastern Cooperat Oncol Grp, Boston, MA USA. [O'Neill, A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Perez, E. A.] Mayo Clin, Dept Med, Div Hematol Oncol, Ctr Canc, Jacksonville, FL USA. [Seidman, A. D.] Cornell Univ, Breast Canc Med Serv, Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Seidman, A. D.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. RP Miller, KD (reprint author), Indiana Univ, Dept Med, Div Hematol & Oncol, Melvin & Bren Simon Canc Ctr, Indiana Canc Pavil,535 Barnhill Dr,RT473, Indianapolis, IN 46202 USA. EM kathmill@iupui.edu FU National Cancer Institute, National Institutes of Health and the Department of Health and Human Services [CA23318, CA66636, CA21115, CA49883, CA25224, CA77651]; Genentech/Roche; Genentech FX Supported in part by Public Health Service Grants (CA23318, CA66636, CA21115, CA49883, CA25224, and CA77651) from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services.; KDM and ADS are consultants to and receive research funding from Genentech/Roche. EAP receives research funding from Genentech/Roche. The remaining authors have no declared conflicts of interest. E2104 was conducted under a corporate research and development agreement between Genentech and the NCI. Genentech provided bevacizumab and partial funding but did not participate in study design or data collection. Analysis was conducted by ECOG. The lead author made the decision to publish and wrote the manuscript, which was reviewed by all authors and submitted to NCI and Genentech for comment. The authors vouch for the completeness and accuracy of the data. NR 30 TC 10 Z9 10 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2012 VL 23 IS 2 BP 331 EP 337 DI 10.1093/annonc/mdr344 PG 7 WC Oncology SC Oncology GA 884YI UT WOS:000299744400009 PM 21821545 ER PT J AU Ojha, RP Thertulien, R AF Ojha, R. P. Thertulien, R. TI Second malignancies among Waldenstrom macroglobulinemia patients: small samples and sparse data SO ANNALS OF ONCOLOGY LA English DT Letter C1 [Ojha, R. P.] Harvard Canc Ctr, Div Populat Sci, Dana Farber Canc Inst, Boston, MA USA. [Thertulien, R.] Canc Ctr N Carolina, Asheville, NC USA. RP Ojha, RP (reprint author), Harvard Canc Ctr, Div Populat Sci, Dana Farber Canc Inst, Boston, MA USA. EM rohit_ojha@dfci.harvard.edu OI Ojha, Rohit/0000-0003-0595-8990 NR 4 TC 7 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2012 VL 23 IS 2 BP 542 EP U275 DI 10.1093/annonc/mdr537 PG 2 WC Oncology SC Oncology GA 884YI UT WOS:000299744400039 PM 22100692 ER PT J AU Merkow, RP Bilimoria, KY McCarter, MD Chow, WB Ko, CY Bentrem, DJ AF Merkow, Ryan P. Bilimoria, Karl Y. McCarter, Martin D. Chow, Warren B. Ko, Clifford Y. Bentrem, David J. TI Use of Multimodality Neoadjuvant Therapy for Esophageal Cancer in the United States: Assessment of 987 Hospitals SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID PHASE-III TRIAL; PREOPERATIVE CHEMORADIOTHERAPY; PERIOPERATIVE CHEMOTHERAPY; RESECTABLE CANCER; SURGERY; METAANALYSIS; CARCINOMA; CHEMORADIATION; ADENOCARCINOMA; CISPLATIN AB Consensus guidelines recommend neoadjuvant therapy in locally advanced esophageal cancer; however, whether this recommendation has been widely adopted is unknown. Therefore, we evaluated the utilization of neoadjuvant therapy in esophageal cancer and its association with outcomes in the United States. From the National Cancer Data Base all patients with middle and lower third clinical stage I-III esophageal cancers who underwent surgical resection were identified (1998-2007). Multivariable regression models were developed to identify predictors of neoadjuvant therapy use and associated outcomes. We identified 8562 patients who underwent surgical resection for esophageal cancer. In nonmetastatic locally advanced tumors, neoadjuvant therapy use increased (stage II 47.9% to 72.5%; stage III 51.0% to 90.1%; P < 0.001). On multivariable analysis, factors associated with the decreased use of neoadjuvant therapy for stage II and III disease were age a parts per thousand yen75 years, Medicare insurance coverage, Charlson score a parts per thousand yen2, stage II (vs. III) disease, and geographic region. Patients with stage II and III disease who underwent neoadjuvant therapy had a lower risk of positive lymph nodes (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.35-0.55) and positive surgical margins (OR 0.51, 95% CI 0.38-0.69). Thirty-day postoperative mortality rates were not significantly affected by neoadjuvant therapy (OR 0.90, 95% CI 0.66-1.24). A pathologic complete response was observed in 10.8% of patients. The only factor that was predictive of pathologic complete response was squamous cell tumor histology (OR 2.14, 95% CI 1.52-3.02). In surgically treated patients, the use of neoadjuvant trimodal therapy has increased in the past decade; however, opportunities exist to improve adherence to national guidelines. C1 [Merkow, Ryan P.; Bentrem, David J.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Merkow, Ryan P.; McCarter, Martin D.] Univ Colorado, Sch Med, Dept Surg, Aurora, CO USA. [Bilimoria, Karl Y.] Univ Texas MD Anderson Canc Ctr, Dept Surg, Houston, TX 77030 USA. [Chow, Warren B.; Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Chow, Warren B.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bentrem, David J.] Jesse Brown VA Med Ctr, Dept Surg, Chicago, IL USA. RP Merkow, RP (reprint author), Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. EM dbentrem@nmff.org FU Health Services Research Division, Department of Veterans Affairs FX D.J.B. is supported by a Career Development Award from the Health Services Research Division, Department of Veterans Affairs. NR 40 TC 22 Z9 23 U1 1 U2 2 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 FEB PY 2012 VL 19 IS 2 BP 357 EP 364 DI 10.1245/s10434-011-1945-3 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 881KO UT WOS:000299483200004 PM 21769460 ER PT J AU Ikonomidis, JS Ruddy, JM Benton, SM Arroyo, J Brinsa, TA Stroud, RE Zeeshan, A Bavaria, JE Gorman, JH Gorman, RC Spinale, FG Jones, JA AF Ikonomidis, John S. Ruddy, Jean Marie Benton, Stewart M., Jr. Arroyo, Jazmine Brinsa, Theresa A. Stroud, Robert E. Zeeshan, Ahmed Bavaria, Joseph E. Gorman, Joseph H., III Gorman, Robert C. Spinale, Francis G. Jones, Jeffrey A. TI Aortic Dilatation With Bicuspid Aortic Valves: Cusp Fusion Correlates to Matrix Metalloproteinases and Inhibitors INVITED COMMENTARY SO ANNALS OF THORACIC SURGERY LA English DT Article ID ASCENDING AORTA; NEUTROPHIL COLLAGENASE; PROTEIN EXPRESSION; TISSUE INHIBITORS; ANEURYSMS; PATTERNS; DISSECTIONS; PROTEOLYSIS AB Background. Congenital bicuspid aortic valves (BAVs) result from fusion of 2 valve cusps, resulting in left-noncoronary (L-N), right-left (R-L), and right-noncoronary (R-N) morphologic presentations. BAVs predispose to ascending thoracic aortic aneurysms (ATAAs). This study hypothesized that ATAAs with each BAV morphologic group possess unique signatures of matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of metalloproteinases (TIMPs). Methods. Ascending thoracic aortic aneurysm tissue from 46 patients with BAVs was examined for MMP/TIMP abundance, and global MMP activity was compared with normal aortic specimens (n = 15). Proteolytic balance was calculated as the ratio of MMP abundance to a composite TIMP score. Results were stratified by valve morphologic group (L-N [n = 6], R-L [n = 31], and R-N [n = 9]). Results. The BAV specimens (p < 0.05 versus normal aorta, 100%) displayed elevated global MMP activity (273% +/- 63%), MMP-9 (263% +/- 47%), and decreased MMP-7 (56% +/- 10%), MMP-8 (58% +/- 11%), TIMP-1 (63% +/- 7%), and TIMP-4 (38% +/- 3%). The R-L group showed increased global MMP activity (286% +/- 89%) and MMP-9 (267% +/- 55%) with reduced MMP-7 (45% +/- 7%), MMP-8 (68% +/- 15%), TIMP-1 (58% +/- 7%), and TIMP-4 (35% +/- 3%). The L-N group showed elevated global MMP activity (284% +/- 71%) and decreased MMP-8 (37% +/- 17%) and TIMP-4 (48% +/- 14) activity. In the R-N group, MMP-7 (46% +/- 13%) and MMP-8 (36% +/- 17%) and TIMP-1 (59% +/- 10%) and TIMP-4 (42% +/- 5%) were decreased. The R-L group demonstrated an increased proteolytic balance for MMP-1, MMP-9, and MMP-12 relative to L-N and R-N. Conclusions. Each BAV morphologic group possesses a unique signature of MMPs and TIMPs. MMP/TIMP score ratios suggest that the R-L group may be more aggressive, justifying earlier surgical intervention. (Ann Thorac Surg 2012;93:457-64) (C) 2012 by The Society of Thoracic Surgeons C1 [Ikonomidis, John S.] Med Univ S Carolina, Div Cardiothorac Surg, S Carolina Heart Valve Ctr, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. Univ Penn, Div Cardiothorac Surg, Philadelphia, PA 19104 USA. RP Ikonomidis, JS (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, S Carolina Heart Valve Ctr, 25 Courtenay Dr,Ste 7030, Charleston, SC 29425 USA. EM ctsxresearch@musc.edu FU NIH/NHLBI [R21 HL089170] FX This study was supported by NIH/NHLBI grant R21 HL089170. NR 37 TC 29 Z9 30 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2012 VL 93 IS 2 BP 457 EP 464 DI 10.1016/j.athoracsur.2011.09.057 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 882CX UT WOS:000299540200025 PM 22206960 ER PT J AU Moskowitz, SM Brannon, MK Dasgupta, N Pier, M Sgambati, N Miller, AK Selgrade, SE Miller, SI Denton, M Conway, SP Johansen, HK Hoiby, N AF Moskowitz, Samuel M. Brannon, Mark K. Dasgupta, Nandini Pier, Miyuki Sgambati, Nicole Miller, Amanda K. Selgrade, Sara E. Miller, Samuel I. Denton, Miles Conway, Steven P. Johansen, Helle K. Hoiby, Niels TI PmrB Mutations Promote Polymyxin Resistance of Pseudomonas aeruginosa Isolated from Colistin-Treated Cystic Fibrosis Patients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID 2-COMPONENT REGULATORY SYSTEM; CATIONIC ANTIMICROBIAL PEPTIDES; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; LIPID-A; ACINETOBACTER-BAUMANNII; SALMONELLA-TYPHIMURIUM; B RESISTANCE; PHOP-PHOQ; INFECTION AB Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of colistin (polymyxin E) resistance in laboratory strains and clinical isolates of this organism (MICs of 8 to 64 mg/liter). To explore the role of PmrAB in high-level clinical polymyxin resistance, P. aeruginosa isolates from chronically colistin-treated cystic fibrosis patients, most with colistin MICs of >512 mg/liter, were analyzed. These cystic fibrosis isolates contained probable gain-of-function pmrB alleles that conferred polymyxin resistance to strains with a wild-type or pmrAB deletion background. Double mutant pmrB alleles that contained mutations in both the periplasmic and dimerization-phosphotransferase domains markedly augmented polymyxin resistance. Expression of mutant pmrB alleles induced transcription from the promoter of the arnB operon and stimulated addition of 4-amino-L-arabinose to lipid A, consistent with the known role of this lipid A modification in polymyxin resistance. For some highly polymyxin-resistant clinical isolates, repeated passage without antibiotic selection pressure resulted in loss of resistance, suggesting that secondary suppressors occur at a relatively high frequency and account for the instability of this phenotype. These results indicate that pmrB gain-of-function mutations can contribute to high-level polymyxin resistance in clinical strains of P. aeruginosa. C1 [Moskowitz, Samuel M.; Dasgupta, Nandini; Sgambati, Nicole] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Moskowitz, Samuel M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Moskowitz, Samuel M.; Brannon, Mark K.; Pier, Miyuki; Miller, Amanda K.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Selgrade, Sara E.; Miller, Samuel I.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. [Miller, Samuel I.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Miller, Samuel I.] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. [Denton, Miles] Leeds Teaching Hosp NHS Trust, Dept Microbiol, Leeds, W Yorkshire, England. [Conway, Steven P.] Leeds Teaching Hosp NHS Trust, Dept Pediat, Leeds, W Yorkshire, England. [Johansen, Helle K.; Hoiby, Niels] Univ Copenhagen, Rigshosp, Copenhagen CF Ctr, Dept Clin Microbiol, DK-2100 Copenhagen, Denmark. RP Moskowitz, SM (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. EM smoskowitz@partners.org FU National Heart, Lung, and Blood Institute [K08HL067903]; National Institute of Allergy and Infectious Diseases [R01AI067653, R01AI030479]; CF Foundation [MOSKOW01A1] FX This work was supported by Public Health Service grant K08HL067903 to S.M.M. from the National Heart, Lung, and Blood Institute, grant R01AI067653 to S.M.M. from the National Institute of Allergy and Infectious Diseases, and grant R01AI030479 to S.I.M. from the National Institute of Allergy and Infectious Diseases. This work was also supported by grant MOSKOW01A1 to S.M.M. from the CF Foundation. NR 60 TC 44 Z9 44 U1 2 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2012 VL 56 IS 2 BP 1019 EP 1030 DI 10.1128/AAC.05829-11 PG 12 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 883TX UT WOS:000299658900057 PM 22106224 ER PT J AU Rosenbaum, JT Davey, MP AF Rosenbaum, James T. Davey, Michael P. TI The intestinal microbiome in ankylosing spondylitis: comment on the article by Rosenbaum and Davey Reply SO ARTHRITIS AND RHEUMATISM LA English DT Letter C1 [Rosenbaum, James T.; Davey, Michael P.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Davey, Michael P.] Portland VA Med Ctr, Portland, OR USA. RP Rosenbaum, JT (reprint author), Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD FEB PY 2012 VL 64 IS 2 BP 598 EP 598 DI 10.1002/art.33405 PG 1 WC Rheumatology SC Rheumatology GA 883HU UT WOS:000299625700041 ER PT J AU Tomasson, G Boers, M Walsh, M LaValley, M Cuthbertson, D Carette, S Davis, JC Hoffman, GS Khalidi, NA Langford, CA McAlear, CA McCune, WJ Monach, PA Seo, P Specks, U Spiera, R St Clair, EW Stone, JH Ytterberg, SR Merkel, PA AF Tomasson, Gunnar Boers, Maarten Walsh, Michael LaValley, Michael Cuthbertson, David Carette, Simon Davis, John C. Hoffman, Gary S. Khalidi, Nader A. Langford, Carol A. McAlear, Carol A. McCune, W. Joseph Monach, Paul A. Seo, Philip Specks, Ulrich Spiera, Robert St. Clair, E. William Stone, John H. Ytterberg, Steven R. Merkel, Peter A. TI Assessment of health-related quality of life as an outcome measure in granulomatosis with polyangiitis (Wegener's) SO ARTHRITIS CARE & RESEARCH LA English DT Article ID ANTIBODY-ASSOCIATED VASCULITIS; ANCA-ASSOCIATED VASCULITIS; ETANERCEPT TRIAL WGET; RHEUMATOID-ARTHRITIS; RANDOMIZED-TRIAL; CORE SET; CLINICAL-TRIALS; ACTIVITY SCORE; SURVEY SF-36; CYCLOPHOSPHAMIDE AB Objective To assess a generic measure of health-related quality of life (HRQOL) as an outcome measure in granulomatosis with polyangiitis (Wegener's) (GPA). Methods. Subjects were participants in the Wegener's Granulomatosis Etanercept Trial (WGET) or the Vasculitis Clinical Research Consortium Longitudinal Study (VCRC-LS). HRQOL was assessed with the Short Form 36 (SF-36) health survey that includes physical and mental component summary scores (PCS and MCS, respectively). Disease activity was assessed with the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG). Results. The data from 180 subjects in the WGET (median followup 2.3 years, mean number of visits 10) and 237 subjects in the VCRC-LS (median followup 2.0 years, mean number of visits 8) were analyzed. A 1 unit increase in the BVAS/ WG corresponded to a 1.15 unit (95% confidence interval [ 95% CI] 1.02, 1.29) decrease for the PCS and a 0.93 (95% CI 0.78, 1.07) decrease for the MCS in the WGET, and to a 1.16 unit decrease for the PCS (95% CI 0.94, 1.39) and a 0.79 unit decrease for the MCS (95% CI 0.51, 1.39) in the VCRC-LS. In both arms of the WGET study, SF-36 measures improved rapidly during the first 6 weeks of treatment followed by gradual improvement among patients achieving sustained remission (0.5 improvement in PCS per 3 months), but worsened slightly (0.03 decrease in PCS every 3 months) among patients not achieving sustained remission (P = 0.005). Conclusion. HRQOL, as measured by the SF-36, is reduced among patients with GPA. SF-36 measures are modestly associated with other disease outcomes and discriminate between disease states of importance in GPA. C1 [Merkel, Peter A.] Boston Univ, Sch Med, Rheumatol Sect, Boston, MA 02118 USA. [Boers, Maarten] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Walsh, Michael; Khalidi, Nader A.] McMaster Univ, Hamilton, ON, Canada. [Cuthbertson, David] Univ S Florida, Tampa, FL USA. [Carette, Simon] Univ Toronto, Toronto, ON, Canada. [Davis, John C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hoffman, Gary S.; Langford, Carol A.] Cleveland Clin, Cleveland, OH 44106 USA. [McCune, W. Joseph] Univ Michigan, Ann Arbor, MI 48109 USA. [Seo, Philip] Johns Hopkins Univ, Baltimore, MD USA. [Specks, Ulrich; Ytterberg, Steven R.] Mayo Clin, Rochester, MN USA. [Spiera, Robert] Hosp Special Surg, New York, NY 10021 USA. [St. Clair, E. William] Duke Univ, Durham, NC USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Merkel, PA (reprint author), Boston Univ, Sch Med, Rheumatol Sect, E533,72 E Concord St, Boston, MA 02118 USA. EM pmerkel@bu.edu OI LaValley, Michael/0000-0002-8488-5170 FU Vasculitis Clinical Research Consortium; National Institute of Arthritis and Musculoskeletal and Skin Diseases [U54-AR-057319, RC1-AR-058303, U01-AR-51874, N01-AR-92240, K23-AR-052820, K24-AR-02126, K24-AR-049185, K24-AR-2224]; National Center for Research Resources [U54-RR-019497, RR-025771]; Office of Rare Diseases Research; Mayo Clinic [RR-024150-01]; Johns Hopkins University [RR-025005]; FDA Office of Orphan Products [FD-R-001652]; General Clinical Research Center [M01-RRO-00533]; University of Michigan [M01-RRO-0042]; Duke University [MO1-RR-30]; Johns Hopkins University School of Medicine, National Center for Research Resources/NIH [M01-RRO-2719]; Canadian Institutes of Health Research; Arthritis Foundation; Genentech; Roche FX Sponsored by the Vasculitis Clinical Research Consortium, which has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grants U54-AR-057319, RC1-AR-058303, and U01-AR-51874), the National Center for Research Resources (grant U54-RR-019497), and the Office of Rare Diseases Research. The Vasculitis Clinical Research Consortium is also supported by a Clinical and Translational Science Award from the National Center for Research Resources to Boston University (RR-025771), the Mayo Clinic (RR-024150-01), and Johns Hopkins University (RR-025005). The Wegener's Granulomatosis Etanercept Trial was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant N01-AR-92240), the FDA Office of Orphan Products (grant FD-R-001652), and General Clinical Research Center Grants to Boston University (M01-RRO-00533), University of Michigan (M01-RRO-0042), Duke University (MO1-RR-30), and Johns Hopkins University School of Medicine (M01-RRO-2719) from the National Center for Research Resources/NIH. Dr. Walsh's work was supported by a Canadian Institutes of Health Research Randomized Controlled Trial Mentoring Award. Dr. Monach's work was supported by an Arthritis Foundation Investigator Award. Dr. Seo's work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant K23-AR-052820). Drs. St. Clair, Stone, and Merkel's work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grants K24-AR-02126, K24-AR-049185, and K24-AR-2224).; Dr. Spiera has received consultancy fees, speaking fees, and/or honoraria (less than $10,000 each) from Genentech and Roche. NR 30 TC 19 Z9 19 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD FEB PY 2012 VL 64 IS 2 BP 273 EP 279 DI 10.1002/acr.20649 PG 7 WC Rheumatology SC Rheumatology GA 881EX UT WOS:000299465200016 PM 21954229 ER PT J AU Aplenc, R Pasquini, MC Zhang, MJ Zhu, X McCarthy, PL Ho, VT Cooke, KR Sung, L Bunin, NJ AF Aplenc, R. Pasquini, M. C. Zhang, M. -J Zhu, X. McCarthy, P. L. Ho, V. T. Cooke, K. R. Sung, L. Bunin, N. J. TI EFFECTS OF BODY MASS INDEX (BMI) IN CHILDREN UNDERGOING ALLOGENEIC BONE MARROW TRANSPLANT (BMT) FOR HEMATOLOGIC MALIGNANCIES SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Aplenc, R.; Bunin, N. J.] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Pasquini, M. C.; Zhang, M. -J; Zhu, X.] Med Coll Wisconsin, CIBMTR, Milwaukee, WI USA. [McCarthy, P. L.] Roswell Pk Canc Inst, Buffalo, NY USA. [Ho, V. T.] Dana Farber Canc Inst, Boston, MA USA. [Sung, L.] Hosp Sick Children, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 74 BP S230 EP S230 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600075 ER PT J AU Boyiadzis, M Klein, JP Arora, M Weisdorf, DJ Hassebroek, A Lee, SJ Flowers, ME Cutler, CS Urbano-Ispizua, A Antin, JH Bolwell, BJ Cahn, JY Cairo, MS Gale, RP Herzig, RH Isola, LM Jacobsohn, DA Jagasia, MH Klumpp, TR Petersdorf, EW Wingard, JR Horowitz, MM Pavletic, SZ AF Boyiadzis, M. Klein, J. P. Arora, M. Weisdorf, D. J. Hassebroek, A. Lee, S. J. Flowers, M. E. Cutler, C. S. Urbano-Ispizua, A. Antin, J. H. Bolwell, B. J. Cahn, J-Y Cairo, M. S. Gale, R. P. Herzig, R. H. Isola, L. M. Jacobsohn, D. A. Jagasia, M. H. Klumpp, T. R. Petersdorf, E. W. Wingard, J. R. Horowitz, M. M. Pavletic, S. Z. TI IMPACT OF CHRONIC GVHD ON LATE RELAPSE, TREATMENT RELATED MORTALITY AND SURVIVAL AFTER ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FOR HEMATOLOGICAL MALIGNANCIES SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Boyiadzis, M.] UPMC Canc Ctr, Pittsburgh, PA USA. [Klein, J. P.; Horowitz, M. M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Arora, M.; Weisdorf, D. J.] Univ Minnesota Med Ctr, Minneapolis, MN USA. [Hassebroek, A.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Lee, S. J.; Flowers, M. E.; Petersdorf, E. W.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cutler, C. S.; Antin, J. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Urbano-Ispizua, A.] Hosp Clin Barcelona, Barcelona, Spain. [Bolwell, B. J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Cahn, J-Y] CHU Grenoble, Hosp A Michallon, F-38043 Grenoble, France. [Cairo, M. S.] Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY USA. [Gale, R. P.] Celgene Corp, Los Angeles, CA USA. [Herzig, R. H.] James Brown Canc Ctr, Louisville, KY USA. [Isola, L. M.] Mt Sinai Sch Med, New York, NY USA. [Jacobsohn, D. A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Jagasia, M. H.] Vanderbilt Univ Sch Med, Nashville, TN USA. [Klumpp, T. R.] Temple Univ Bone Marrow Transplant Program, Philadelphia, PA USA. [Wingard, J. R.] Univ Florida, Gainesville, FL USA. [Wingard, J. R.] Shands HealthCare, Gainesville, FL USA. [Pavletic, S. Z.] NCI, Bethesda, MD 20892 USA. RI Cahn, Jean-Yves/M-6493-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 19 BP S209 EP S210 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600020 ER PT J AU Buchbinder, D Nugent, D Brazauskas, R Wang, Z Aljurf, M Cairo, MS Chow, R Duncan, C Eldjerou, LK Gupta, V Hale, GA Halter, J Hayes-Lattin, BM Hsu, JW Jacobsohn, DA Kamble, RT Kasow, KA Lazarus, HM Mehta, P Myers, KC Parsons, SK Passweg, JR Pidala, J Reddy, V Sales-Bonfim, CM Savani, BN Seber, A Sorror, ML Steinberg, A Wood, WA Wall, DA Winiarski, JH Yu, LC Majhail, NS AF Buchbinder, D. Nugent, D. Brazauskas, R. Wang, Z. Aljurf, M. Cairo, M. S. Chow, R. Duncan, C. Eldjerou, L. K. Gupta, V Hale, G. A. Halter, J. Hayes-Lattin, B. M. Hsu, J. W. Jacobsohn, D. A. Kamble, R. T. Kasow, K. A. Lazarus, H. M. Mehta, P. Myers, K. C. Parsons, S. K. Passweg, J. R. Pidala, J. Reddy, V Sales-Bonfim, C. M. Savani, B. N. Seber, A. Sorror, M. L. Steinberg, A. Wood, W. A. Wall, D. A. Winiarski, J. H. Yu, L. C. Majhail, N. S. TI LATE EFFECTS IN HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS WITH ACQUIRED SEVERE APLASTIC ANEMIA: A REPORT FROM THE LATE EFFECTS WORKING COMMITTEE OF THE CENTER FOR INTERNATIONAL BLOOD AND MARROW TRANSPLANT RESEARCH (CIBMTR) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Buchbinder, D.; Nugent, D.] UC Irvine, CHOC Childrens Hosp, Orange, CA USA. [Brazauskas, R.; Wang, Z.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Aljurf, M.] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, TX, Saudi Arabia. [Cairo, M. S.] New York Med Coll, Valhalla, NY 10595 USA. [Chow, R.] Stemcyte, Covina, CA USA. [Duncan, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Eldjerou, L. K.; Hsu, J. W.] Univ Florida, Gainesville, FL USA. [Gupta, V] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Hale, G. A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Halter, J.; Passweg, J. R.] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Hayes-Lattin, B. M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Jacobsohn, D. A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Kamble, R. T.] Baylor Coll Med, Ctr Cell Therapy, Houston, TX 77030 USA. [Kasow, K. A.] Univ N Carolina Hosp, Chapel Hill, NC USA. [Lazarus, H. M.] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [Mehta, P.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Myers, K. C.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Parsons, S. K.] Tufts Med Ctr, Boston, MA USA. [Pidala, J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Reddy, V] Florida Ctr Cellular Therapy, Orlando, FL USA. [Sales-Bonfim, C. M.] Univ Fed Parana, BR-80060000 Curitiba, Parana, Brazil. [Savani, B. N.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Seber, A.] Inst Oncol Pediat, Sao Paulo, Brazil. [Sorror, M. L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Steinberg, A.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Wood, W. A.] Univ N Carolina, Chapel Hill, NC USA. [Wall, D. A.] Univ Manitoba, Winnipeg, MB, Canada. [Winiarski, J. H.] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden. [Yu, L. C.] Childrens Hosp LSU Helath Sci Ctr, New Orleans, LA USA. [Majhail, N. S.] Natl Marrow Donor Program, Minneapolis, MN USA. RI Halter, Joerg/C-9487-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 63 BP S226 EP S226 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600064 ER PT J AU Burkhardt, UE Desmarais, C Robins, HS Wu, D Wong, J Neuberg, D Alyea, EP Soiffer, RJ Wu, CJ AF Burkhardt, U. E. Desmarais, C. Robins, H. S. Wu, D. Wong, J. Neuberg, D. Alyea, E. P. Soiffer, R. J. Wu, C. J. TI EARLY POST-TRANSPLANT WHOLE TUMOR CELL-BASED VACCINATION ALTERS THE KINETICS OF T CELL RECONSTITUTION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Burkhardt, U. E.; Wu, D.; Wong, J.; Neuberg, D.; Alyea, E. P.; Soiffer, R. J.; Wu, C. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Desmarais, C.; Robins, H. S.] Adapt TCR Technol, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 58 BP S224 EP S224 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600059 ER PT J AU Carpenter, PA Chai, X Kurland, BF Palmer, JM Inamoto, Y Martin, PJ Johnston, L Arora, M Cutler, C Arai, S Flowers, ME Jacobsohn, D Pavletic, S Lee, SJ AF Carpenter, P. A. Chai, X. Kurland, B. F. Palmer, J. M. Inamoto, Y. Martin, P. J. Johnston, L. Arora, M. Cutler, C. Arai, S. Flowers, M. E. Jacobsohn, D. Pavletic, S. Lee, S. J. TI RECOMMENDED MEASURES FOR JOINT CHRONIC GVHD: RESULTS FROM THE CHRONIC GVHD CONSORTIUM SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Carpenter, P. A.; Chai, X.; Kurland, B. F.; Inamoto, Y.; Martin, P. J.; Flowers, M. E.; Lee, S. J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Palmer, J. M.] Med Coll Wisconsin, Milwaulkee, WI USA. [Johnston, L.; Arai, S.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Cutler, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jacobsohn, D.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pavletic, S.] NCI, Bethesda, MD 20892 USA. [Arora, M.] Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 414 BP S357 EP S357 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600413 ER PT J AU Castellarin, P Stevenson, K Treister, N AF Castellarin, P. Stevenson, K. Treister, N. TI SEVERE DENTAL CARIES IN PATIENTS WITH ORAL CHRONIC GRAFT-VERSUS-HOST DISEASE SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Treister, N.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Stevenson, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Castellarin, P.] Univ Trieste, Trieste, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 448 BP S369 EP S369 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600447 ER PT J AU Chen, YB McDonough, S Chen, H Kennedy, J Ballen, KK Dey, BR McAfee, SL Spitzer, TR Jagasia, M Ritz, J AF Chen, Y. -B McDonough, S. Chen, H. Kennedy, J. Ballen, K. K. Dey, B. R. McAfee, S. L. Spitzer, T. R. Jagasia, M. Ritz, J. TI EXPRESSION OF alpha 4 beta 7 INTEGRIN ON MEMORY CD8+T-CELLS IS INCREASED IN PATIENTS AT PRESENTATION OF ACUTE INTESTINAL GRAFT-VS-HOST DISEASE SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Chen, Y. -B; Kennedy, J.; Ballen, K. K.; Dey, B. R.; McAfee, S. L.; Spitzer, T. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McDonough, S.; Ritz, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, H.; Jagasia, M.] Vanderbilt Univ, Nashville, TN USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 49 BP S221 EP S221 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600050 ER PT J AU Chen, YB McDonough, S Chen, H Kennedy, J Alyea, EP Armand, P Ballen, KK Cutler, C Dey, BR Ho, VT Koreth, J McAfee, SL Spitzer, TR Antin, JH Soiffer, RJ Jagasia, M Ritz, J AF Chen, Y-B McDonough, S. Chen, H. Kennedy, J. Alyea, E. P. Armand, P. Ballen, K. K. Cutler, C. Dey, B. R. Ho, V. T. Koreth, J. McAfee, S. L. Spitzer, T. R. Antin, J. H. Soiffer, R. J. Jagasia, M. Ritz, J. TI EXPRESSION OF alpha 4 beta 7 INTEGRIN ON PERIPHERAL BLOOD MEMORY CD4+T-CELLS AFTER ALLOGENEIC HCT CORRELATES WITH NON-RELAPSE MORTALITY AND OVERALL SURVIVAL SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Chen, Y-B; Kennedy, J.; Ballen, K. K.; Dey, B. R.; McAfee, S. L.; Spitzer, T. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McDonough, S.; Alyea, E. P.; Armand, P.; Cutler, C.; Ho, V. T.; Koreth, J.; Antin, J. H.; Soiffer, R. J.; Ritz, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, H.; Jagasia, M.] Vanderbilt Univ, Nashville, TN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 350 BP S334 EP S334 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600349 ER PT J AU Chen, YB McDonough, S Chen, H Kennedy, J Coughlin, E Jagasia, M Cutler, C Ritz, J AF Chen, Y-B McDonough, S. Chen, H. Kennedy, J. Coughlin, E. Jagasia, M. Cutler, C. Ritz, J. TI EXPRESSION OF CD30 IS INCREASED ON CD8+T-CELLS IN PATIENTS WITH ACUTE GRAFT-VS-HOST DISEASE SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Chen, Y-B; Kennedy, J.; Coughlin, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McDonough, S.; Cutler, C.; Ritz, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, H.; Jagasia, M.] Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 22 BP S210 EP S210 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600023 ER PT J AU Chirnomas, D Lehmann, L London, W Duncan, C Powell, A Barry, E AF Chirnomas, D. Lehmann, L. London, W. Duncan, C. Powell, A. Barry, E. TI PROSPECTIVE STUDY USING R2 MRI DEMONSTRATES HIGH IRON BURDEN IN ALLOGENEIC PEDIATRIC STEM CELL TRANSPLANT RECIPIENTS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Chirnomas, D.] Yale Sch Med, New Haven, CT USA. [Lehmann, L.; London, W.; Duncan, C.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Barry, E.] Sanofi Oncol, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 272 BP S306 EP S306 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600273 ER PT J AU Freytes, CO Toro, JJ Yeh, RF Stadtmauer, EA Ratanatharathorn, V Akpek, G Sahovic, E Tricot, GJ Shaughnessy, PJ White, DJ Rodriguez, TE Solomon, SR Yu, L Patil, S Sun, Y Armstrong, E Elekes, A Kato, K Reece, DE AF Freytes, C. O. Toro, J. J. Yeh, R. F. Stadtmauer, E. A. Ratanatharathorn, V Akpek, G. Sahovic, E. Tricot, G. J. Shaughnessy, P. J. White, D. J. Rodriguez, T. E. Solomon, S. R. Yu, L. Patil, S. Sun, Y. Armstrong, E. Elekes, A. Kato, K. Reece, D. E. TI PHARMACOKINETICS AND SAFETY OF ONCE-DAILY INTRAVENOUS BUSULFAN WITH BORTEZOMIB IN PATIENTS WITH RELAPSED MULTIPLE MYELOMA UNDERGOING A SECOND AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Freytes, C. O.; Toro, J. J.] Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, C. O.; Toro, J. J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Yeh, R. F.; Yu, L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Stadtmauer, E. A.] Univ Penn, Philadelphia, PA 19104 USA. [Ratanatharathorn, V] Karmanos Canc Inst, Detroit, MI USA. [Akpek, G.] Univ Maryland, Baltimore, MD 21201 USA. [Sahovic, E.] Western Penn Hosp, Pittsburgh, PA 15224 USA. [Tricot, G. J.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Shaughnessy, P. J.] Texas Transplant Inst, San Antonio, TX USA. [White, D. J.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Rodriguez, T. E.] Loyola Univ Chicago Med Ctr, Maywood, IL USA. [Solomon, S. R.] Northside Hosp, Atlanta, GA USA. [Patil, S.; Sun, Y.; Armstrong, E.; Elekes, A.; Kato, K.] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ USA. [Reece, D. E.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 132 BP S253 EP S253 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600133 ER PT J AU Glotzbecker, B Mills, H Rosenblatt, J Joyce, R Levine, J Tzachanis, D Stevenson, M Attar, E Ballen, K Chen, YB Boussiotis, V Zwicker, J Luptakova, K Arnason, J Bonhoff, J Delaney, C Conway, K Giallombardo, N Mortellite, J Fitzgerald, D O'Brien, S McMahon, C Vasir, B Stroopinsky, D Spitzer, T Avigan, D AF Glotzbecker, B. Mills, H. Rosenblatt, J. Joyce, R. Levine, J. Tzachanis, D. Stevenson, M. Attar, E. Ballen, K. Chen, Y. -B Boussiotis, V Zwicker, J. Luptakova, K. Arnason, J. Bonhoff, J. Delaney, C. Conway, K. Giallombardo, N. Mortellite, J. Fitzgerald, D. O'Brien, S. McMahon, C. Vasir, B. Stroopinsky, D. Spitzer, T. Avigan, D. TI ADDITION OF CLOFARABINE TO TLI/ATG CONDITIONING: IMPACT ON IMMUNE RECONSTITUTION AND CLINICAL OUTCOMES SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Glotzbecker, B.; Mills, H.; Rosenblatt, J.; Joyce, R.; Levine, J.; Tzachanis, D.; Stevenson, M.; Boussiotis, V; Zwicker, J.; Luptakova, K.; Arnason, J.; Bonhoff, J.; Delaney, C.; Conway, K.; Giallombardo, N.; Mortellite, J.; Fitzgerald, D.; O'Brien, S.; McMahon, C.; Stroopinsky, D.; Avigan, D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Glotzbecker, B.; Vasir, B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Attar, E.; Ballen, K.; Chen, Y. -B; Spitzer, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 27 BP S213 EP S213 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600028 ER PT J AU Glotzbecker, BF Ho, VT Aldridge, J Kim, HT Horowitz, G Ritz, J Soiffer, RJ Avigan, D Rosenblatt, J AF Glotzbecker, B. E. Ho, V. T. Aldridge, J. Kim, H. T. Horowitz, G. Ritz, J. Soiffer, R. J. Avigan, D. Rosenblatt, J. TI LOW LEVELS OF 25-HYDROXYVITAMIN D PRIOR TO ALLOGENEIC TRANSPLANTATION CORRELATE WITH THE DEVELOPMENT OF CHRONIC GRAFT-VERSUS-HOST DISEASE SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Glotzbecker, B. E.; Ho, V. T.; Aldridge, J.; Kim, H. T.; Ritz, J.; Soiffer, R. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Horowitz, G.; Avigan, D.; Rosenblatt, J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 51 BP S221 EP S221 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600052 ER PT J AU Khera, N Storer, BE Chapko, MK Lee, SJ AF Khera, N. Storer, B. E. Chapko, M. K. Lee, S. J. TI CLINICAL OUTCOMES AND COSTS OF SECOND ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Khera, N.; Storer, B. E.; Lee, S. J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Chapko, M. K.] VA Puget Sound, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 372 BP S341 EP S342 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600371 ER PT J AU King, BS Crown, D Luckey, CJ Emmert, A AF King, B. S. Crown, D. Luckey, C. J. Emmert, A. TI A NOVEL APHERESIS SCHEDULING APPROACH TO INCREASE FACILITY THROUGHPUT SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [King, B. S.; Crown, D.; Luckey, C. J.; Emmert, A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 487 BP S382 EP S383 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600486 ER PT J AU Kornblit, B Storer, B Storb, RF Hari, P Vucinic, V Maziarz, RT Chauncey, T Pulsipher, MA Bruno, B Petersen, FB Bethge, WA Hubel, K Storek, J Maloney, DG Sandmaier, BM AF Kornblit, B. Storer, B. Storb, R. F. Hari, P. Vucinic, V. Maziarz, R. T. Chauncey, T. Pulsipher, M. A. Bruno, B. Petersen, F. B. Bethge, W. A. Hubel, K. Storek, J. Maloney, D. G. Sandmaier, B. M. TI A RANDOMIZED PHASE III TRIAL INVESTIGATING 2 Gy TBI VS. Flu/2 Gy TBI CONDITIONING FOR HLA-MATCHED RELATED DONOR HEMATOPOIETIC CELL TRANSPLANTATION (HCT): TEMPO OF CD3 AND NK CELL ENGRAFTMENT DETERMINES RELAPSE AND PROGRESSION FREE SURVIVAL IN PATIENTS WITH HEMATOLOGIC SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Kornblit, B.; Storer, B.; Storb, R. F.; Chauncey, T.; Maloney, D. G.; Sandmaier, B. M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kornblit, B.; Storer, B.; Storb, R. F.; Chauncey, T.; Maloney, D. G.; Sandmaier, B. M.] Univ Washington, Seattle, WA 98195 USA. [Hari, P.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Vucinic, V.] Univ Leipzig, Leipzig, Germany. [Maziarz, R. T.] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA. [Chauncey, T.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Pulsipher, M. A.] Univ Utah, Med Ctr, Salt Lake City, UT USA. [Bruno, B.] Univ Turin, Sch Med, Turin, Italy. [Petersen, F. B.] LDS Hosp, Salt Lake City, UT USA. [Bethge, W. A.] Univ Tubingen, Med Ctr, Tubingen, Germany. [Hubel, K.] Univ Cologne, D-50931 Cologne, Germany. [Storek, J.] Univ Calgary, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 31 BP S214 EP S214 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600032 ER PT J AU LeGall, JB Milone, M Waxman, J Shaw, L Harrison, L Duffy, D van de Ven, C Militano, O Geyer, M Morris, E Lowe, LB Cairo, MS AF LeGall, J. B. Milone, M. Waxman, J. Shaw, L. Harrison, L. Duffy, D. van de Ven, C. Militano, O. Geyer, M. Morris, E. Lowe, Baxter L. Cairo, M. S. TI INTRAVENOUS (IV) BUSULFAN (BU) ADMINISTERED TWICE DAILY DURING CONDITIONING PRIOR TO ALLOGENEIC STEM CELL TRANSPLANT (ALLOSCT) IN PEDIATRIC RECIPIENTS HAS SIGNIFICANTLY DIFFERENT HALF-LIFE OF ELIMINATION AND CLEARANCE IN RECIPIENTS > 4 YEARS AND THOSE <= 4 YEARS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [LeGall, J. B.] Columbia Univ, New York, NY USA. [Shaw, L.] Univ Penn, Philadelphia, PA 19104 USA. [Milone, M.; Waxman, J.] Bristol Myers Squibb Co, New York, NY 10154 USA. [Militano, O.; Geyer, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Lowe, Baxter L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Harrison, L.; Duffy, D.; van de Ven, C.; Morris, E.; Cairo, M. S.] New York Med Coll, Valhalla, NY 10595 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 267 BP S304 EP S304 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600268 ER PT J AU Lill, M Lim, S Yeh, RF Waller, E Costa, LJ Shore, T Craig, M Freytes, CO Shea, TC Mineishi, S Rondelli, D Horwitz, ME Braunschweig, I Fay, JW Mason, JR Yu, LH Patil, S Sun, Y Armstrong, E Elekes, A Kato, K Vaughan, WP AF Lill, M. Lim, S. Yeh, R. F. Waller, E. Costa, L. J. Shore, T. Craig, M. Freytes, C. O. Shea, T. C. Mineishi, S. Rondelli, D. Horwitz, M. E. Braunschweig, I. Fay, J. W. Mason, J. R. Yu, L. H. Patil, S. Sun, Y. Armstrong, E. Elekes, A. Kato, K. Vaughan, W. P. TI DOSE PRECISION USING A PRETRANSPLANT TEST PK OF INTRAVENOUS BUSULFAN PRIOR TO BuCyVP-16 PREPARATIVE REGIMEN IN LYMPHOMA SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Lill, M.; Lim, S.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Yeh, R. F.; Yu, L. H.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98104 USA. [Waller, E.] Emory Univ, Atlanta, GA 30322 USA. [Costa, L. J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Shore, T.] Cornell Univ, Weil Med Coll, New York, NY 10021 USA. [Shore, T.] New York Presbyterian Hosp, New York, NY USA. [Craig, M.] W Virginia Univ, Morgantown, WV 26506 USA. [Freytes, C. O.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. [Freytes, C. O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Shea, T. C.] Univ N Carolina, Chapel Hill, NC USA. [Mineishi, S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Rondelli, D.] Univ Illinois, Ctr Canc, Chicago, IL USA. [Horwitz, M. E.] Duke Univ, Med Ctr, Durham, NC USA. [Braunschweig, I.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Fay, J. W.] Baylor Univ, Med Ctr, Dallas, TX USA. [Mason, J. R.] Scripps Clin, La Jolla, CA 92037 USA. [Patil, S.; Sun, Y.; Armstrong, E.; Elekes, A.; Kato, K.] Otruka Pharmaceutical Dev & Commercializat Inc, Princeton, NJ USA. [Vaughan, W. P.] Univ Alabaman, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 114 BP S246 EP S246 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600115 ER PT J AU Liney, D Lee, MA Sun, P London, WB Lehmann, LE AF Liney, D. Lee, M. A. Sun, P. London, W. B. Lehmann, L. E. TI COMPARISON OF SURVIVAL AND INCIDENCE OF GRAFT VERSUS HOST DISEASE IN FULLY MATCHED, SINGLE C MISMATCHED AND OTHER MISMATCHED UNRELATED DONOR HEMATOPOIETIC STEM CELL TRANSPLANTS IN A PEDIATRIC POPULATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Liney, D.; Sun, P.; London, W. B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lee, M. A.; Lehmann, L. E.] Dana Farber Childrens Hosp Canc Care, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 277 BP S307 EP S308 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600278 ER PT J AU Marty, FM Winston, D Rowley, SD Boeckh, M Vance, E Papanicolaou, G Robertson, A Godkin, S Painter, W AF Marty, F. M. Winston, D. Rowley, S. D. Boeckh, M. Vance, E. Papanicolaou, G. Robertson, A. Godkin, S. Painter, W. TI CMX001 FOR PREVENTION AND CONTROL OF CMV INFECTION IN CMV-SEROPOSITIVE ALLOGENEIC STEM-CELL TRANSPLANT RECIPIENTS: A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-ESCALATION TRIAL OF SAFETY, TOLERABILITY AND ANTIVIRAL ACTIVITY SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Marty, F. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Marty, F. M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Winston, D.] Univ Calif Los Angeles, Los Angeles, CA USA. [Rowley, S. D.] Hackensack Univ Med Ctr, Hackensack, NJ USA. [Boeckh, M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Vance, E.] Texas Oncol Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [Papanicolaou, G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Robertson, A.; Godkin, S.; Painter, W.] Chimerix Inc, Durham, NC USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 5 BP S203 EP S204 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600006 ER PT J AU Newell, LF Leeborg, N Dong, ZM Avraham, GP Deans, R Chauncey, TR Maziarz, RT AF Newell, L. F. Leeborg, N. Dong, Z. M. Avraham, Perets G. Deans, R. Chauncey, T. R. Maziarz, R. T. TI MULTIPOTENT ADULT PROGENITOR CELLS (MULTISTEM (R)) ENHANCE BONE MARROW RECOVERY AFTER ABLATIVE ALLOGENEIC STEM CELL TRANSPLANT SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Newell, L. F.; Leeborg, N.; Avraham, Perets G.; Maziarz, R. T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Dong, Z. M.; Chauncey, T. R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Deans, R.] Athersys Inc, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 164 BP S264 EP S264 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600165 ER PT J AU Pidala, J Vogelsang, G Martin, P Chai, X Storer, B Pavletic, S Weisdorf, D Jagasia, M Cutler, C Palmer, J Jacobsohn, D Arai, S Lee, SJ AF Pidala, J. Vogelsang, G. Martin, P. Chai, X. Storer, B. Pavletic, S. Weisdorf, D. Jagasia, M. Cutler, C. Palmer, J. Jacobsohn, D. Arai, S. Lee, S. J. TI OVERLAP SUBTYPE OF CHRONIC GVHD IS ASSOCIATED WITH ADVERSE PROGNOSIS, FUNCTIONAL IMPAIRMENT, AND INFERIOR PATIENT REPORTED OUTCOMES: A CHRONIC GVHD CONSORTIUM STUDY SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Pidala, J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Martin, P.; Chai, X.; Storer, B.; Lee, S. J.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Pavletic, S.] NCI, Bethesda, MD 20892 USA. [Weisdorf, D.] Univ Minnesota, Minneapolis, MN 55455 USA. [Jagasia, M.] Vanderbilt Univ, Nashville, TN 37235 USA. [Cutler, C.] Dana Farber Canc Inst, Boston, MA USA. [Palmer, J.] Med Coll Wisconsin, Milwaukee, WI USA. [Arai, S.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 6 BP S204 EP S204 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600007 ER PT J AU Rosenblatt, J Stroopinsky, D Mills, H Luptakova, K Vasir, B Joyce, RM Levine, JD Tzachanis, D Arnason, J Galinsky, I Stone, R Kufe, D Reiter, Y Avigan, DE AF Rosenblatt, J. Stroopinsky, D. Mills, H. Luptakova, K. Vasir, B. Joyce, R. M. Levine, J. D. Tzachanis, D. Arnason, J. Galinsky, I Stone, R. Kufe, D. Reiter, Y. Avigan, D. E. TI MUCI INHIBITION REVERSES THE POOR IMMUNOGENICITY OF LEUKEMIA STEM CELLS RENDERING THEM SUSCEPTIBLE TO IMMUNOTHERAPY SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Rosenblatt, J.; Stroopinsky, D.; Mills, H.; Luptakova, K.; Joyce, R. M.; Levine, J. D.; Tzachanis, D.; Arnason, J.; Avigan, D. E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Vasir, B.; Galinsky, I; Stone, R.; Kufe, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Reiter, Y.] Technion Israel Inst Technol, Haifa, Israel. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 305 BP S319 EP S319 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600306 ER PT J AU Rosenblatt, J Stone, R Avivi, I Uhl, L Neuberg, D Joyce, RM Tzachanis, D Levine, JD Boussiotis, V Zwicker, J Arnason, J Luptakova, K Steesma, D DeAngelo, D Galinsky, I Vasir, B Somaiya, P Mills, H Yuan, E Bonhoff, J Delaney, C Drummy, N Nicholson, L Stroopinsky, D Held, V Katz, T Rowe, J Kufe, D Avigan, DE AF Rosenblatt, J. Stone, R. Avivi, I Uhl, L. Neuberg, D. Joyce, R. M. Tzachanis, D. Levine, J. D. Boussiotis, V Zwicker, J. Arnason, J. Luptakova, K. Steesma, D. DeAngelo, D. Galinsky, I Vasir, B. Somaiya, P. Mills, H. Yuan, E. Bonhoff, J. Delaney, C. Drummy, N. Nicholson, L. Stroopinsky, D. Held, V Katz, T. Rowe, J. Kufe, D. Avigan, D. E. TI CLINICAL TRIAL EVALUATING DC/AML FUSION CELL VACCINATION ALONE AND IN CONJUNCTION WITH PD-I BLOCKADE IN AML PATIENTS WHO ACHIEVE A CHEMOTHERAPY-INDUCED REMISSION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Rosenblatt, J.; Uhl, L.; Joyce, R. M.; Tzachanis, D.; Levine, J. D.; Boussiotis, V; Zwicker, J.; Arnason, J.; Luptakova, K.; Somaiya, P.; Mills, H.; Yuan, E.; Bonhoff, J.; Delaney, C.; Drummy, N.; Stroopinsky, D.; Avigan, D. E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Stone, R.; Neuberg, D.; Steesma, D.; DeAngelo, D.; Galinsky, I; Vasir, B.; Nicholson, L.; Kufe, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Avivi, I; Held, V; Katz, T.; Rowe, J.] Rambam Med Ctr, Haifa, Israel. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 229 BP S289 EP S289 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600230 ER PT J AU Schlatzer, DM Dazard, JE Tomecheko, SE Yanik, G Ho, V Chance, MR Cooke, KR AF Schlatzer, D. M. Dazard, Eudes J. Tomecheko, S. E. Yanik, G. Ho, V Chance, M. R. Cooke, K. R. TI HUMAN BIOMARKER DISCOVERY AND PREDICTIVE MODELS OF DISEASE PROGRESSION AND RESPONSE TO THERAPY FOR IDIOPATHIC PNEUMONIA SYNDROME SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Schlatzer, D. M.; Dazard, Eudes J.; Tomecheko, S. E.; Chance, M. R.; Cooke, K. R.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Yanik, G.] Univ Michigan, Ann Arbor, MI 48109 USA. [Ho, V] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 295 BP S314 EP S315 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600296 ER PT J AU Shah, NN Bhojwani, D Silverman, LB Whitlock, JA Richards, K Stetler-Stevenson, M Buzoianu, M Ibrahim, R Pastan, I Wayne, AS AF Shah, N. N. Bhojwani, D. Silverman, L. B. Whitlock, J. A. Richards, K. Stetler-Stevenson, M. Buzoianu, M. Ibrahim, R. Pastan, I Wayne, A. S. TI A NOVEL ANTI-CD22 IMMUNOTOXIN, MOXETUMOMAB PASUDOTOX (HA22, CAT-8015): ACTIVITY IN PEDIATRIC PATIENTS WITH RELAPSED ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (SCT) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Shah, N. N.; Richards, K.; Stetler-Stevenson, M.; Pastan, I; Wayne, A. S.] NIH, Bethesda, MD 20892 USA. [Bhojwani, D.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Silverman, L. B.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Whitlock, J. A.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Buzoianu, M.; Ibrahim, R.] MedImmune LLC, Gaithersburg, MD USA. NR 0 TC 2 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 84 BP S234 EP S234 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600085 ER PT J AU Toro, JJ Haile, DJ Lee, S Jewell, PS Freytes, CO AF Toro, J. J. Haile, D. J. Lee, S. Jewell, P. S. Freytes, C. O. TI USE OF THE VETERANS AFFAIRS NUTRITIONAL STATUS CLASSIFICATION SCHEME IN THE EVALUATION OF SURVIVAL AFTER AUTOLOGOUS PERIPHERAL BLOOD STEM CELL TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Toro, J. J.; Haile, D. J.; Lee, S.; Jewell, P. S.; Freytes, C. O.] Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. [Toro, J. J.; Freytes, C. O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 306 BP S319 EP S320 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600307 ER PT J AU Treister, N Lee, S Chai, X Kurland, B Pidala, J Palmer, J Flowers, M Jagasia, M Pavletic, S Cutler, C AF Treister, N. Lee, S. Chai, X. Kurland, B. Pidala, J. Palmer, J. Flowers, M. Jagasia, M. Pavletic, S. Cutler, C. TI MEASUREMENT OF ORAL CHRONIC GRAFT-VERSUS-HOST DISEASE SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meeting CY FEB 01-05, 2012 CL San Diego, CA C1 [Treister, N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lee, S.; Chai, X.; Kurland, B.; Flowers, M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Pidala, J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Palmer, J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Jagasia, M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Pavletic, S.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Cutler, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 430 BP S363 EP S363 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600429 ER PT J AU Fulzele, K Clemens, TL AF Fulzele, Keertik Clemens, Thomas L. TI Novel functions for insulin in bone SO BONE LA English DT Review DE Osteoblasts; Insulin receptor; Osteocalcin; Knockout mice; Glucose homeostasis ID PROTEIN-COUPLED RECEPTOR; MATRIX GLA PROTEIN; GROWTH FACTOR-I; DIABETES-MELLITUS; ENERGY-METABOLISM; TYROSINE KINASE; GLUCOSE-TRANSPORT; CRYSTAL-STRUCTURE; DEFICIENT MICE; BETA-CELL AB The insulin-like growth factors (IGF) evolved in lower animals to enable a wide range of physiologic processes, including smell, food consumption, metabolism, growth, reproduction, and dormancy. These functions were accomplished by the actions of multiple related ligands that activated a common transmembrane receptor protein. In higher organisms, including mammals, the insulin and IGF ligands and their receptors evolved to function in a more circumscribed fashion. The contemporary model assigns IGFs as central regulators of cell proliferation, survival, and organism growth, whereas insulin's action dominates at the level of regulation of fuel accumulation, storage, and energy expenditure. Such a simplistic paradigm, however, obscures the fact that insulin and IGF-1 continue to exert overlapping roles in several physiologic processes. Indeed, recent studies have identified previously, unappreciated skeletal actions of insulin, which suggests that insulin-responsive bone cells participate in the regulation of global energy homeostasis. These findings raise intriguing questions on the nature of the fuel sensing and processing mechanisms in bone and their relative importance to overall energy homeostasis in mammals. Answers to these questions should ultimately improve the ability to diagnose and manage patients with metabolic diseases such as diabetes and osteoporosis. This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism. (C) 2011 Published by Elsevier Inc. C1 [Clemens, Thomas L.] Johns Hopkins Univ, Johns Hopkins Bayview Med Ctr, Editorial Serv, Dept Orthopaed Surg, Baltimore, MD 21224 USA. [Clemens, Thomas L.] Baltimore Vet Adm, Med Ctr, Baltimore, MD USA. [Fulzele, Keertik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. RP Clemens, TL (reprint author), Johns Hopkins Univ, Johns Hopkins Bayview Med Ctr, Editorial Serv, Dept Orthopaed Surg, 4940 Eastern Ave,A665, Baltimore, MD 21224 USA. EM kfulzele@partners.org; tclemen5@jhmi.edu FU Veterans Administration FX The authors thank Elaine P. Henze, BJ, ELS, Medical Editor and Director, Editorial Services, Department of Orthopaedic Surgery, Johns Hopkins Bayview Medical Center, for editorial assistance with the manuscript. This work was supported in part by a Merit Review Grant from the Veterans Administration. Dr. Clemens is a recipient of a Career Scientist Award from the Veterans Administration. NR 56 TC 29 Z9 32 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD FEB PY 2012 VL 50 IS 2 SI SI BP 452 EP 456 DI 10.1016/j.bone.2011.06.018 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 884OV UT WOS:000299718300005 PM 21723973 ER PT J AU Casaburi, R Porszasz, J Hecht, A Tiep, B Albert, RK Anthonisen, NR Bailey, WC Connett, JE Cooper, JA Criner, GJ Curtis, J Dransfield, M Lazarus, SC Make, B Martinez, FJ McEvoy, C Niewoehner, DE Reilly, JJ Scanlon, P Scharf, SM Sciurba, FC Woodruff, P AF Casaburi, Richard Porszasz, Janos Hecht, Ariel Tiep, Brian Albert, Richard K. Anthonisen, Nicholas R. Bailey, William C. Connett, John E. Cooper, J. Allen, Jr. Criner, Gerard J. Curtis, Jeffrey Dransfield, Mark Lazarus, Stephen C. Make, Barry Martinez, Fernando J. McEvoy, Charlene Niewoehner, Dennis E. Reilly, John J. Scanlon, Paul Scharf, Steven M. Sciurba, Frank C. Woodruff, Prescott CA COPD Clinical Res Network TI Influence of Lightweight Ambulatory Oxygen on Oxygen Use and Activity Patterns of COPD Patients Receiving Long-Term Oxygen Therapy SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE adherence; long-term oxygen therapy; activity monitoring; tri-axial accelerometer ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED-TRIAL; STANDARDIZATION; HOME; PRESCRIPTION; POPULATION; SURVIVAL; LUNG AB Lightweight ambulatory oxygen devices are provided on the assumptions that they enhance compliance and increase activity, but data to support these assumptions are lacking. We studied 22 patients with severe chronic obstructive pulmonary disease receiving long-term oxygen therapy (14 men, average age = 66.9 y, FEV1 = 33.6% pred, PaO2 at rest = 51.7 torr) who were using E-cylinders as their portable oxygen. Subjects were recruited at 5 sites and studied over a 2-week baseline period and for 6 months after randomizing them to either continuing to use 22-lb E-cylinders towed on a cart or to carrying 3.6-lb aluminum cylinders. Utilizing novel electronic devices, ambulatory and stationary oxygen use was monitored continuously over the 2 weeks prior to and the 6 months following randomization. Subjects wore tri-axial accelerometers to monitor physical activity during waking hours for 2-3 weeks prior to, and at 3 and 6 months after, randomization. Seventeen subjects completed the study. At baseline, subjects used 17.2 hours of stationary and 2.5 hours of ambulatory oxygen daily. At 6 months, ambulatory oxygen use was 1.4 +/- 1.0 hrs in those randomized to E-cylinders and 1.9 +/- 2.4 hrs in those using lightweight oxygen (P = NS). Activity monitoring revealed low activity levels prior to randomization and no significant increase over time in either group. In this group of severe chronic obstructive pulmonary disease patients, providing lightweight ambulatory oxygen did not increase either oxygen use or activity. Future efforts might focus on strategies to encourage oxygen use and enhance activity in this patient group. This trial is registered at ClinicalTrials.gov (NCT003257540). C1 [Casaburi, Richard; Porszasz, Janos; Hecht, Ariel] Univ Calif Los Angeles, Los Angeles Biomed Res Inst, Med Ctr, Rehabil Clin Trials Ctr, Torrance, CA 90502 USA. [Tiep, Brian] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Albert, Richard K.] Denver Hlth, Dept Med, Denver, CO USA. [Albert, Richard K.] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. [Anthonisen, Nicholas R.] Univ Manitoba, Winnipeg, MB, Canada. [Bailey, William C.; Cooper, J. Allen, Jr.; Dransfield, Mark] Univ Alabama, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA. [Connett, John E.] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Cooper, J. Allen, Jr.; Dransfield, Mark] Birmingham VAMC, Pulm Sect, Birmingham, AL USA. [Criner, Gerard J.] Temple Univ, Div Pulm & Crit Care Med, Philadelphia, PA 19122 USA. [Curtis, Jeffrey; Martinez, Fernando J.] Univ Michigan, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. [Lazarus, Stephen C.; Woodruff, Prescott] Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. [Lazarus, Stephen C.; Woodruff, Prescott] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Make, Barry] Natl Jewish Hlth, Denver, CO USA. [McEvoy, Charlene] HealthPartners Res Fdn, Minneapolis, MN USA. [Niewoehner, Dennis E.] Univ Minnesota, VA Med Ctr, Pulm Sect, Minneapolis, MN USA. [Reilly, John J.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Scanlon, Paul] Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN USA. [Scharf, Steven M.] Univ Maryland, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA. [Sciurba, Frank C.] Univ Pittsburgh, Div Pulm & Crit Care Med, Pittsburgh, PA USA. RP Casaburi, R (reprint author), Univ Calif Los Angeles, Los Angeles Biomed Res Inst, Med Ctr, Rehabil Clin Trials Ctr, Bldg J4,1124 W Carson St, Torrance, CA 90502 USA. EM casaburi@ucla.edu RI Reilly, John/H-8755-2012; OI Curtis, Jeffrey/0000-0001-5191-4847; Porszasz, Janos/0000-0002-5823-0031 FU COPD Clinical Research Network; National Heart, Lung, and Blood Institute [1U10]; National Center for Research Resources; Brigham and Women's Hospital [HL074428, RR02635]; Denver Health Medical Center [L074409, RR00051]; Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center [HL074407, RR00425]; Temple University [HL074408]; University of Alabama at Birmingham [HL074418]; University of California, San Francisco [HL074431]; University of Maryland, Baltimore [HL074441, RR16500]; University of Michigan [HL074422]; University of Pittsburgh [HL074439, RR00056]; Minnesota Veterans Research Institute, Minneapolis [HL074416]; University of Minnesota (Data Coordinating Center) [HL074424]; Data and Safety Monitoring Board FX This study was funded by the COPD Clinical Research Network a w10-site network supported by a Cooperative Agreement (1U10 mechanism) from the National Heart, Lung, and Blood Institute; no funds from commercial sources were utilized. At some sites General Clinical Research Centers (GCRC) were utilized; their M01 grants from the National Center for Research Resources are listed. Members of this Network, with their personnel and grant support are: Brigham and Women's Hospital - J.J. Reilly, Jr. (PI), G. Washko, (Investigator), S. Peterson, C. Mayo (Coordinator), Grant HL074428, GCRC Grant RR02635; Denver Health Medical Center - R. K. Albert (PI), B. Make (Co-PI), C. Welsh (Investigators), M. Gilmartin, C. Verano (Coordinators), Grant HL074409, GCRC Grant RR00051; Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center - R. Casaburi (PI), J. Porszasz (Investigator), R. D. Love (Coordinator), Grant HL074407, GCRC Grant RR00425; Temple University - G. J. Criner (PI); W. Chatila, N. Marchetti, V. Kim, G D'Alonzo, S. Krachman, F. Cordova, K. Brennan, N. Patel, J. Mamary (Investigator), C. Grabianowski, N. Krayger, H. Criner (Coordinators), Grant HL074408; University of Alabama at Birmingham - W. C. Bailey, J. A. D. Cooper (Co-PIs), M. T. Dransfield, L. B Gerald, P. O'Reilly (Investigators), S. Tidwell (Coordinator), Grant HL074418; University of California, San Francisco - S. C. Lazarus (PI), H. A. Boushey, P. G. Woodruff (Investigators), R. Sakurai, C. Nguyen (Coordinators), Grant HL074431; University of Maryland, Baltimore - S. M. Scharf (PI), M. Alattar, P. Amelung, M. Cowan, J. Hanson, J. Hasday, A. Iacono, C. Shanholtz, N. Todd, A. Verceles (Investigators), W. Bell-Farrell, T. Fitzgerald, P. Wood (Coordinators), Grant HL074441, GCRC Grant RR16500; University of Michigan, Ann Arbor - F. J. Martinez (PI), J. Curtis, M. K. Han, P. Christensen (Investigators), K. Baptist, C. Flaherty, C. Getty, C. Jett, L. McCloskey, D. Thompson, D. White (Coordinators), Grant HL074422; University of Pittsburgh - F. Sciurba, (PI), R. Folger, D. Filippino (Coordinators), Grant HL074439, GCRC Grant RR00056; Minnesota Veterans Research Institute, Minneapolis - D. E. Niewoehner (PI), C. McEvoy, P. D. Scanlon, K. R. Rice (Co-PIs), C. B. Bourassa, P. Neuenfeldt (Coordinators), Grant HL074416. University of Minnesota (Data Coordinating Center) - J. E. Connett (PI), N. R. Anthonisen (Steering Committee Chair), C. Wendt (Co-PI), W. Patrek, H. Voelker, M. Skeans (Coordinators), Grant HL074424. Data and Safety Monitoring Board - B. B. Bender, S. F. Kelsey, J. R. Landis, B. Phillips, G. M. Turino, R. Veatch, A. Waldo, A. Wanner. Protocol Review Committee H. W. Kelly, J. Maurer, A. J. McSweeny, R. M. Senior, E. A. Thom, P. D. Wagner, R. L. ZuWallack. NHLBI - G. Weinmann (Deputy Director, Division of Lung Diseases), T. Croxton (Director, Airway Biology & Disease Program), A. Punturieri, (Program Officer), M. P. Stylianou (Bio-statistician). NR 27 TC 19 Z9 19 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1541-2555 J9 COPD JI COPD-J. Chronic Obstr. Pulm. Dis. PD FEB PY 2012 VL 9 IS 1 BP 3 EP 11 DI 10.3109/15412555.2012.630048 PG 9 WC Respiratory System SC Respiratory System GA 884XY UT WOS:000299743400002 PM 22292592 ER PT J AU Nayak, L Lee, EQ Wen, PY AF Nayak, Lakshmi Lee, Eudocia Quant Wen, Patrick Y. TI Epidemiology of Brain Metastases SO CURRENT ONCOLOGY REPORTS LA English DT Article DE Brain metastases; Intracranial; Incidence; Epidemiology; Non-small cell lung cancer; Breast cancer; Melanoma ID CENTRAL-NERVOUS-SYSTEM; CELL LUNG-CANCER; PROPHYLACTIC CRANIAL IRRADIATION; HER2-POSITIVE BREAST-CANCER; CEREBRAL METASTASES; MALIGNANT-MELANOMA; PROGNOSTIC-FACTORS; SOLID TUMORS; ADJUVANT CHEMOTHERAPY; SURGICAL-TREATMENT AB Brain metastases are one of the most common neurologic complications of cancer. The incidence is 9%-17% based on various studies, although the exact incidence is thought to be higher. The incidence is increasing with the availability of improved imaging techniques which aid early diagnosis, and effective systemic treatment regimens which prolong life, thus allowing cancer to disseminate to the brain. Lung cancer, breast cancer, and melanoma are the most frequent to develop brain metastases, and account for 67%-80% of all cancers. Most patients with brain metastases have synchronous extracerebral metastases. Some patients present with no known primary cancer diagnosis. In children, brain metastases are rare; germ cell tumors, sarcomas, and neuroblastoma are the common offenders. C1 [Nayak, Lakshmi; Lee, Eudocia Quant; Wen, Patrick Y.] Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Dept Neurol,Div Neurooncol, Boston, MA 02215 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Dept Neurol,Div Neurooncol, 450 Brookline Ave,SW-430D, Boston, MA 02215 USA. EM Patrick_Wen@dfci.harvard.edu NR 70 TC 97 Z9 100 U1 2 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD FEB PY 2012 VL 14 IS 1 BP 48 EP 54 DI 10.1007/s11912-011-0203-y PG 7 WC Oncology SC Oncology GA 881VV UT WOS:000299519900007 PM 22012633 ER PT J AU Muller-Barna, P Schwamm, LH Haberl, RL AF Mueller-Barna, Peter Schwamm, Lee H. Haberl, Roman L. TI Telestroke increases use of acute stroke therapy SO CURRENT OPINION IN NEUROLOGY LA English DT Review DE acute stroke care; stroke unit; telemedicine; telestroke; thrombolysis ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; TELEMEDIC PILOT PROJECT; REMOTE EVALUATION; POOLED ANALYSIS; CARE TEMPIS; EMERGENCY; RELIABILITY; SYSTEM; THROMBOLYSIS AB Purpose of review This review provides a comprehensive overview of the management of acute stroke within the framework of telestroke services. Recent findings The remote neurological examination using high quality videoconferencing coupled with remote review of neuroimaging has gained acceptance and proved its reliability in various publications. Telestroke networks confirmed the safety and efficiency of telethrombolysis, with an increase in the rate of thrombolysis in recent years. The analysis of a telestroke network in Europe showed improved outcomes in a cohort of ischemic stroke patients. Summary At the beginning of the millennium, telestroke networks started to develop. Ten years later, there is a collection of about 40 various networks in North America and Europe performing teleconsultations on a regular basis. Telestroke is not a new therapeutic modality, but rather a set of tools to enable more efficient delivery of acute stroke care and to improve the quality of stroke care in neurologically underserved areas. Depending on the level of available regional resources, telestroke networks can support affiliated hospitals by implementing measures that improve the quality of stroke management such as regional campaigns, stroke units and stroke teams, medical education and programs encouraging the usage of guidelines. C1 [Mueller-Barna, Peter; Haberl, Roman L.] Stadt Klinikum Munchen GmbH, Dept Neurol, Klinikum Harlaching, D-81545 Munich, Germany. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Muller-Barna, P (reprint author), Stadt Klinikum Munchen GmbH, Dept Neurol, Klinikum Harlaching, Sanat Pl 2, D-81545 Munich, Germany. EM peter.mueller-barna@klinikum-muenchen.de OI Schwamm, Lee/0000-0003-0592-9145 NR 53 TC 21 Z9 21 U1 1 U2 4 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 FEB PY 2012 VL 25 IS 1 BP 5 EP 10 DI 10.1097/WCO.0b013e32834d5fe4 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 876OX UT WOS:000299118100002 PM 22157105 ER PT J AU Zhang, L Alt, C Li, PL White, RM Zon, LI Wei, XB Lin, CP AF Zhang, Li Alt, Clemens Li, Pulin White, Richard M. Zon, Leonard I. Wei, Xunbin Lin, Charles P. TI An optical platform for cell tracking in adult zebrafish SO CYTOMETRY PART A LA English DT Article DE In vivo flow cytometry (IVFC); in vivo confocal microscopy; circulating cells; adult zebrafish AB Adult zebrafish are being increasingly used as a model in cancer and stem cell research. Here we describe an integrated optical system that combines a laser scanning confocal microscope (LSCM) and an in vivo flow cytometer (IVFC) for simultaneous visualization and cell quantification. The system is set up specifically for non-invasive tracking of both stationary and circulating cells in adult zebrafish (casper) that have been engineered to be optically transparent. Confocal imaging in this instrument serves the dual purpose of visualizing fish tissue microstructure and an imaging-based guide to locate a suitable vessel for quantitative analysis of circulating cells by IVFC. We demonstrate initial testing of this novel instrument by imaging the transparent adult zebrafish casper vasculature and tracking circulating cells in CD41-GFP/Gata1-DsRed transgenic fish whose thrombocytes/erythrocytes express the green and red fluorescent proteins. In vivo measurements allow cells to be tracked under physiological conditions in the same fish over time, without drawing blood samples or sacrificing animals. We also discuss the potential applications of this instrument in biomedical research. (C) 2011 International Society for Advancement of Cytometry C1 [Zhang, Li; Alt, Clemens; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Zhang, Li] Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China. [Zhang, Li; Wei, Xunbin] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China. [Li, Pulin; White, Richard M.; Zon, Leonard I.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Harvard Stem Cell Inst,Childrens Hosp, Boston, MA 02115 USA. [Wei, Xunbin] Shanghai Jiao Tong Univ, Med X Res Inst, Shanghai 200240, Peoples R China. [Wei, Xunbin] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200240, Peoples R China. RP Lin, CP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Adv Microscopy Program,Wellman Ctr Photomed, BAR 804,50 Blossom St, Boston, MA 02114 USA. EM xunbinwei@gmail.com; lin@helix.mgh.harvard.edu RI 李, 涵/B-4995-2012 FU China Scholarship Council (CSC) [2008610061]; NIH [HL97794] FX Grant sponsor: China Scholarship Council (CSC); Grant number: 2008610061; Grant sponsor: NIH; Grant number: HL97794. NR 12 TC 15 Z9 15 U1 1 U2 24 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD FEB PY 2012 VL 81A IS 2 BP 176 EP 182 DI 10.1002/cyto.a.21167 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 880AQ UT WOS:000299376900013 PM 22162445 ER PT J AU McNeely, MJ Shofer, JB Leonetti, DL Fujimoto, WY Boyko, EJ AF McNeely, Marguerite J. Shofer, Jane B. Leonetti, Donna L. Fujimoto, Wilfred Y. Boyko, Edward J. TI Associations Among Visceral Fat, All-Cause Mortality, and Obesity-Related Mortality in Japanese Americans SO DIABETES CARE LA English DT Article ID DIABETES-MELLITUS; MEN; DIAGNOSIS; CHOICE AB OBJECTIVE-The study objective was to examine the associations among visceral fat (VF), all-cause mortality, and obesity-related mortality. RESEARCH DESIGN AND METHODS-A total of 733 Japanese Americans were followed for 16.9 years. Hazard ratios (HRs) per interquartile range increase in VF were calculated using time-dependent Cox proportional hazard models censored at age 82 years, with age as the time axis adjusted for sex and smoking. RESULTS-Higher VF was associated with all-cause mortality (HR 1.39 [95% CI 1.11-1.75] 107 deaths) and obesity-related mortality (1.39 [1.04-1.85], 68 deaths from cardiovascular disease, diabetes, or obesity-related cancer). After further adjustment for waist circumference, VF remained significantly associated with all-cause mortality (1.41 [1.04-1.92]) but not with obesity-related mortality. The associations between mortality and VF were not independent of BMI. CONCLUSIONS-VF was associated with all-cause mortality and obesity-related mortality in Japanese Americans. VF did not significantly improve mortality risk assessment beyond that of BMI. C1 [McNeely, Marguerite J.; Fujimoto, Wilfred Y.; Boyko, Edward J.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Shofer, Jane B.] Univ Washington, Ctr Studies Demog & Ecol, Seattle, WA 98195 USA. [Leonetti, Donna L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP McNeely, MJ (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. EM mcneely@u.washington.edu FU National Institutes of Health [DK-77745, DK-31170, HL-49293, DK-02654]; King County Japanese-American Community FX This work was supported by the National Institutes of Health (grants DK-77745, DK-31170, HL-49293, and DK-02654) and by facilities and services provided by the Diabetes and Endocrinology Research Center (DK-17047), Clinical Nutrition Research Unit (DK-35816), and General Clinical Research Center (RR-00037) at the University of Washington. VA Puget Sound provided support for Dr. Boyko's involvement in this research.; The authors thank the King County Japanese-American Community for support and cooperation. NR 13 TC 15 Z9 15 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2012 VL 35 IS 2 BP 296 EP 298 DI 10.2337/dc11-1193 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 886LN UT WOS:000299856000020 PM 22190675 ER PT J AU Delahanty, LM Pan, Q Jablonski, IA Watson, KE McCaffery, JM Shuldiner, A Kahn, SE Knowler, WC Florez, JC Franks, PW AF Delahanty, Linda M. Pan, Qing Jablonski, Icatiileen A. Watson, Karol E. McCaffery, Jeanne M. Shuldiner, Alan Kahn, Steven E. Knowler, William C. Florez, Jose C. Franks, Paul W. CA Diabet Prevention Program Res Grp TI Genetic Predictors of Weight Loss and Weight Regain After Intensive Lifestyle Modification, Metformin Treatment, or Standard Care in the Diabetes Prevention Program SO DIABETES CARE LA English DT Article ID POLYMORPHISMS; INTERVENTION; RECEPTOR AB OBJECTIVE-We tested genetic associations with weight loss and weight regain in the Diabetes Prevention Program, a randomized controlled trial of weight-loss inducing interventions (lifestyle and metformin) versus placebo. RESEARCH DESIGN AND METHODS-Sixteen obesity-predisposing single nucleotide polymorphisms (SNPs) were tested for association with short-term (baseline to 6 months) and long-term (baseline to 2 years) weight loss and weight regain (6 months to study end). RESULTS-Irrespective of treatment, the Ala12 allele at PPARG associated with short- and long-term weight loss (-0.63 and -0.93 kg/allele, P <= 0.005, respectively). Gene-treatment interactions were observed for short-term (LYPLAL1 rs2605100, P-lifestyle*SNP = 0.032; GNPDA2 rs10938397, P-lifestyle*SNP = 0.016; MTCH2 rs10838738, P-lifestyle*SNP = 0.022) and long-term (NEGR1 rs2815752, P-metformin*SNP = 0.028; FTO rs9939609, P-lifestyle*SNP = 0.044) weight loss. Three of 16 SNPs were associated with weight regain (NEGR1 rs2815752, BDNF rs6265, PPARG rs1801282), irrespective of treatment. TMEM18 rs6548238 and KTCD15 rs29941 showed treatment-specific effects (P-lifestyle*SNP < 0.05). CONCLUSIONS-Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention. C1 [Franks, Paul W.] Lund Univ, Skane Univ Hosp, Ctr Diabet, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden. [Delahanty, Linda M.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Delahanty, Linda M.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Pan, Qing; Jablonski, Icatiileen A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Watson, Karol E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [McCaffery, Jeanne M.] Miriam Hosp, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA. [McCaffery, Jeanne M.] Brown Med Sch, Providence, RI USA. [Shuldiner, Alan] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Shuldiner, Alan] Univ Maryland, Sch Med, Program Genet & Genom Med, Baltimore, MD 21201 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Knowler, William C.] NIDDK, Phoenix, AZ USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Franks, PW (reprint author), Lund Univ, Skane Univ Hosp, Ctr Diabet, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden. EM paul.franks@med.lu.se RI de Bakker, Paul/B-8730-2009; Uwaifo, Gabriel/M-2361-2016; OI de Bakker, Paul/0000-0001-7735-7858; Uwaifo, Gabriel/0000-0002-6962-9304; Franks, Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002 FU Novo Nordisk; Swedish Research Council; Swedish Heart-Lung Foundation; Swedish Diabetes Association; Department of Veterans Affairs; Doris Duke Charitable Foundation; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; Indian Health Service; National Center for Research Resources; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association; Henry M. Jackson Foundation; McKesson BioServices Corporation; Matthews Media Group; [R01 DK-072041-02] FX This work was funded by R01 DK-072041-02 to J.C.F., K.A.J., and A.S. (P.W.F. and W.C.K. are coinvestigators). P.W.F. was supported by grants from Novo Nordisk, the Swedish Research Council, the Swedish Heart-Lung Foundation, and the Swedish Diabetes Association. S.E.K. is supported in part by the Department of Veterans Affairs. J.C.F. is supported by a Doris Duke Charitable Foundation Clinical Scientist Development Award. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health funded the clinical centers and the Coordinating Center for the design and conduct of the study and the collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, supported data collection at many of the clinical centers. The Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, Office of Research on Women's Health, the Department of Veterans Affairs, and the American Diabetes Association funded data collection and provided participant support. This research was also supported, in part, by the intramural research program of the NIDDK. The Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center.; LifeScan, Health O Meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck and Co., Nike Sports Marketing, Slim Fast Foods Co., and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. Bristol-Myers Squibb and Parke-Davis provided medication. McKesson BioServices Corporation and Matthews Media Group provided support services under subcontract with the Coordinating Center. No other potential conflicts of interest relevant to this article were reported. NR 12 TC 38 Z9 38 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2012 VL 35 IS 2 BP 363 EP 366 DI 10.2337/dc11-1328 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 886LN UT WOS:000299856000030 PM 22179955 ER PT J AU Kizer, JR Arnold, AM Benkeser, D Ix, JH Djousse, L Zieman, SJ Barzilay, JI Tracy, RP Mantzoros, CS Siscovick, DS Mukamal, KJ AF Kizer, Jorge R. Arnold, Alice M. Benkeser, David Ix, Joachim H. Djousse, Luc Zieman, Susan J. Barzilay, Joshua I. Tracy, Russell P. Mantzoros, Christos S. Siscovick, David S. Mukamal, Kenneth J. TI Total and High-Molecular-Weight Adiponectin and Risk of Incident Diabetes in Older People SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; BETA-CELL FUNCTION; CARDIOVASCULAR HEALTH; INSULIN-RESISTANCE; WOMEN; MEN; POPULATION; ADIPOSITY; MELLITUS; GLUCOSE AB OBJECTIVE-To delineate the associations of total adiponectin, high-molecular-weight (HMW) adiponectin, and the HMW-to-total adiponectin ratio with diabetes in older adults. RESEARCH DESIGN AND METHODS-Total and HMW adiponectin were measured in a population-based study of older adults. The relations of total adiponectin, HMW adiponectin, and their ratio with incident diabetes (n = 309) were assessed in 3,802 individuals. RESULTS-Total and HMW adiponectin were highly correlated (r = 0.94). Analysis using cubic splines revealed that the associations between total and HMW adiponectin and new-onset diabetes were not linear. Specifically, after adjustment for confounders, there were similar inverse relationships for total (hazard ratio per SD 0.49 [95% CI 0.39-0.63]) and HMW adiponectin (0.42 [0.32-0.56]) with diabetes up to values of 20 and 10 mg/L, respectively, above which the associations plateaued. These associations persisted after adjustment for potential mediators (blood pressure, lipids, C-reactive protein, and homeostasis model assessment of insulin resistance [HOMA-IR]). There was, however, evidence of interaction by HOMA-IR in the lower range of adiponectin, with stronger inverse associations among insulin-sensitive than insulin-resistant participants. HMW-to-total adiponectin ratio showed a linear adjusted association with outcome, but this was abolished by inclusion of mediating variables. CONCLUSIONS-In this older cohort, increasing concentrations of total and HMW adiponectin were associated with comparably lower risks of diabetes, but these associations leveled off with further increases above concentrations of 20 and 10 mg/L, respectively. The more pronounced risk decreases at the lower range among participants without insulin resistance support a role for adiponectin that is independent of baseline hyperinsulinemia, but this will require further investigation. C1 [Kizer, Jorge R.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Kizer, Jorge R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Arnold, Alice M.; Benkeser, David] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Djousse, Luc; Mantzoros, Christos S.; Mukamal, Kenneth J.] Harvard Univ, Sch Med, Boston, MA USA. [Zieman, Susan J.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Barzilay, Joshua I.] Emory Univ, Sch Med, Div Endocrinol, Atlanta, GA USA. [Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, VT USA. [Tracy, Russell P.] Univ Vermont, Dept Biochem, Colchester, VT USA. [Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Kizer, JR (reprint author), Weill Cornell Med Coll, Dept Med, New York, NY USA. EM jok2007@med.cornell.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute (NHLBI) [R01-HL-094555, N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, HL-080295]; National Institute of Neurological Disorders and Stroke; National Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058] FX This work was supported by R01-HL-094555 from the National Heart, Lung, and Blood Institute (NHLBI). The CHS was supported by NHLBI contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, and NHLBI Grant HL-080295, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging. See also http://www.chs-nhlbi.org/pi.htm. NR 30 TC 22 Z9 25 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2012 VL 35 IS 2 BP 415 EP 423 DI 10.2337/dc11-1519 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 886LN UT WOS:000299856000038 PM 22148099 ER PT J AU Foster, RG Golden-Mason, L Rutebemberwa, A Rosen, HR AF Foster, Richard G. Golden-Mason, Lucy Rutebemberwa, Alleluiah Rosen, Hugo R. TI Interleukin (IL)-17/IL-22-Producing T cells Enriched Within the Liver of Patients with Chronic Hepatitis C Viral (HCV) Infection SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE HCV; Liver; Th17; IL22; Fibrosis ID INNATE IMMUNITY; TH17 CELLS; EXPRESSION; DISEASE AB Effector CD4+ helper T cells have historically been classified into T helper 1 (Th1) and Th2 based on the production of signature cytokines. The recently identified interleukin (IL)-17 cytokine family plays important roles in host immunity against intracellular pathogens and in chronic inflammatory conditions; data have implicated IL-17 in autoimmune and viral liver disease. This study used three patient groups with HCV infection: acute HCV who either cleared spontaneously or became chronically infected (n = 12), endstage liver disease from whom both peripheral and intrahepatic lymphocytes were studied directly ex vivo (n = 11), and 134 patients with different stages of HCV-related fibrosis from whom serum was collected concurrently with liver biopsy. Normal healthy subjects (n = 41) served as controls. Acute HCV was not associated with expansion of either CD4+ or CD8+ T cells producing IL-17 (Th17, Tc17) or IL-22, and frequencies did not differ in the blood of patients who cleared versus became persistently infected. The hepatic compartment of chronic HCV patients demonstrated statistically more CD4+ and CD8+ that produced IL-17, IL-22 or both as compared to peripheral blood. These T cells displayed a distinct phenotypic profile, high expression of the homing receptor CD161 and low levels of inhibitory receptors, mucin-domain-containing-molecule-3 (Tim-3) and programmed-death 1. Using a sensitive ELISA, we found no significant differences in serum levels of IL-17 according to HCV-related fibrosis. In chronic HCV, T cells producing IL-17/IL-22 may home to the liver; however, circulating levels of IL-17 do not correlate with fibrosis. C1 [Foster, Richard G.; Golden-Mason, Lucy; Rutebemberwa, Alleluiah; Rosen, Hugo R.] Univ Colorado Denver, Dept Med, Hepatitis Ctr C, Div Gastroenterol & Hepatol, Aurora, CO 80045 USA. [Foster, Richard G.; Golden-Mason, Lucy; Rutebemberwa, Alleluiah; Rosen, Hugo R.] Natl Jewish Hosp, Aurora, CO 80045 USA. [Golden-Mason, Lucy; Rosen, Hugo R.] Univ Colorado, Integrated Program Immunol, Denver, CO 80202 USA. [Golden-Mason, Lucy; Rosen, Hugo R.] Natl Jewish Hosp, Denver, CO USA. [Golden-Mason, Lucy; Rosen, Hugo R.] Eastern Colorado VA, Denver, CO USA. [Rosen, Hugo R.] Denver VA Med Ctr, Denver, CO USA. RP Rosen, HR (reprint author), Univ Colorado Denver, Dept Med, Hepatitis Ctr C, Div Gastroenterol & Hepatol, B-158,Acad Off Bldg 1,12631 E 17th Ave,Rm 7614,PO, Aurora, CO 80045 USA. EM hugo.rosen@ucdenver.edu FU HCV center [U19 A 1066328-01]; VA Merit Review grant FX This research is supported by a VA Merit Review grant and U19 A 1066328-01 (HCV center grant) to H.R.R. NR 19 TC 24 Z9 26 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 2012 VL 57 IS 2 BP 381 EP 389 DI 10.1007/s10620-011-1997-z PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 881LS UT WOS:000299487500017 PM 22183819 ER PT J AU Ananthakrishnan, AN Hur, C Korzenik, JR AF Ananthakrishnan, Ashwin N. Hur, Chin Korzenik, Joshua R. TI Certolizumab Pegol Compared to Natalizumab in Patients with Moderate to Severe Crohn's Disease: Results of a Decision Analysis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Crohn's disease; Certolizumab pegol; Natalizumab; Refractory disease; Surgery; Cost-effectiveness ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; COST-EFFECTIVENESS ANALYSIS; PRIOR INFLIXIMAB THERAPY; MAINTENANCE THERAPY; CLINICAL-RESPONSE; RANDOMIZED-TRIAL; MARKOV MODEL; ADALIMUMAB; INDUCTION; REMISSION AB A significant proportion of patients with Crohn's disease (CD) lose response to antibodies directed against tumor necrosis factor alpha (TNF). Prior TNF-antagonist failure is associated with lower rates of response to subsequent TNF-antagonist therapy. In patients failing two anti-TNF agents, a choice exists between using a third-anti-TNF therapy or natalizumab (NAT), an alpha-4 integrin inhibitor. A cost-effectiveness analysis comparing these competing strategies has not been performed. A decision analytic model was constructed to compare the performance of certolizumab pegol (CZP) versus NAT in patients with moderate to severe CD. Previously published estimates of efficacy of third-line anti-TNF therapy and NAT were used to inform the model. Costs were expressed in 2010 US dollars. A 1-year time frame was used for the analysis. In the base case estimate, use of NAT was only marginally more effective [0.71 vs. 0.70 quality adjusted life-years (QALYs)] than CZP but was expensive with an incremental cost-effectiveness ratio (ICER) of $381,678 per QALY gained. For CZP 2 months response rate of at least 24%, NAT had an ICER above the willingness-to-pay (WTP) threshold. The model was sensitive to the costs of both therapies; for all CZP costs below $2,300 per dose, NAT had higher ICER than the WTP threshold. Substituting adalimumab for CZP resulted in similar ICER estimates and thresholds for NAT use. In patients with moderate to severe CD failing two TNF-antagonists, using a third TNF-antagonist therapy appears to be a cost-effective strategy without significantly compromising treatment efficacy. C1 [Ananthakrishnan, Ashwin N.; Hur, Chin; Korzenik, Joshua R.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Gastrointestinal Unit, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Hur, Chin; Korzenik, Joshua R.] Harvard Univ, Sch Med, Boston, MA USA. [Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Gastrointestinal Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org OI Hur, Chin/0000-0002-2819-7576 NR 29 TC 8 Z9 8 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 2012 VL 57 IS 2 BP 472 EP 480 DI 10.1007/s10620-011-1896-3 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 881LS UT WOS:000299487500030 PM 21909990 ER PT J AU Drummond, S Canavarro, C Perinetti, G Teles, R Capelli, J AF Drummond, S. Canavarro, C. Perinetti, G. Teles, R. Capelli, J., Jr. TI The monitoring of gingival crevicular fluid volume during orthodontic treatment: a longitudinal randomized split-mouth study SO EUROPEAN JOURNAL OF ORTHODONTICS LA English DT Article ID NECROSIS-FACTOR-ALPHA; TOOTH MOVEMENT; ALKALINE-PHOSPHATASE; PERIODONTITIS; MAGNITUDE; FLOW AB This randomized split-mouth study was aimed at evaluating whether an orthodontic appliance per se or orthodontic tooth movement can induce detectable changes in gingival crevicular fluid (GCF) volume, and thus whether GCF volume is a predictable biomarker for tissue remodelling incident to orthodontic tooth movement. Materials and Methods: Sixteen healthy orthodontic patients (7 females and 9 males; mean age, 17.7 years; range, 13-27 years) with the need for extraction of the first upper premolars were enrolled. One randomly chosen maxillary canine was subjected to a distalizing force by a 0.017 x 0.025 inch titanium-molybdenum alloy archwire and considered as the test tooth (TT). The contralateral canine, which was not subjected to any force but was included in an orthodontic appliance, was used as a control (CT). GCF sampling was performed at both mesial and distal sites of the CTs and TTs at baseline, immediately before applying the orthodontic appliance, and after 1 hour, 24 hours, and 7, 14, and 21 days. A Periotron was used to measure the GCF volume. A modest but significant increase in the GCF volume over time was seen in both the CTs (mesial sites) and the TTs (both mesial and distal sites) with no differences between the experimental teeth. Subclinical tissue inflammation consequent to the placement of the orthodontic appliance might be responsible for these GCF volume changes. The GCF volume does not appear to be a reliable biomarker for tissue remodelling during orthodontic treatment. C1 [Drummond, S.; Canavarro, C.; Capelli, J., Jr.] Univ Estado Rio De Janeiro, Dept Orthodont, Sch Dent, BR-20551030 Rio De Janeiro, Brazil. [Perinetti, G.] Univ Trieste, Dept Biomed, Sch Dent, I-34127 Trieste, Italy. [Teles, R.] Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Drummond, S (reprint author), Univ Estado Rio De Janeiro, Dept Orthodont, Sch Dent, Bl 28 Setembro 157,Sl 230 Vila Isabel, BR-20551030 Rio De Janeiro, Brazil. EM stepdrummond@yahoo.com OI Perinetti, Giuseppe/0000-0002-7226-5134 NR 29 TC 3 Z9 5 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0141-5387 J9 EUR J ORTHODONT JI Eur. J. Orthodont. PD FEB PY 2012 VL 34 IS 1 BP 109 EP 113 DI 10.1093/ejo/cjq172 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 884ZA UT WOS:000299746200018 PM 21273285 ER PT J AU Kemp, DE Karayal, ON Calabrese, JR Sachs, GS Pappadopulos, E Ice, KS Siu, CO Vieta, E AF Kemp, David E. Karayal, Onur N. Calabrese, Joseph R. Sachs, Gary S. Pappadopulos, Elizabeth Ice, Kathleen S. Siu, Cynthia O. Vieta, Eduard TI Ziprasidone with adjunctive mood stabilizer in the maintenance treatment of bipolar I disorder: Long-term changes in weight and metabolic profiles SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Metabolic syndrome; Medical comorbidity; Treatment remission; Ziprasidone ID PLACEBO-CONTROLLED TRIAL; ANTIPSYCHOTIC-DRUGS; DOUBLE-BLIND; ATYPICAL ANTIPSYCHOTICS; SERUM-CHOLESTEROL; CLINICAL-TRIAL; OPEN-LABEL; PREVALENCE; OLANZAPINE; SCHIZOPHRENIA AB This analysis was conducted to compare the effects of adjunctive ziprasidone or placebo on metabolic parameters among patients receiving maintenance treatment with lithium or valproate. We also tested whether metabolic syndrome (MetS) and other risk factors were associated with baseline characteristics and treatment response. In the stabilization phase (Phase 1), 584 bipolar I disorder (DSM-IV) patients received 2.5-4 months of open label ziprasidone (80-160 mg/d) plus lithium or valproic acid (ZIP+MS). Patients who achieved at least 8 weeks of clinical stability were subsequently randomized into Phase 2 to 6-months of double-blind treatment with ZIP+MS (n = 127) vs. placebo+MS (n=113). At baseline of Phase 1, MetS was found in 111 participants (23%). Participants with MetS (vs. non-MetS participants) were more likely to be aged 40 years or older, had significantly more severe manic symptoms, higher abdominal obesity, and higher BMI. Increase in abdominal obesity was associated with lower manic symptom improvement (p < 0.05, as assessed by MRS change score) during Phase 1, while symptom improvement differed across racial groups. In the Phase 2 double-blind phase, the ZIP+MS group had similar weight and metabolic profiles compared to the placebo+MS group across visits. These results corroborate existing findings on ziprasidone which exhibits a neutral weight and metabolic profile in the treatment of schizophrenia and bipolar patients. Our findings suggest that MetS is highly prevalent in patients with bipolar disorder, may be associated with greater manic symptom severity, and may predict treatment outcomes. (C) 2011 Elsevier B.V. and ECNP. All rights reserved. C1 [Kemp, David E.; Calabrese, Joseph R.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Karayal, Onur N.; Pappadopulos, Elizabeth; Ice, Kathleen S.] Pfizer Inc, New York, NY USA. [Sachs, Gary S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Siu, Cynthia O.] Data Power DP Inc, Dept Quantitat Methodol, Ringoes, NJ USA. [Vieta, Eduard] Univ Barcelona, Hosp Clin, IDIBAPS, CIBERSAM, Barcelona, Spain. RP Kemp, DE (reprint author), Case Western Reserve Univ, Univ Hosp Case Med Ctr, 10524 Euclid Ave,12th Floor, Cleveland, OH 44106 USA. EM kemp.david@gmail.com RI Vieta, Eduard/I-6330-2013 OI Vieta, Eduard/0000-0002-0548-0053 FU Pfizer, Inc.; Abbott; AstraZeneca; Bristol-Myers Squibb; France Foundation; GlaxoSmithKline; Janssen; Johnson Johnson; Eli Lilly Et Co.; Pfizer; Servier; Solvay/Wyeth; Abott laboratories; Cephalon; Eli Lilly; Glaxo-Smith-Kline; Memory Pharmaceuticals; Merck; Novartis; Shering-Plough; Otsuka; Repligen; Sanofi-Aventis; Sepracor; Shire; Solvay; Wyeth; Almirall; Forest Research Institute; Geodon Richter; Janssen-Cilag; Jazz; Lundbeck; Organon; Pierre-Fabre; Qualigen; Takeda; United Biosource Corporation; Spanish Ministry of Science and Innovation (CIBERSAM); Seventh European Framework Programme (ENBREC) FX This study was sponsored by Pfizer, Inc. The sponsor was involved in all stages from conception, analysis, to review of the manuscript. Data analysis was supported by Pfizer, Inc., and interpreted collectively by all of the authors. The decision to submit the paper for publication was made by all co-authors.; DEK has acted as a consultant to Bristol-Myers Squibb and has served on a speakers bureau for AstraZeneca and Pfizer. JRC has received research support, acted as a consultant, and/or served on an advisory board for Abbott, AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen, Johnson & Johnson, Eli Lilly Et Co., Pfizer, Servier, and Solvay/Wyeth. GSS has received research support from Abott laboratories, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Glaxo-Smith-Kline, Janssen, Johnson & Johnson, Memory Pharmaceuticals, Merck, Novartis, Shering-Plough, Otsuka, Pfizer, Repligen, Sanofi-Aventis, Sepracor, Shire, Solvay, and Wyeth. GSS is a stockholder of Concordant Rater Systems. EV has received research support, acted as a consultant, and/or served on an advisory board for Almirall, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest Research Institute, Geodon Richter, Glaxo-Smith-Kline, Janssen-Cilag, Jazz, Lundbeck, Merck, Novartis, Organon, Otsuka, Pfizer, Pierre-Fabre, Qualigen, Sanofi-Aventis, Servier, Shering-Plough, Solvay, Takeda, United Biosource Corporation, and Wyeth. EV has received grants from Almirall, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest, Glaxo-Smith-Kline, Janssen-Cilag, Otsuka, Pfizer, Sanofi-Aventis, Servier, Shering-Plough, the Spanish Ministry of Science and Innovation (CIBERSAM), the Seventh European Framework Programme (ENBREC), United Biosource Corporation, and Wyeth. COS was a paid consultant to Pfizer in connection with the statistical analysis and development of this manuscript and has served as a consultant to Pfizer, Dainippon Sumitomo Pharma/Sepracor, Memory Pharmaceutical/Roche Laboratories, and Wyeth over the past 3 years. ONK, EP, and KSI are full time employees of Pfizer, Inc. NR 52 TC 14 Z9 14 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD FEB PY 2012 VL 22 IS 2 BP 123 EP 131 DI 10.1016/j.euroneuro.2011.06.005 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 884PT UT WOS:000299720700005 PM 21798721 ER PT J AU Nitsche, C Edderkaoui, M Moore, RM Eibl, G Kasahara, N Treger, J Grippo, PJ Mayerle, J Lerch, MM Gukovskaya, AS AF Nitsche, Claudia Edderkaoui, Mouad Moore, Ryan M. Eibl, Guido Kasahara, Noriyuki Treger, Janet Grippo, Paul J. Mayerle, Julia Lerch, Markus M. Gukovskaya, Anna S. TI The Phosphatase PHLPP1 Regulates Akt2, Promotes Pancreatic Cancer Cell Death, and Inhibits Tumor Formation SO GASTROENTEROLOGY LA English DT Article DE ROS; NADPH Oxidase; Apoptosis; Tumor Progression ID KINASE-B ACTIVATION; TYROSINE PHOSPHATASES; DUCTAL ADENOCARCINOMA; SIGNALING PATHWAY; NADPH OXIDASE; K-RAS; APOPTOSIS; PROTEIN; GROWTH; EXPRESSION AB BACKGROUND & AIMS: The kinase Akt mediates resistance of pancreatic cancer (PaCa) cells to death and is constitutively active (phosphorylated) in cancer cells. Whereas the kinases that activate Akt are well characterized, less is known about phosphatases that dephosporylate and thereby inactivate it. We investigated regulation of Akt activity and cell death by the phosphatases PHLPP1 and PHLPP2 in PaCa cells, mouse models of PaCa, and human pancreatic ductal adenocarcinoma (PDAC). METHODS: We measured the effects of PHLPP overexpression or knockdown with small interfering RNAs on Akt activation and cell death. We examined regulation of PHLPPs by growth factors and reactive oxygen species, as well as associations between PHLPPs and tumorigenesis. RESULTS: PHLPP overexpression inactivated Akt, whereas PHLPP knockdown increased phosphorylation of Akt in PaCa cells. Levels of PHLPPs were greatly reduced in human PDAC and in mouse genetic and xenograft models of PaCa. PHLPP activities in PaCa cells were down-regulated by growth factors and Nox4 reduced nicotinamide adenine dinucleotide phosphate oxidase. PHLPP1 selectively dephosphorylated Akt2, whereas PHLPP2 selectively dephosphorylated Akt1. Akt2, but not Akt1, was up-regulated in PDAC, and Akt2 levels correlated with mortality. Consistent with these results, high levels of PHLPP1, which dephosphorylates Akt2 (but not PHLPP2, which dephosphorylates Akt1), correlated with longer survival times of patients with PDAC. In mice, xenograft tumors derived from PaCa cells that overexpress PHLPP1 (but not PHLPP2) had inactivated Akt, greater extent of apoptosis, and smaller size. CONCLUSIONS: PHLPP1 has tumor suppressive activity and might represent a therapeutic or diagnostic tool for PDAC. C1 [Nitsche, Claudia; Edderkaoui, Mouad; Moore, Ryan M.; Gukovskaya, Anna S.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Nitsche, Claudia; Edderkaoui, Mouad; Moore, Ryan M.; Kasahara, Noriyuki; Treger, Janet; Gukovskaya, Anna S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Eibl, Guido] Univ Calif Los Angeles, Dept Surg, Hirshberg Lab Translat Pancreat Canc Res, Los Angeles, CA 90024 USA. [Nitsche, Claudia; Mayerle, Julia; Lerch, Markus M.] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med A, Greifswald, Germany. [Grippo, Paul J.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. RP Gukovskaya, AS (reprint author), UCLA VA Greater Los Angeles, Pancreat Res Grp, W Los Angeles VA Healthcare Ctr, 11308 Wilshire Blvd,Bldg 258,Room 340, Los Angeles, CA USA. EM agukovsk@ucla.edu RI Lerch, Markus M./E-2206-2016 OI Lerch, Markus M./0000-0002-9643-8263 FU National Cancer Institute [R01CA119025]; Department of Veterans Affairs Merit Review; Alfried Krupp von Bohlen und Halbach Stiftung grant FX Supported by National Cancer Institute grant R01CA119025 and the Department of Veterans Affairs Merit Review (to A. S. G.) and the Alfried Krupp von Bohlen und Halbach Stiftung grant (to C.N.). NR 34 TC 32 Z9 33 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2012 VL 142 IS 2 BP 377 EP U296 DI 10.1053/j.gastro.2011.10.026 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 882CV UT WOS:000299540000044 PM 22044669 ER PT J AU Castillo, JG Telem, D Heimann, TM AF Castillo, Javier G. Telem, Dana Heimann, Tomas M. TI An Extremely Unusual and Large Cause of Anemia SO GASTROENTEROLOGY LA English DT Editorial Material ID ANGIOSARCOMA C1 [Castillo, Javier G.] James J Peters VA Med Ctr, Dept Thorac Surg, Bronx, NY USA. [Telem, Dana; Heimann, Tomas M.] James J Peters VA Med Ctr, Dept Gen Surg, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. RP Castillo, JG (reprint author), James J Peters VA Med Ctr, Dept Thorac Surg, Bronx, NY USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2012 VL 142 IS 2 BP E23 EP E24 DI 10.1053/j.gastro.2011.03.067 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 882CV UT WOS:000299540000011 PM 22197165 ER PT J AU Puli, SR Spofford, IS Thompson, CC AF Puli, Srinivas R. Spofford, Inbar S. Thompson, Christopher C. TI Use of self-expandable stents in the treatment of bariatric surgery leaks: a systematic review and meta-analysis SO GASTROINTESTINAL ENDOSCOPY LA English DT Review ID ROUX-EN-Y; LAPAROSCOPIC GASTRIC BYPASS; ANASTOMOTIC LEAKS; HEALTH-CARE; SLEEVE GASTRECTOMY; EXPANDING STENTS; CLINICAL-TRIALS; MORBID-OBESITY; COMPLICATIONS; MANAGEMENT AB Background: Bariatric surgery leaks can result in significant morbidity and mortality. Endoscopic placement of self-expandable stents (SESs) is emerging as a less-invasive alternative to surgery for the treatment of leaks. Objective: To evaluate the success of SESs in the treatment of bariatric surgery leaks. Design: Studies using SESs in the management of bariatric surgery leaks were selected. Success of SES treatment was defined as radiographic evidence of leak closure after stent removal. Articles were searched in MEDLINE, PubMed, Ovid, and Cochrane Register of Controlled Trials. Pooled proportions were calculated by using fixed- and random-effects models. Publication bias was calculated by using the Begg-Mazumdar and Harbord bias estimators. Results: A total of 189 relevant articles were reviewed of which 7 studies (67 patients with leaks) met inclusion criteria. The pooled proportion of successful leak closures by using SESs was 87.77% (95% CI, 79.39%-94.19%). The pooled proportion of successful endoscopic stent removal was 91.57% (95% CI, 84.22%-96.77%). Stent migration was noted in 16.94% (95% CI, 9.32%-26.27%). Test of heterogeneity gave a P value >.10. There was no publication bias. Limitations: Small retrospective studies, different types of stents used. Conclusion: Endoscopic placement of SESs is a minimally invasive, safe, and effective alternative in the management of leaks after bariatric surgery. The use of SESs can minimize the need for surgical revision and improve patient outcomes. (Gastrointest.Endosc 2012;75:287-93.) C1 [Puli, Srinivas R.; Spofford, Inbar S.; Thompson, Christopher C.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Spofford, Inbar S.] Massachusetts Gen Hosp, Div Pediat Gastroenterol, Boston, MA 02114 USA. RP Thompson, CC (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. NR 43 TC 46 Z9 52 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 2012 VL 75 IS 2 BP 287 EP 293 DI 10.1016/j.gie.2011.09.010 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 885BF UT WOS:000299752800009 PM 22047699 ER PT J AU Yoon, WJ Brugge, WR AF Yoon, Won Jae Brugge, William R. TI EUS-guided biliary rendezvous: EUS to the rescue SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID BILE-DUCT CANNULATION; PRE-CUT PAPILLOTOMY; DRAINAGE; ERCP C1 [Yoon, Won Jae; Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Yoon, WJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. NR 17 TC 4 Z9 5 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 2012 VL 75 IS 2 BP 360 EP 361 DI 10.1016/j.gie.2011.09.024 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 885BF UT WOS:000299752800018 PM 22248604 ER PT J AU Jensen, DM AF Jensen, Dennis M. TI The ins and outs of diverticular bleeding SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID SEVERE HEMATOCHEZIA; URGENT COLONOSCOPY; HEMORRHAGE; DIAGNOSIS C1 [Jensen, Dennis M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Jensen, Dennis M.] Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA USA. [Jensen, Dennis M.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Jensen, Dennis M.] CURE Digest Dis Res Ctr, Los Angeles, CA USA. RP Jensen, DM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. FU NIADDK NIH HHS [AM 41301] NR 10 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 2012 VL 75 IS 2 BP 388 EP 391 DI 10.1016/j.gie.2011.09.004 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 885BF UT WOS:000299752800022 PM 22248606 ER PT J AU Kostic, AD Gevers, D Pedamallu, CS Michaud, M Duke, F Earl, AM Ojesina, AI Jung, J Bass, AJ Tabernero, J Baselga, J Liu, C Shivdasani, RA Ogino, S Birren, BW Huttenhower, C Garrett, WS Meyerson, M AF Kostic, Aleksandar D. Gevers, Dirk Pedamallu, Chandra Sekhar Michaud, Monia Duke, Fujiko Earl, Ashlee M. Ojesina, Akinyemi I. Jung, Joonil Bass, Adam J. Tabernero, Josep Baselga, Jose Liu, Chen Shivdasani, Ramesh A. Ogino, Shuji Birren, Bruce W. Huttenhower, Curtis Garrett, Wendy S. Meyerson, Matthew TI Genomic analysis identifies association of Fusobacterium with colorectal carcinoma SO GENOME RESEARCH LA English DT Article ID HELICOBACTER-PYLORI; EPITHELIAL-CELLS; COLON-CANCER; PERSPECTIVE; MICROBIOTA; BACTERIA; RESOURCE; DISEASE AB The tumor microenvironment of colorectal carcinoma is a complex community of genomically altered cancer cells, nonneoplastic cells, and a diverse collection of microorganisms. Each of these components may contribute to carcinogenesis; however, the role of the microbiota is the least well understood. We have characterized the composition of the microbiota in colorectal carcinoma using whole genome sequences from nine tumor/normal pairs. Fusobacterium sequences were enriched in carcinomas, confirmed by quantitative PCR and 16S rDNA sequence analysis of 95 carcinoma/normal DNA pairs, while the Bacteroidetes and Firmicutes phyla were depleted in tumors. Fusobacteria were also visualized within colorectal tumors using FISH. These findings reveal alterations in the colorectal cancer microbiota; however, the precise role of Fusobacteria in colorectal carcinoma pathogenesis requires further investigation. C1 [Kostic, Aleksandar D.; Gevers, Dirk; Pedamallu, Chandra Sekhar; Duke, Fujiko; Earl, Ashlee M.; Ojesina, Akinyemi I.; Jung, Joonil; Bass, Adam J.; Birren, Bruce W.; Huttenhower, Curtis; Garrett, Wendy S.; Meyerson, Matthew] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02142 USA. [Kostic, Aleksandar D.; Ogino, Shuji; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Pedamallu, Chandra Sekhar; Duke, Fujiko; Ojesina, Akinyemi I.; Bass, Adam J.; Shivdasani, Ramesh A.; Ogino, Shuji; Garrett, Wendy S.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Michaud, Monia; Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Tabernero, Josep; Baselga, Jose] Univ Autonoma Barcelona, Dept Med Oncol, Vall dHebron Univ Hosp, Barcelona 08035, Spain. [Liu, Chen] Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32610 USA. [Liu, Chen] Univ Florida, Coll Med, Dept Immunol, Gainesville, FL 32610 USA. [Liu, Chen] Univ Florida, Coll Med, Dept Lab Med, Gainesville, FL 32610 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02142 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI Ojesina, Akinyemi/0000-0003-0755-3639; Earl, Ashlee/0000-0001-7857-9145; Kostic, Aleksandar/0000-0002-0837-4360; Huttenhower, Curtis/0000-0002-1110-0096 FU National Human Genome Research Institute [U54HG003067]; National Cancer Institute [P50CA127003, RC2CA148317, R01CA154426]; Starr Cancer Consortium; Natural Sciences and Engineering Research Council of Canada; Albert J. Ryan Foundation; Damon Runyon Cancer Research Foundation FX This work was funded by grants from the National Human Genome Research Institute (U54HG003067), The National Cancer Institute (P50CA127003; RC2CA148317; R01CA154426), and the Starr Cancer Consortium. A.D.K. was supported by a Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarship and an Albert J. Ryan Foundation Fellowship. A.I.O. was supported by the Rebecca Ridley Kry Fellowship of the Damon Runyon Cancer Research Foundation. We thank Jordi Barretina, Kristin Ardlie, Candace Guidicci, Lauren Ambrogio, and Susanna Hamilton of the Broad Institute and Emma Allen-Vercoe of the University of Guelph for assistance and advice. NR 28 TC 333 Z9 347 U1 9 U2 70 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD FEB PY 2012 VL 22 IS 2 BP 292 EP 298 DI 10.1101/gr.126573.111 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 883BA UT WOS:000299606400012 PM 22009990 ER PT J AU Dewal, N Hu, Y Freedman, ML LaFramboise, T Pe'er, I AF Dewal, Ninad Hu, Yang Freedman, Matthew L. LaFramboise, Thomas Pe'er, Itsik TI Calling amplified haplotypes in next generation tumor sequence data SO GENOME RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; COPY-NUMBER ALTERATIONS; DIFFERENTIAL EXPRESSION ANALYSIS; OVARIAN-CANCER SUSCEPTIBILITY; HIDDEN MARKOV MODEL; BREAST-CANCER; STRUCTURAL VARIATION; PROSTATE-CANCER; MYELOPROLIFERATIVE NEOPLASMS; COLORECTAL-CANCER AB During tumor initiation and progression, cancer cells acquire a selective advantage, allowing them to outcompete their normal counterparts. Identification of the genetic changes that underlie these tumor acquired traits can provide deeper insights into the biology of tumorigenesis. Regions of copy number alterations and germline DNA variants are some of the elements subject to selection during tumor evolution. Integrated examination of inherited variation and somatic alterations holds the potential to reveal specific nucleotide alleles that a tumor "prefers" to have amplified. Next-generation sequencing of tumor and matched normal tissues provides a high-resolution platform to identify and analyze such somatic amplicons. Within an amplicon, examination of informative (e.g., heterozygous) sites deviating from a 1:1 ratio may suggest selection of that allele. A naive approach examines the reads for each heterozygous site in isolation; however, this ignores available valuable linkage information across sites. We, therefore, present a novel hidden Markov model-based method Haplotype Amplification in Tumor Sequences (HATS) that analyzes tumor and normal sequence data, along with training data for phasing purposes, to infer amplified alleles and haplotypes in regions of copy number gain. Our method is designed to handle rare variants and biases in read data. We assess the performance of HATS using simulated amplified regions generated from varying copy number and coverage levels, followed by amplicons in real data. We demonstrate that HATS infers the amplified alleles more accurately than does the naive approach, especially at low to intermediate coverage levels and in cases (including high coverage) possessing stromal contamination or allelic bias. C1 [Hu, Yang; Pe'er, Itsik] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA. [Dewal, Ninad] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA. [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freedman, Matthew L.] Broad Inst Harvard & MIT, Med & Populat Genet Program, Cambridge, MA 02142 USA. [LaFramboise, Thomas] Case Western Reserve Univ, Dept Genet, Sch Med, Cleveland, OH 44106 USA. RP Pe'er, I (reprint author), Columbia Univ, Dept Comp Sci, New York, NY 10027 USA. EM itsik@cs.columbia.edu FU National Institutes of Health and National Library of Medicine [5T15 LM007079-14]; National Institutes of Health [CA131341-01A1] FX This work was supported by the National Institutes of Health and National Library of Medicine (5T15 LM007079-14 to the Medical Informatics Research Training Program, Department of Biomedical Informatics, Columbia University); and the National Institutes of Health (1 R01 CA131341-01A1). The results published here are, in part, based upon data generated by The Cancer Genome Atlas pilot project established by the NCI and NHGRI. Information about TCGA, the investigators, and institutions that constitute the TCGA research network can be found at http://cancergenome.nih.gov. The results here are also, in part, based upon data generated by the 1000 Genomes Project. Information about the 1000 Genomes Project, along with participating investigators and institutions, can be found at http://www.1000genomes.org. NR 92 TC 4 Z9 4 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD FEB PY 2012 VL 22 IS 2 BP 362 EP 374 DI 10.1101/gr.122564.111 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 883BA UT WOS:000299606400019 PM 22090379 ER PT J AU Manchanda, R Drapkin, R Jacobs, I Menon, U AF Manchanda, Ranjit Drapkin, Ronny Jacobs, Ian Menon, Usha TI The role of peritoneal cytology at risk-reducing salpingo-oophorectomy (RRSO) in women at increased risk of familial ovarian/tubal cancer SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID BRCA MUTATION CARRIERS; PRIMARY FALLOPIAN-TUBE; PROPHYLACTIC OOPHORECTOMY; CARCINOMA; SPECIMENS; ADENOCARCINOMA; SURGERY C1 [Manchanda, Ranjit; Jacobs, Ian; Menon, Usha] UCL, EGA Inst Womens Hlth, Gynaecol Canc Res Ctr, Dept Gynaecol Oncol, London W1T 7DN, England. [Drapkin, Ronny] Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Jacobs, Ian] Univ Manchester, Fac Med & Human Sci, Manchester M13 9PT, Lancs, England. RP Menon, U (reprint author), EGA Inst Womens Hlth, Gynaecol Canc Res Ctr, 1st Floor,Maple House,149 Tottenham Court Rd, London W1T 7NF, England. EM u.menon@ucl.ac.uk RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 24 TC 14 Z9 15 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2012 VL 124 IS 2 BP 185 EP 191 DI 10.1016/j.ygyno.2011.10.017 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 885UE UT WOS:000299805500003 PM 22019526 ER PT J AU Kalogera, E Scholler, N Powless, C Weaver, A Drapkin, R Li, JP Jiang, SW Podratz, K Urban, N Dowdy, SC AF Kalogera, Eleftheria Scholler, Nathalie Powless, Cecelia Weaver, Amy Drapkin, Ronny Li, Jinping Jiang, Shi-Wen Podratz, Karl Urban, Nicole Dowdy, Sean C. TI Correlation of serum HE4 with tumor size and myometrial invasion in endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Endometrial cancer; Human epididymis protein 4 (HE4); Tumor marker ID OVARIAN-CARCINOMA; HUMAN EPIDIDYMIS; CA 125; PELVIC LYMPHADENECTOMY; PROTEINASE-INHIBITORS; MASS-SPECTROMETRY; BREAST-CANCER; EARLY-STAGE; FOLLOW-UP; EXPRESSION AB Objective. To evaluate the utility of serum (HE4) as a marker for high risk disease in patients with endometrial cancer (EC). Methods. Preoperative serum HE4 levels were measured from a cohort of 75 patients surgically treated for EC. Cases were compared to matched controls without a history of cancer. HE4 levels were analyzed as a function of primary tumor diameter, grade, stage and histological subtype. Wilcoxon rank-sum test, ROC curve, Spearman rank correlation coefficient and contingency tables were used for statistical analyses. Results. Stage distribution was as follows: 49 stage I, 2 stage II, 20 stage III, 4 stage IV. Type I EC was present in 54 patients, type II in 21. Median HE4 was significantly elevated in both types land II EC compared to controls (P<0.001 and P=0.019, respectively). There was significant correlation between type I EC, median HE4, deep myometrial invasion (MI) (>50%, P<0.001) and primary tumor diameter (PTD) (>2 cm, P=0.002). Low risk patients (type I, MI <= 50% and PTD <= 2 cm) had significantly lower median HE4 compared to all other type I EC patients (P<0.01). In comparison to prior investigations, HE4 (cutoff of 8 mfi) was more sensitive than CA125 in detecting advanced stage disease. Conclusion. Our data suggest that HE4 is elevated in a high proportion of EC patients, is correlated with PTD and MI, and is more sensitive than CA125 in EC. These observations suggest potential utility of HE4 in the preoperative prediction of high risk disease and the necessity for definitive surgical staging. (C) 2011 Elsevier Inc. All rights reserved. C1 [Kalogera, Eleftheria; Powless, Cecelia; Li, Jinping; Jiang, Shi-Wen; Podratz, Karl; Dowdy, Sean C.] Mayo Clin, Div Gynecol Surg, Rochester, MN USA. [Scholler, Nathalie] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Weaver, Amy] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA. [Drapkin, Ronny] Dana Farber Canc Inst, Boston, MA 02115 USA. [Urban, Nicole] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Dowdy, SC (reprint author), 200 1st St SW, Rochester, MN 55905 USA. EM dowdy.sean@mayo.edu RI Scholler, Nathalie/O-9003-2014; Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU NIH/NCI MD Anderson Uterine Cancer SPORE [NIH 2P50 CA098258-06] FX This study is supported by the Career Development Program of the NIH/NCI MD Anderson Uterine Cancer SPORE (NIH 2P50 CA098258-06 SPORE in Uterine Cancer, Pls: Karen H. Lu and Russel R. Broaddus) (J. Li, mentors: S. Jiang, K. Podratz, R. Broaddus). NR 55 TC 33 Z9 36 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2012 VL 124 IS 2 BP 270 EP 275 DI 10.1016/j.ygyno.2011.10.025 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 885UE UT WOS:000299805500018 PM 22037318 ER PT J AU Emmons, KM Weiner, B Fernandez, ME Tu, SP AF Emmons, Karen M. Weiner, Bryan Fernandez, Maria Eulalia Tu, Shin-Ping TI Systems Antecedents for Dissemination and Implementation: A Review and Analysis of Measures SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE cancer prevention and screening; chronic disease management; health promotion; research design; work site health promotion ID WORK-ENVIRONMENT PERCEPTIONS; HEALTH-CARE; ORGANIZATIONAL READINESS; SCHOOL CLIMATE; ABSORPTIVE-CAPACITY; QUALITY IMPROVEMENT; BALANCED SCORECARD; IMAGING TECHNOLOGY; TEAM EFFECTIVENESS; SMOKING POLICIES AB There is a growing emphasis on the role of organizations as settings for dissemination and implementation. Only recently has the field begun to consider features of organizations that affect dissemination and implementation of evidence-based interventions. This manuscript identifies and evaluates available measures for five key organizational-level constructs: (a) leadership, (b) vision, (c) managerial relations, (d) climate, and (e) absorptive capacity. Overall the picture was the same across the five constructs-no measure was used in more than one study, many studies did not report the psychometric properties of the measures, some assessments were based on a single response per unit, and the level of the instrument and analysis did not always match. One must seriously consider the development and evaluation of a robust set of measures that will serve as the basis of building the field, allow for comparisons across organizational types and intervention topics, and allow a robust area of dissemination and implementation research to develop. C1 [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Weiner, Bryan] Univ N Carolina, Chapel Hill, NC USA. [Fernandez, Maria Eulalia] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Tu, Shin-Ping] Univ Washington, Seattle, WA 98195 USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, 44 Binney St,LW706, Boston, MA 02115 USA. EM karen_m_emmons@dfci.harvard.edu FU NCCDPHP CDC HHS [U48-DP001911, U48 DP000057, U48 DP000059, U48 DP001911, U48 DP001944, U48 DP001946, U48-DP000057, U48-DP001946, U48/DP000059, U48/DP001944]; NCI NIH HHS [1K05 CA124415-01A1, K05 CA124415, K05 CA124415-05, R01 CA123228, R01 CA123228-05, R01 CA124397, R01 CA124397-05, R01 CA124402, R01 CA124402-05] NR 85 TC 22 Z9 23 U1 3 U2 24 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD FEB PY 2012 VL 39 IS 1 BP 87 EP 105 DI 10.1177/1090198111409748 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 885LN UT WOS:000299780600010 PM 21724933 ER PT J AU Santacana, M Yeramian, A Velasco, A Bergada, L Gatius, S Garcia, V Azueta, A Palacios, J Dolcet, X Oliva, E Matias-Guiu, X AF Santacana, Maria Yeramian, Andree Velasco, Ana Bergada, Laura Gatius, Sonia Garcia, Virginia Azueta, Ainara Palacios, Jose Dolcet, Xavier Oliva, Esther Matias-Guiu, Xavier TI Immunohistochemical features of post-radiation vaginal recurrences of endometrioid carcinomas of the endometrium: role for proteins involved in resistance to apoptosis and hypoxia SO HISTOPATHOLOGY LA English DT Article DE apoptosis; endometrial carcinoma; hypoxia; tissue microarray; vaginal recurrence ID KAPPA-B; MICROSATELLITE INSTABILITY; RADIATION-RESISTANCE; TISSUE MICROARRAY; POOR-PROGNOSIS; BETA-CATENIN; MUTATIONS; EXPRESSION; CELLS; PTEN AB Aims: Endometrioid carcinoma of the endometrium (EEC) is treated with surgery and radiotherapy. Postradiation recurrences are associated with increased risk of metastases. Comparison of the expression of genes important in the development and progression of EEC, and others involved in resistance to apoptosis and hypoxia and adaptation to radiation, was performed between post-radiation vaginal recurrences (PVRs) and primary EECs. We tried to reproduce the results by exposing an EEC cell line to hypoxia and radiation. Methods and results: Immunohistochemistry and tissue microarrays were used to compare 24 PVRs with 82 primary EECs. PVRs exhibited increased expression of p53 (P < 0.0001), cytoplasmic FLICE-inhibitory protein (FLIP) (P < 0.0001), and Ki67 (P < 0.0001), and nuclear staining for FLIP, nuclear factor kappaB (NF-kappa B) family members (p50, P < 0.0001; c-Rel, P = 0.0077; RelB, P = 0.0157), and beta-catenin (P = 0.0001). Differences regarding p50, hypoxia-inducible factor 1 alpha (HIF-1 alpha), and cytoplasmic FLIP were statistically significant when PVRs and primary EECs were matched for histological grade. Exposure of the EEC cell line to hypoxia induced nuclear expression of beta-catenin, FLIP, and HIF-1 alpha, as well as increased NF-kappa B activity. No changes in FLIP, HIF-1 alpha or NF-kappa B were seen when cells were exposed to radiation. Nuclear expression of b-catenin was seen at 3 Gy, but not at 1 Gy. Conclusions: Genes involved in resistance to hypoxia are expressed in PVRs, and may play a role in the development of post-radiation recurrences. C1 [Santacana, Maria; Yeramian, Andree; Velasco, Ana; Bergada, Laura; Gatius, Sonia; Garcia, Virginia; Azueta, Ainara; Dolcet, Xavier; Matias-Guiu, Xavier] Univ Lleida, Dept Pathol & Mol Genet, Hosp Univ Arnau de Vilanova, IRBLLEIDA, Lleida 25198, Spain. [Santacana, Maria; Yeramian, Andree; Velasco, Ana; Bergada, Laura; Gatius, Sonia; Garcia, Virginia; Azueta, Ainara; Dolcet, Xavier; Matias-Guiu, Xavier] Univ Lleida, Res Lab, Hosp Univ Arnau de Vilanova, IRBLLEIDA, Lleida 25198, Spain. [Azueta, Ainara; Palacios, Jose] Hosp Virgen Rocio, Seville, Spain. [Oliva, Esther] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Matias-Guiu, X (reprint author), Univ Lleida, Dept Pathol & Mol Genet, Hosp Univ Arnau de Vilanova, IRBLLEIDA, Av Alcalde Rovira Roure 80, Lleida 25198, Spain. EM xmatias@arnau.scs.es RI matias-guiu, xavier/C-3039-2009; Dolcet, Xavi/B-5665-2009; OI matias-guiu, xavier/0000-0002-7201-6605; VELASCO, ANA/0000-0003-3142-145X FU Instituto Carlos III; Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo [CP05/00028]; Ministerio de Ciencia e Innovacion [JCI-2008-1969]; Fundacion Alicia Cuello de Merigo; Xarxa catalana de Bancs de Tumors; Tumour Bank Platform of RTICC; [FIS PI070276]; [FIS PI100922]; [FIS PI070304]; [Marato de TV3 2005-7]; [2009SGR794]; [RD06/0020/0013]; [RD06/0020/1034]; [RD09/0076/00059] FX This work was supported by grants FIS PI070276, FIS PI100922, FIS PI070304, Marato de TV3 2005-7, 2009SGR794, RD06/0020/0013, RD06/0020/1034 and programa de intensificacion de la investigacion, Instituto Carlos III. X. Dolcet holds a postdoctoral fellowship from Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo (CP05/00028). A. Yeramian holds a postdoctoral fellowship from Programa Juan de la Cierva, Ministerio de Ciencia e Innovacion (JCI-2008-1969). L. Bergada holds a fellowship from Fundacion Alicia Cuello de Merigo. Tumour samples were obtained with the support of Xarxa catalana de Bancs de Tumors, the Tumour Bank Platform of RTICC and RD09/0076/00059. NR 37 TC 8 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD FEB PY 2012 VL 60 IS 3 BP 460 EP 471 DI 10.1111/j.1365-2559.2011.04106.x PG 12 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 882HC UT WOS:000299553400009 PM 22276609 ER PT J AU Wang, SA Hasserjian, RP AF Wang, Sa A. Hasserjian, Robert P. TI Erythroid proliferations in myeloid neoplasms SO HUMAN PATHOLOGY LA English DT Article DE Erythroid; Myelodysplastic syndromes; Acute erythroleukemia; Pure erythroid leukemia, cytogenetics; Survival ID WORLD-HEALTH-ORGANIZATION; MYELODYSPLASIA-RELATED CHANGES; BONE-MARROW; ACUTE ERYTHROLEUKEMIA; SIDEROBLASTIC ANEMIA; PROGNOSTIC-SIGNIFICANCE; MULTILINEAGE DYSPLASIA; LYMPHOID-TISSUES; POOR-PROGNOSIS; CLASSIFICATION AB Prominent erythroid proliferations (in which erythroid elements comprise >= 50% of total bone marrow cells) can be seen in various hematopoietic stem cell neoplasms. The myeloproliferative neoplasm polycythemia vera exhibits effective, overexuberant erythropoiesis resulting in an increased red blood cell mass; in contrast, most other diseases characterized by erythroid predominance exhibit ineffective hemopoiesis. The latter include acute erythroid leukemia (erythroid-myeloid and pure erythroid leukemia subtypes) as well as some cases of myelodysplastic syndromes, acute myeloid leukemia with myelodysplasia-related changes, and therapy-related myeloid neoplasms. Some nonneoplastic reactive conditions may also manifest a striking bone marrow erythroid predominance. In this article, we review the literature relevant to this group of diseases for a better understanding of their clinicopathologic features and surrounding controversies. We also examine the position of neoplastic erythroid proliferations in the current 2008 World Health Organization Classification of Myeloid Neoplasms and provide recommendations as to how to approach the differential diagnosis of this group of diseases. (C) 2012 Elsevier Inc. All rights reserved. C1 [Wang, Sa A.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Wang, SA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. EM swang5@mdanderson.org FU NCI NIH HHS [P30 CA016672] NR 65 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2012 VL 43 IS 2 BP 153 EP 164 DI 10.1016/j.humpath.2011.08.008 PG 12 WC Pathology SC Pathology GA 885GL UT WOS:000299766600001 PM 22154053 ER PT J AU Meng, R Konakondla, S Wang, XY Lo, EH Ding, YC Ji, XM AF Meng, Ran Konakondla, Sanjay Wang, Xiaoying Lo, Eng H. Ding, Yuchuan Ji, Xunming TI Plasma biomarker may help to distinguish acute CVST from non-thrombotic CVSS in emergency SO INTERNATIONAL JOURNAL OF STROKE LA English DT Letter C1 [Meng, Ran; Ji, Xunming] Capital Med Univ, China Amer Joint Inst Neurosci, Cerebral Vasc Dis Res Inst, Xuanwu Hosp,Key Lab Neurodegenerat Dis,Minist Edu, Beijing 100053, Peoples R China. [Meng, Ran] Peking Univ, Capital Med Univ, Beijing Shijitan Hosp, Dept Neurol,Clin Med Coll 9, Beijing 100871, Peoples R China. [Meng, Ran; Wang, Xiaoying; Lo, Eng H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Konakondla, Sanjay; Ding, Yuchuan] Wayne State Univ, Sch Med, Dept Neurosurg, Detroit, MI USA. RP Ji, XM (reprint author), Capital Med Univ, China Amer Joint Inst Neurosci, Cerebral Vasc Dis Res Inst, Xuanwu Hosp,Key Lab Neurodegenerat Dis,Minist Edu, 45 Changchum St, Beijing 100053, Peoples R China. EM jixm70@hotmail.com FU NINDS NIH HHS [RC2 NS069335, P01 NS055104] NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD FEB PY 2012 VL 7 IS 2 BP 183 EP 184 DI 10.1111/j.1747-4949.2011.00746.x PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 879MS UT WOS:000299334600016 PM 22264373 ER PT J AU Mukinda, FK Theron, D van der Spuy, GD Jacobson, KR Roscher, M Streicher, EM Musekiwa, A Coetzee, GJ Victor, TC Marais, BJ Nachega, JB Warren, RM Schaaf, HS AF Mukinda, F. K. Theron, D. van der Spuy, G. D. Jacobson, K. R. Roscher, M. Streicher, E. M. Musekiwa, A. Coetzee, G. J. Victor, T. C. Marais, B. J. Nachega, J. B. Warren, R. M. Schaaf, H. S. TI Rise in rifampicin-monoresistant tuberculosis in Western Cape, South Africa SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE rifampicin; monoresistant; tuberculosis; South Africa ID RESISTANT MYCOBACTERIUM-TUBERCULOSIS; HIV-INFECTED PATIENTS; NEW-YORK-CITY; PHARMACOKINETICS; MALABSORPTION; DIAGNOSIS; ORIGIN AB SETTING : Brewelskloof Hospital, Western Cape, South Africa. OBJECTIVES: To verify the perceived increase in rifampicin monoresistant tuberculosis (RMR-TB) in the Cape Winelands-Overberg region and to identify potential risk factors. DESIGN: A retrospective descriptive study of trends in RMR-TB over a 5-year period (2004-2008), followed by a case-control study of RMR and isoniazid (INH) monoresistant TB cases, diagnosed from April 2007 to March 2009, to assess for risk factors. RESULTS: The total number of RMR-TB cases more than tripled, from 31 in 2004 to 98 in 2008. The calculated doubling time was 1.63 years (95%CI 1.18-2.66). For the assessment of risk factors, 95 RMR-TB cases were objectively verified on genotypic and phenotypic analysis. Of 108 specimens genotypically identified as RMR cases, 13 (12%) were misidentified multidrug-resistant TB. On multivariate analysis, previous use of antiretroviral therapy (OR 6.4, 95%CI 1.3-31.8), alcohol use (OR 4.8, 95%CI 2.0-11.3) and age >= 40 years (OR 5.8, 95%CI 2.4-13.6) were significantly associated with RMR-TB. CONCLUSION: RMR-TB is rapidly increasing in the study setting, particularly among patients with advanced human immunodeficiency virus (HIV) disease. Routine drug susceptibility testing should be considered in all TB-HIV co-infected patients, and absence of INH resistance should be confirmed phenotypically if genotypic RMR-TB is detected. C1 [Mukinda, F. K.] Univ Stellenbosch, Fac Hlth Sci, Dept Interdisciplinary Hlth Sci, Cape Town, South Africa. [Theron, D.; Roscher, M.] Brewelskloof Hosp, Worcester, MA USA. [van der Spuy, G. D.; Streicher, E. M.; Victor, T. C.; Warren, R. M.] Univ Stellenbosch, Ctr Mol & Cellular Biol, Cape Town, South Africa. [van der Spuy, G. D.; Streicher, E. M.; Victor, T. C.; Warren, R. M.] S African Med Res Council MRC, Cape Town, South Africa. [Jacobson, K. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Musekiwa, A.] S African MRC, Biostat Unit, Cape Town, South Africa. [Coetzee, G. J.] Natl Hlth Lab Serv, Cape Town, South Africa. [Marais, B. J.; Schaaf, H. S.] Univ Stellenbosch, Fac Hlth Sci, Dept Paediat & Child Hlth, ZA-7505 Tygerberg, South Africa. [Marais, B. J.; Schaaf, H. S.] Univ Stellenbosch, Fac Hlth Sci, Desmond Tutu TB Ctr, ZA-7505 Tygerberg, South Africa. [Nachega, J. B.] Univ Stellenbosch, Fac Hlth Sci, Dept Med, ZA-7505 Tygerberg, South Africa. [Nachega, J. B.] Univ Stellenbosch, Fac Hlth Sci, Ctr Infect Dis, ZA-7505 Tygerberg, South Africa. [Nachega, J. B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Nachega, J. B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. RP Mukinda, FK (reprint author), Univ Stellenbosch, Fac Hlth Sci, Dept Interdisciplinary Hlth Sci, Div Community Hlth Sci, POB 19063, ZA-7505 Tygerberg, South Africa. EM fidelekmukinda@gmail.com; hss@sun.ac.za RI Mukinda, Fidele K./I-6012-2012; OI Streicher, Elizabeth/0000-0003-3901-1981; Jacobson, Karen/0000-0003-4239-3685 FU Harry Crossley Fund FX The authors are grateful to the Western Cape Department of Health, Sister Joyce and Sister Jacobs from the MDR-TB office at Brewelskloof Hospital, and J Harvey for statistical advice. Financial support was received from the Harry Crossley Fund. This article is in partial fulfilment of an MScMedSc in Clinical Epidemiology. NR 32 TC 30 Z9 32 U1 0 U2 3 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD FEB PY 2012 VL 16 IS 2 BP 196 EP 202 DI 10.5588/ijtld.11.0116 PG 7 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 883WQ UT WOS:000299666000011 PM 22236920 ER PT J AU Slover, JD Rubash, HE Malchau, H Bosco, JA AF Slover, James D. Rubash, Harry E. Malchau, Henrik Bosco, Joseph A. TI Cost-Effectiveness Analysis of Custom Total Knee Cutting Blocks SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total knee arthroplasty; custom cutting blocks; cost-effectiveness ID ARTHROPLASTY; REPLACEMENT; NAVIGATION AB The purposes of this study were to examine the cost-effectiveness of this technology and to determine improvements in patient outcome needed to make custom total knee cutting blocks cost-effective. A Markov decision model was used to evaluate the cost-effectiveness of custom cutting blocks compared with traditional instrumentation in total knee arthroplasty. The analysis demonstrates routine use of custom cutting blocks for total knee arthroplasty will not be cost-effective unless it results in a significantly reduced revision rate. The reduction necessary increases with increasing costs for the custom blocks. Further research will be necessary to determine if this can be achieved using custom cutting blocks. Patients, surgeons, payers, and institutions should consider this when determining their support of this technology in the absence of supportive data. C1 [Slover, James D.; Bosco, Joseph A.] NYU Hosp Joint Dis, Dept Orthopaed Surg, New York, NY 10003 USA. [Rubash, Harry E.; Malchau, Henrik] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Slover, JD (reprint author), NYU Hosp Joint Dis, Dept Orthopaed Surg, 301 E 17th St,Suite 1616, New York, NY 10003 USA. NR 20 TC 35 Z9 35 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD FEB PY 2012 VL 27 IS 2 BP 180 EP 185 DI 10.1016/j.arth.2011.04.023 PG 6 WC Orthopedics SC Orthopedics GA 882YV UT WOS:000299600700004 PM 21676584 ER PT J AU Park, J Zhang, J Qiu, JH Zhu, XX Degterev, A Lo, EH Whalen, MJ AF Park, Juyeon Zhang, Jimmy Qiu, Jianhua Zhu, Xiaoxia Degterev, Alexei Lo, Eng H. Whalen, Michael J. TI Combination therapy targeting Akt and mammalian target of rapamycin improves functional outcome after controlled cortical impact in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE Akt; cognition; mammalian target of rapamycin; mice; protein kinase B; traumatic brain injury ID TRAUMATIC BRAIN-INJURY; FOCAL CEREBRAL-ISCHEMIA; NEURONAL SURVIVAL; ACTIVATION; KINASE; RATS; PHOSPHORYLATION; APOPTOSIS; CELLS; HISTOPATHOLOGY AB Akt and mammalian target of rapamycin (mTOR) are both activated after traumatic brain injury (TBI), however complex interplay between the two hampers deciphering their functional implications in vivo. We examined the effects of single and combination inhibitors of Akt/mTOR in a mouse controlled cortical impact (CCI) model. Following CCI, phospho-Akt-473 (p-Akt) and -S6 ribosomal protein (p-S6RP), a downstream substrate of mTOR, were increased in cortical and hippocampal brain homogenates (P<0.05 versus sham). At 24 hours, p-S6RP was detected in neurons and was robustly induced in microglia and astrocytes in injured hippocampus. In vivo activity of Akt and mTOR inhibitors administered separately was confirmed by reduced expression of p-GSK3 beta (P<0.01) or p-S6RP (P<0.05), respectively, after CCI. Importantly, administration of Akt and mTOR inhibitors together (but not of either alone) improved postinjury motor (P=0.02) and cognitive deficits (hidden platform trials, P=0.001; probe trials, P<0.05), decreased propidium iodide-positive cells in CA1 and CA3 (P<0.005), and unexpectedly increased p-GSK3 beta in hippocampus. Although the roles of Akt and mTOR in the pathogenesis of TBI remain to be fully elucidated, dual inhibition of Akt and mTOR may have therapeutic potential for TBI. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 330-340; doi:10.1038/jcbfm.2011.131; published online 21 September 2011 C1 [Park, Juyeon; Zhang, Jimmy; Qiu, Jianhua; Zhu, Xiaoxia; Lo, Eng H.; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept PediatNeurosci Ctr, Charlestown, MA 02129 USA. [Zhu, Xiaoxia] Fudan Univ, Huashan Hosp, Dept Rheumatol, Shanghai 200433, Peoples R China. [Degterev, Alexei] Tufts Univ, Dept Biochem, Boston, MA 02111 USA. [Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Whalen, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept PediatNeurosci Ctr, Charlestown, MA 02129 USA. EM mwhalen@partners.org FU NINDS [5RO1NS047447, 5RO1NS064545] FX This work was supported by grants from NINDS 5RO1NS047447 and 5RO1NS064545 (MJW). NR 40 TC 35 Z9 37 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 2012 VL 32 IS 2 BP 330 EP 340 DI 10.1038/jcbfm.2011.131 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 886LZ UT WOS:000299857200013 PM 21934697 ER PT J AU Yuzawa, I Sakadzic, S Srinivasan, VJ Shin, HK Eikermann-Haerter, K Boas, DA Ayata, C AF Yuzawa, Izumi Sakadzic, Sava Srinivasan, Vivek J. Shin, Hwa Kyoung Eikermann-Haerter, Katharina Boas, David A. Ayata, Cenk TI Cortical spreading depression impairs oxygen delivery and metabolism in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral metabolic rate of oxygen; laser speckle flowmetry; mouse; multispectral reflectance imaging; spreading depression ID FUNCTIONAL ACTIVATION; CEREBRAL-CORTEX; BLOOD-FLOW; PARTIAL-PRESSURE; MOUSE CORTEX; REDOX STATE; IN-VIVO; BRAIN; NADH; RAT AB Cortical spreading depression (CSD) is associated with severe hypoperfusion in mice. Using minimally invasive multimodal optical imaging, we show that severe flow reductions during and after spreading depression are associated with a steep decline in cerebral metabolic rate of oxygen. Concurrent severe hemoglobin desaturation suggests that the oxygen metabolism becomes at least in part supply limited, and the decrease in cortical blood volume implicates vasoconstriction as the mechanism. In support of oxygen supply-demand mismatch, cortical nicotinamide adenine dinucleotide (NADH) fluorescence increases during spreading depression for at least 5 minutes, particularly away from parenchymal arterioles. However, modeling of tissue oxygen delivery shows that cerebral metabolic rate of oxygen drops more than predicted by a purely supply-limited model, raising the possibility of a concurrent reduction in oxygen demand during spreading depression. Importantly, a subsequent spreading depression triggered within 15 minutes evokes a monophasic flow increase superimposed on the oligemic baseline, which markedly differs from the response to the preceding spreading depression triggered in naive cortex. Altogether, these data suggest that CSD is associated with long-lasting oxygen supply-demand mismatch linked to severe vasoconstriction in mice. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 376-386; doi:10.1038/jcbfm.2011.148; published online 19 October 2011 C1 [Yuzawa, Izumi; Shin, Hwa Kyoung; Eikermann-Haerter, Katharina; Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Neurovascular Res Lab, Dept Radiol,Sch Med, Charlestown, MA 02129 USA. [Sakadzic, Sava; Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Dept Radiol,Opt Div, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Stroke Serv & Neurosci Intens Care Unit, Dept Neurol,Sch Med, Charlestown, MA 02129 USA. RP Ayata, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Neurovascular Res Lab, Dept Radiol,Sch Med, 149 13th St,Room 6408, Charlestown, MA 02129 USA. EM cayata@partners.org FU National Institutes of Health [NS061505, NS055104, NS057476, K99NS067050]; American Heart Association [10SDG2610275, 11IRG5440002] FX This study was supported by the National Institutes of Health (NS061505, Ayata; NS055104, Lo; NS057476, Boas; K99NS067050, Srinivasan) and the American Heart Association (10SDG2610275, Eikermann-Haerter; 11IRG5440002, Srinivasan). NR 42 TC 21 Z9 21 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 2012 VL 32 IS 2 BP 376 EP 386 DI 10.1038/jcbfm.2011.148 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 886LZ UT WOS:000299857200017 PM 22008729 ER PT J AU Elvington, A Atkinson, C Kulik, L Zhu, H Yu, J Kindy, MS Holers, VM Tomlinson, S AF Elvington, Andrew Atkinson, Carl Kulik, Liudmila Zhu, Hong Yu, Jin Kindy, Mark S. Holers, V. Michael Tomlinson, Stephen TI Pathogenic Natural Antibodies Propagate Cerebral Injury Following Ischemic Stroke in Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MANNOSE-BINDING LECTIN; ANNEXIN-IV EXPRESSION; REPERFUSION INJURY; SKELETAL-MUSCLE; ISCHEMIA/REPERFUSION INJURY; APOPTOTIC CELLS; COMPLEMENT; IGM; PHOSPHORYLCHOLINE; PROTECTION AB Self-reactive natural Abs initiate injury following ischemia and reperfusion of certain tissues, but their role in ischemic stroke is unknown. We investigated neoepitope expression in the postischemic brain and the role of natural Abs in recognizing these epitopes and mediating complement-dependent injury. A novel IgM mAb recognizing a subset of phospholipids (C2) and a previously characterized anti-annexin IV mAb (B4) were used to reconstitute and characterize injury in Ab-deficient Rag1(-/-) mice after 60 min of middle cerebral artery occlusion and reperfusion. Reconstitution with C2 or B4 mAb in otherwise protected Rag1(-/-) mice restored injury to that seen in wild-type (wt) mice, as demonstrated by infarct volume, demyelination, and neurologic scoring. IgM deposition was demonstrated in both wt mice and reconstituted Rag1(-/-) mice, and IgM colocalized with the complement activation fragment C3d following B4 mAb reconstitution. Further, recombinant annexin IV significantly reduced infarct volumes in wt mice and in Rag1(-/-) mice administered normal mouse serum, demonstrating that a single Ab reactivity is sufficient to develop cerebral ischemia reperfusion injury in the context of an entire natural Ab repertoire. Finally, C2 and B4 mAbs bound to hypoxic, but not normoxic, human endothelial cells in vitro. Thus, the binding of pathogenic natural IgM to postischemic neoepitopes initiates complement-dependent injury following murine cerebral ischemia and reperfusion, and, based also on previous data investigating IgM reactivity in human serum, there appears to be a similar recognition system in both mouse and man. The Journal of Immunology, 2012, 188: 1460-1468. C1 [Elvington, Andrew; Atkinson, Carl; Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29401 USA. [Kulik, Liudmila; Holers, V. Michael] Univ Colorado Denver, Dept Med & Immunol, Aurora, CO 80045 USA. [Zhu, Hong; Yu, Jin; Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Neurosci Inst, Charleston, SC 29425 USA. [Kindy, Mark S.; Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave,BSB 201, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU National Institutes of Health [HL082485, HL86576, AI31105]; Department of Veterans Affairs [NURC-001218A, NURC-051010F] FX This work was supported by grants from the National Institutes of Health (HL082485, HL86576, and AI31105) and the Department of Veterans Affairs (Merit Awards NURC-001218A and NURC-051010F). NR 47 TC 21 Z9 21 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 FEB 1 PY 2012 VL 188 IS 3 BP 1460 EP 1468 DI 10.4049/jimmunol.1102132 PG 9 WC Immunology SC Immunology GA 884FL UT WOS:000299690200061 PM 22198950 ER PT J AU Ji, ZY Njauw, CN Taylor, M Neel, V Flaherty, KT Tsao, HS AF Ji, Zhenyu Njauw, Ching Ni Taylor, Michael Neel, Victor Flaherty, Keith T. Tsao, Hensin TI p53 Rescue through HDM2 Antagonism Suppresses Melanoma Growth and Potentiates MEK Inhibition SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID HUMAN-MALIGNANT MELANOMA; AZD6244 ARRY-142886; TUMOR SUPPRESSION; CELL-LINE; MDM2; MUTATIONS; GENE; APOPTOSIS; PATHWAY; CANCER AB Oncogenesis reflects an orchestrated interaction between misguided growth signals. Although much effort has been launched to pharmacologically disable activated oncogenes, one sidelined approach is the restoration of tumor suppressive signals. As TP53 is often structurally preserved, but functionally crippled, by CDKN2A/ARF loss in melanoma, rescue of p53 function represents an attractive point of vulnerability in melanoma. In this study, we showed that both p53 protein and activity levels in melanoma cells were strongly induced by nutlin-3, a canonical HDM2 antagonist. Among a test panel of 51 cell lines, there was a marked reduction in melanoma viability that was directly linked to TP53 status. Moreover, we also found that the melanoma growth suppression mediated by mitogen-activated protein kinase/extracellular signal-regulated kinase inhibition was potentiated by HDM2 antagonism. These results provide fundamental insights into the intact p53 circuitry, which can be restored through small molecule inhibitors and potentially deployed for therapeutic gain. C1 [Ji, Zhenyu; Njauw, Ching Ni; Taylor, Michael; Neel, Victor; Tsao, Hensin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Flaherty, Keith T.; Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. [Ji, Zhenyu; Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Tsao, HS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org FU American Skin Association; Cephalon FX This work was supported in part by a Howard Millstein Innovation Award from the American Skin Association (to HT) and by generous donors to the MGH Millennium Melanoma Fund on behalf of melanoma research.; KTF has been a consultant at Roche/Genentech and GlaxoSmithKline. HT has been a consultant for Genentech, SciBASE, and Quest, and has received research funding from Cephalon. However, none of the research presented in this article represents a conflict with the entities disclosed. NR 35 TC 33 Z9 33 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2012 VL 132 IS 2 BP 356 EP 364 DI 10.1038/jid.2011.313 PG 9 WC Dermatology SC Dermatology GA 877XH UT WOS:000299215500016 PM 21993556 ER PT J AU Cedeno-Laurent, F Opperman, MJ Barthel, SR Hays, D Schatton, T Zhan, Q He, XY Matta, KL Supko, JG Frank, MH Murphy, GF Dimitroff, CJ AF Cedeno-Laurent, Filiberto Opperman, Matthew J. Barthel, Steven R. Hays, Danielle Schatton, Tobias Zhan, Qian He, Xiaoying Matta, Khushi L. Supko, Jeffrey G. Frank, Markus H. Murphy, George F. Dimitroff, Charles J. TI Metabolic Inhibition of Galectin-1-Binding Carbohydrates Accentuates Antitumor Immunity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID LYMPHOCYTE-ASSOCIATED ANTIGEN; SKIN-HOMING RECEPTORS; T-CELLS; P-SELECTIN; DIFFERENTIAL GLYCOSYLATION; DENDRITIC CELLS; BREAST-CANCER; INFLAMED SKIN; EXPRESSION; ADHESION AB Galectin-1 (Gal-1) has been shown to play a major role in tumor immune escape by inducing apoptosis of effector leukocytes and correlating with tumor aggressiveness and disease progression. Thus, targeting the Gal-1/Gal-1 ligand axis represents a promising cancer therapeutic approach. Here, to test the Gal-1-mediated tumor immune evasion hypothesis and demonstrate the importance of Gal-1-binding N-acetyllactosamines in controlling the fate and function of antitumor immune cells, we treated melanoma-or lymphoma-bearing mice with peracetylated 4-fluoro-glucosamine (4-F-GlcNAc), a metabolic inhibitor of N-acetyllactosamine biosynthesis, and analyzed tumor growth and immune profiles. We found that 4-F-GlcNAc spared Gal-1-mediated apoptosis of T cells and natural killer (NK) cells by decreasing their expression of Gal-1-binding determinants. 4-F-GlcNAc enhanced tumor lymphocytic infiltration and promoted elevations in tumor-specific cytotoxic T cells and IFN-gamma levels, while lowering IL-10 production. Collectively, our data suggest that metabolic lowering of Gal-1-binding N-acetyllactosamines may attenuate tumor growth by boosting antitumor immune cell levels, representing a promising approach for cancer immunotherapy. C1 [Dimitroff, Charles J.] Brigham & Womens Hosp, HIM, Dept Dermatol, Boston, MA 02115 USA. [Cedeno-Laurent, Filiberto; Barthel, Steven R.; He, Xiaoying; Supko, Jeffrey G.; Murphy, George F.; Dimitroff, Charles J.] Harvard Univ, Sch Med, Boston, MA USA. [Schatton, Tobias; Frank, Markus H.] Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Zhan, Qian; Murphy, George F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [He, Xiaoying; Supko, Jeffrey G.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Matta, Khushi L.] Roswell Pk Canc Inst, Dept Canc Biol, Buffalo, NY 14263 USA. RP Dimitroff, CJ (reprint author), Brigham & Womens Hosp, HIM, Dept Dermatol, Room 662,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cdimitroff@rics.bwh.harvard.edu RI Frank, Markus/O-1625-2014; OI Frank, Markus/0000-0002-1312-0488; Murphy, George/0000-0003-3464-793X FU NIH/NCI [CA118124]; NIH/NCCAM [AT004268] FX FC-L designed the research, performed the experiments, analyzed the data, and wrote the paper; MO designed the research, performed the experiments, and analyzed the data; SRB designed the research, performed the experiments, and analyzed the data; DH performed the experiments and analyzed the data; KLM provided reagents; JGS performed the experiments and analyzed the data; XH performed the experiments and analyzed the data; MHF performed the experiments and analyzed the data; GFM performed the experiments and analyzed the data; TS performed the experiments and analyzed the data; QZ performed the experiments and analyzed the data; CJD conceived the study, designed the research, analyzed the data, wrote the paper, and supervised all experimentation. This work was supported by NIH/NCI RO1 grant CA118124 to CJ Dimitroff and NIH/NCCAM RO1 grant AT004268 to CJ Dimitroff. NR 43 TC 24 Z9 26 U1 0 U2 8 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 FEB PY 2012 VL 132 IS 2 BP 410 EP 420 DI 10.1038/jid.2011.335 PG 11 WC Dermatology SC Dermatology GA 877XH UT WOS:000299215500022 PM 22158550 ER PT J AU Zoghbi, GJ Iskandrian, AE AF Zoghbi, Gilbert J. Iskandrian, Ami E. TI Selective adenosine agonists and myocardial perfusion imaging SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Myocardial perfusion imaging; selective adenosine agonists; regadenoson; binodenoson; apadenoson ID A(2A) RECEPTOR AGONIST; INITIAL CLINICAL-EXPERIENCE; PLACEBO-CONTROLLED TRIAL; BLOOD-FLOW-VELOCITY; HEART-RATE RESPONSE; PHARMACOLOGICAL STRESS; CORONARY VASODILATION; CONSCIOUS DOGS; DOUBLE-BLIND; REGADENOSON AB Selective adenosine receptor agonists have several advantages for use as stress agents in conjunction with myocardial perfusion imaging compared to the non selective agents such as adenosine and dipyridamole. This review will summarize the pre-clinical and clinical data on the selective adenosine agonist stress agents regadenoson (Lexiscan(A (R))), binodenoson (CorVue (TM)) and apadenoson (Stedivaze (TM)) that have been studied so far with focus on regadenoson that has the most clinical data published so far. The article will review the adenosine receptor types and properties. It will also review the various attributes of the selective adenosine agonists including their pharmacology, pharmacokinetics and pharmacodynamics, their coronary vasodilatory and hemodynamic effects, their safety and side effects, their interactions with other drugs and their use with myocardial perfusion imaging. The landmark trials of the selective adenosine agonists will be reviewed as well as their use in special patient populations undergoing stress myocardial perfusion imaging. C1 [Zoghbi, Gilbert J.; Iskandrian, Ami E.] Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Zoghbi, Gilbert J.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Zoghbi, GJ (reprint author), Univ Alabama, Div Cardiovasc Dis, FOT 920,1960 6th Ave S, Birmingham, AL 35294 USA. EM gzoghbi@uab.edu NR 42 TC 25 Z9 25 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD FEB PY 2012 VL 19 IS 1 BP 126 EP 141 DI 10.1007/s12350-011-9474-9 PG 16 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 881XC UT WOS:000299524100017 PM 22130964 ER PT J AU Olfson, M Huang, C Gerhard, T Winterstein, AG Crystal, S Allison, PD Marcus, SC AF Olfson, Mark Huang, Cecilia Gerhard, Tobias Winterstein, Almut G. Crystal, Stephen Allison, Paul D. Marcus, Steven C. TI Stimulants and Cardiovascular Events in Youth With Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; stimulants; cardiovascular events; drug safety; pharmacoepidemiology ID DEFICIT-HYPERACTIVITY DISORDER; ACUTE MYOCARDIAL-INFARCTION; TACHYCARDIA-INDUCED CARDIOMYOPATHY; POSITIVE PREDICTIVE-VALUE; BLOOD-PRESSURE; CHILDREN; DISEASE; ADHD; ADOLESCENTS; STROKE AB Objective: This study examined associations between stimulant use and risk of cardiovascular events and symptoms in youth with attention-deficit/hyperactivity disorder and compared the risks associated with methylphenidate and amphetamines. Method: Claims were reviewed of privately insured young people 6 to 21 years old without known cardiovascular risk factors (n = 171,126). A day-level cohort analysis evaluated the risk of cardiovascular events after a diagnosis of attention-deficit/hyperactivity disorder in relation to stimulant exposures. Based on filled stimulant prescriptions, follow-up days were classified as current, past, and no stimulant use. Endpoints included an emergency department or inpatient diagnosis of angina pectoris, cardiac dysrhythmia, or transient cerebral ischemia (cardiac events) or tachycardia, palpitations, or syncope (cardiac symptoms). Results: There were 0.92 new cardiac events and 3.08 new cardiac symptoms per 1,000,000 days of current stimulant use. Compared with no stimulant use (reference group), the adjusted odds ratios of cardiac events were 0.69 (95% confidence interval 0.42-1.12) during current stimulant use and 1.18 (95% CI 0.83-1.66) during past stimulant use. The corresponding adjusted odds ratios for cardiac symptoms were 1.18 (95% CI 0.89-1.59) for current and 0.93 (95% CI 0.71-1.21) for past stimulant use. No significant differences were observed in risks of cardiovascular events (2.14, 95% CI 0.82-5.63) or symptoms (1.08, 95% CI 0.66-1.79) for current methylphenidate use compared with amphetamine use (reference group). Conclusions: Clinical diagnoses of cardiovascular events and symptoms were rare and not associated with stimulant use. The results help to allay concerns over the cardiovascular safety of stimulant treatment for attention-deficit/hyperactivity disorder in young people without known pre-existing risk factors. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(2):147-156. C1 [Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Olfson, Mark] Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. [Huang, Cecilia; Crystal, Stephen] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ 08855 USA. [Gerhard, Tobias] Rutgers State Univ, Ernest Mario Sch Pharm, Piscataway, NJ 08855 USA. [Winterstein, Almut G.] Univ Florida, Coll Pharm, Gainesville, FL USA. [Winterstein, Almut G.] Univ Florida, Coll Med & Publ Hlth, Gainesville, FL USA. [Winterstein, Almut G.] Univ Florida, Coll Hlth Profess, Gainesville, FL USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. RP Olfson, M (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@columbia.edu RI Allison, Paul/A-1345-2007; winterstein, Almut/A-3017-2014 OI Allison, Paul/0000-0002-0646-5242; winterstein, Almut/0000-0002-6518-5961 FU National Institute of Mental Health [R21 MH079905]; Agency for Healthcare Research and Quality [U18 HS016097]; Center for Education and Research on Mental Health Therapeutics; Eli Lilly and Co.; Bristol-Myers Squibb; Ortho-McNeil Janssen FX This study was supported by National Institute of Mental Health grant R21 MH079905, Agency for Healthcare Research and Quality award U18 HS016097, and the Center for Education and Research on Mental Health Therapeutics.; Dr. Olfson has received research grants to Columbia University from Eli Lilly and Co. and Bristol-Myers Squibb. Dr. Marcus has received grant support from Ortho-McNeil Janssen and has served as a consultant to AstraZeneca. Drs. Huang, Gerhard, Winterstein, Crystal, and Allison report no biomedical financial interests or potential conflicts of interest. NR 61 TC 30 Z9 30 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2012 VL 51 IS 2 BP 147 EP 156 DI 10.1016/j.jaac.2011.11.008 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 882YD UT WOS:000299598900006 PM 22265361 ER PT J AU Scharf, JM Miller, LL Mathews, CA Ben-Shlomo, Y AF Scharf, Jeremiah M. Miller, Laura L. Mathews, Carol A. Ben-Shlomo, Yoav TI Prevalence of Tourette Syndrome and Chronic Tics in the Population-Based Avon Longitudinal Study of Parents and Children Cohort SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE Tourette syndrome; prevalence; ALSPAC; obsessive-compulsive disorder; attention-deficit/hyperactivity disorder ID SCHOOL-AGE-CHILDREN; DISORDERS; PSYCHOPATHOLOGY; SCHOOLCHILDREN; ALSPAC; EPIDEMIOLOGY; COMORBIDITY; SPECTRUM AB Objective: Recent epidemiologic studies have demonstrated that Tourette syndrome (TS) and chronic tic disorder (CT) are more common than previously recognized. However, few population-based studies have examined the prevalence of co-occurring neuropsychiatric conditions such as obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). We evaluated the prevalence of TS, CT, and their overlap with OCD and ADHD in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Method: A total of 6,768 children were evaluated using longitudinal data from mother-completed questionnaires. DSM-IV-TR diagnoses of TS and CT were derived using three levels of diagnostic stringency (Narrow, Intermediate, and Broad). Validity of the case definitions was assessed by comparing gender ratios and rates of co-occurring OCD and ADHD using heterogeneity analyses. Results: Age 13 prevalence rates for TS (0.3% for Narrow; 0.7% for Intermediate) and CT (0.5% for Narrow; 1.1% for Intermediate) were consistent with rates from other population-based studies. Rates of co-occurring OCD and ADHD were higher in TS and CT Narrow and Intermediate groups compared with controls but lower than has been previously reported. Only 8.2% of TS Intermediate cases had both OCD and ADHD; 69% of TS Intermediate cases did not have either co-occurring OCD or ADHD. Conclusions: This study suggests that co-occurring OCD and ADHD is markedly lower in TS cases derived from population-based samples than has been reported in clinically ascertained TS cases. Further examination of the range of co-occurring neuropsychiatric disorders in population-based TS samples may shed new perspective on the underlying shared pathophysiology of these three neurodevelopmental conditions. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(2):192-201. C1 [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Scharf, Jeremiah M.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Miller, Laura L.; Ben-Shlomo, Yoav] Univ Bristol, Sch Social & Community Med, Bristol BS8 1TH, Avon, England. [Mathews, Carol A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Scharf, JM (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM jscharf@partners.org FU Tourette Syndrome Association; Wellcome Trust [092731]; National Institutes of Health (NIH); Center for Disease Control; British Heart Foundation; National Institute for Health Research; Parkinson's Disease Society; Alzheimer's Society; Cancer Research UK; Medical Research Council; Diabetes UK FX This research was specifically funded by a grant from the Tourette Syndrome Association. The UK Medical Research Council and the Wellcome Trust (grant ref: 092731) and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children (ALSPAC).; Dr. Scharf has received research grant funding from the National Institutes of Health (NIH) and from the TSA. He has received honoraria from the TSA and the Center for Disease Control. Dr. Mathews has received research grant funding from the NIH and from TSA. She has served on the TSA Medical Advisory Board. She has received honoraria from the TSA and the Center for Disease Control. Dr. Ben-Shlomo has received grant funding horn the British Heart Foundation, the National Institute for Health Research-Health Technology Assessment program (NIHR-HTA), Parkinson's Disease Society, Diabetes UK, Alzheimer's Society, and Cancer Research UK. Ms. Miller has received grant funding from the Medical Research Council and the Wellcome Trust. NR 33 TC 46 Z9 50 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2012 VL 51 IS 2 BP 192 EP 201 DI 10.1016/j.jaac.2011.11.004 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 882YD UT WOS:000299598900010 PM 22265365 ER PT J AU Bridge, JA Marcus, SC Olfson, M AF Bridge, Jeffrey A. Marcus, Steven C. Olfson, Mark TI Outpatient Care of Young People After Emergency Treatment of Deliberate Self-Harm SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE deliberate self-harm; emergency care; outpatient mental health care; young people; suicide ID MENTAL-HEALTH-SERVICES; ADOLESCENT SUICIDE; INJURY; ATTEMPTERS; ACCIDENT AB Objective: Little is known about the mental health care received by young people after an episode of deliberate self-harm. This study examined predictors of emergency department (ED) discharge, mental health assessments in the ED, and follow-up outpatient mental health care for Medicaid-covered youth with deliberate self-harm. Method: A retrospective longitudinal cohort analysis was conducted of national 2006 Medicaid claims data supplemented with the Area Resource File and a Substance Abuse and Mental Health Services Administration Medicaid policy survey of state policy characteristics focusing on ED treatment episodes by youth 10 to 19 years old for deliberate self-harm (n = 3,241). Rates and adjusted risk ratios (ARR) of discharge to the community, mental health assessments in the ED, and outpatient visits during the 30 days after the ED visit were assessed. Results: Most patients (72.9%) were discharged to the community. Discharge was inversely related to recent psychiatric hospitalization (ARR 0.75, 99% confidence interval [CI] 0.63-0.90). Thirty-nine percent of discharged patients received a mental health assessment in the ED and a roughly similar percentage (43.0%) received follow-up outpatient mental health care. Follow-up mental health care was directly related to recent outpatient (ARR 2.58, 99% CI 2.27-2.94) and inpatient (ARR 1.33, 99% CI 1.14-1.56) mental health care and inversely related to Hispanic ethnicity (ARR 0.78, 99% CI 0.64-0.95) and residence in a county with medium-to-high poverty rates (ARR 0.84, 99% CI 0.73 0.97). Conclusions: A substantial proportion of young Medicaid beneficiaries who present to EDs with deliberate self-harm are discharged to the community and do not receive emergency mental health assessments or follow-up outpatient mental health care. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(2):213-222. C1 [Olfson, Mark] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Bridge, Jeffrey A.] Ohio State Univ, Ctr Innovat Pediat Practice, Nationwide Childrens Hosp, Res Inst, Columbus, OH 43210 USA. [Marcus, Steven C.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Olfson, M (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@columbia.edu FU American Foundation for Suicide Prevention; Eli Lilly and Co.; Bristol-Myers Squibb; Ortho-McNeil Janssen FX This research was funded by a grant to Columbia University from the American Foundation for Suicide Prevention (MO).; Dr. Olfson has received research grants to Columbia University from Eli Lilly and Co. and Bristol-Myers Squibb. Dr. Marcus has received grant support from Ortho-McNeil Janssen and has served as a consultant to AstraZeneca. Dr. Bridge reports no biomedical financial interests or potential conflicts of interest. NR 36 TC 21 Z9 21 U1 3 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2012 VL 51 IS 2 BP 213 EP 222 DI 10.1016/j.jaac.2011.11.002 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 882YD UT WOS:000299598900012 PM 22265367 ER PT J AU Moore, C AF Moore, Cynthia TI The Blessing of a B Minus: Using Jewish Teachings to Raise Resilient Teenagers SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Moore, Cynthia] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Moore, C (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Cmoore8@partners.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2012 VL 51 IS 2 BP 223 EP 225 DI 10.1016/j.jaac.2011.12.005 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 882YD UT WOS:000299598900014 ER PT J AU LaMuraglia, GM Houbballah, R Laposata, M AF LaMuraglia, Glenn M. Houbballah, Rabih Laposata, Michael TI The identification and management of heparin-induced thrombocytopenia in the vascular patient SO JOURNAL OF VASCULAR SURGERY LA English DT Review ID MOLECULAR-WEIGHT HEPARIN; INTERNATIONAL NORMALIZED RATIO; FACTOR 4/HEPARIN ANTIBODIES; LINKED-IMMUNOSORBENT-ASSAY; DIRECT THROMBIN INHIBITOR; VENOUS LIMB GANGRENE; RISK-FACTORS; ARTERIAL RECONSTRUCTION; ANTIPLATELET ANTIBODIES; CARDIOPULMONARY BYPASS AB Heparin-induced thrombocytopenia (HIT) is a serious, acquired, prothrombotic disorder caused by an antibody response to the heparin-platelet factor 4 complex, which can precipitate arterial as well as venous thromboembolic complications. HIT should be suspected in patients exposed to heparin who present with an unexplained thrombosis or a significant drop in platelet count, or both. Once HIT is suspected or identified, there are specific approaches to its diagnosis and management, with emphasis on removal of all heparin compounds and administration of alternative nonheparin anticoagulants. Generally, HIT is a self-limiting syndrome that resolves when the antibody titers disappear. Patients should be anticoagulated for up to 6 months, depending on the clinical scenario; however, the management of patients with remote or recent HIT requiring a vascular procedure requires special considerations. (J Vase Surg 2012;55: 562-70.) C1 [LaMuraglia, Glenn M.; Houbballah, Rabih] Harvard Univ, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Gen Surg Serv,Sch Med, Boston, MA 02114 USA. [Laposata, Michael] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Gen Surg Serv,Sch Med, ACC440,15 Parkman St, Boston, MA 02114 USA. FU Monte and Rita Goldman Foundation; John F. Murphy and the Bay State Federal Savings Foundation FX Supported in part by the Monte and Rita Goldman Foundation and John F. Murphy and the Bay State Federal Savings Foundation. NR 94 TC 4 Z9 6 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2012 VL 55 IS 2 BP 562 EP 570 DI 10.1016/j.jvs.2011.10.082 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 880YN UT WOS:000299446600039 PM 22188737 ER PT J AU Glaser, JD Bensley, RP Hurks, R Pomposelli, F Hamdan, A Wyers, M Chaikof, E Schermerhorn, ML AF Glaser, Julia D. Bensley, Rodney P. Hurks, Rob Pomposelli, Frank Hamdan, Allen Wyers, Mark Chaikof, Elliot Schermerhorn, Marc L. TI Fate of the Contralateral Limb in Lower Extremity Amputation SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract C1 [Glaser, Julia D.; Bensley, Rodney P.; Hurks, Rob; Pomposelli, Frank; Hamdan, Allen; Wyers, Mark; Chaikof, Elliot; Schermerhorn, Marc L.] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2012 VL 55 IS 2 BP 620 EP 620 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 880YN UT WOS:000299446600052 ER PT J AU Covington, MD Schnellmann, RG AF Covington, Marisa D. Schnellmann, Rick G. TI Chronic high glucose downregulates mitochondrial calpain 10 and contributes to renal cell death and diabetes-induced renal injury SO KIDNEY INTERNATIONAL LA English DT Article DE acute kidney injury; apoptosis; diabetic nephropathy; hyperglycemia; mitochondria ID INSULIN-SECRETION; KIDNEY; NEPHROPATHY; EXPRESSION; APOPTOSIS; SIRNA; RAT; TRANSLOCATION; ACTIVATION; CULTURE AB Whereas most calpains are cytosolic proteases, calpain 10 is resident in mitochondria and is important in mitochondria! homeostasis. Because calpain 10 has been implicated in type 2 diabetes, we studied its possible role in diabetes-induced renal dysfunction. We treated renal proximal tubular cells with high glucose (17 mmol/l) and found decreased mitochondrial calpain 10 mRNA and protein at 96h compared with cells incubated with 0 or 5 mmol/l glucose or 17 mmol/l D-mannitol. High glucose increased mitochondrial calpain 10 substrates (NDUFB8 and ATP synthase p), decreased basal and uncoupled respiration, and initiated cell apoptosis as indicated by cleaved caspase 3 and nuclear condensation. Renal calpain 10 protein and mRNA were specifically decreased in streptozotocin-induced diabetic rats with kidney dysfunction, and in diabetic ob/ob mice. In agreement with our in vitro data, the kidneys of streptozotocin-induced diabetic rats had elevated calpain 10 substrates and cleaved caspase 3. Finally, specific siRNA-induced knockdown of calpain 10 in the proximal tubules of control rats resulted in decreased renal function as evidenced by increased serum creatinine, and increased caspase 3 cleavage compared with rats receiving scrambled siRNA. Thus, the glucose-induced loss of calpain 10 in vivo results in renal cell apoptosis and organ failure through accumulation of mitochondrial calpain 10 substrates and mitochondrial dysfunction. Whether this is a major cause of the decreased renal function in diabetic nephropathy will require further studies. Kidney International (2012) 81, 391-400; doi:10.1038/ki.2011.356; published online 19 October 2011 C1 [Covington, Marisa D.; Schnellmann, Rick G.] Med Univ S Carolina, Ctr Cell Death Injury & Regenerat, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Ctr Cell Death Injury & Regenerat, Dept Pharmaceut & Biomed Sci, 280 Calhoun St,POB 250140, Charleston, SC 29425 USA. EM schnell@musc.edu FU NIEHS [ES-012239]; NIGMS [GM-084147]; Biomedical Laboratory of the Department of Veterans Affairs; National Institutes of Health [T32 HL007260, C06 RR-015455] FX This research was supported by NIEHS grant ES-012239 (to RGS) and NIGMS grant GM-084147 (to RGS), and by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. MDC was supported by the National Institutes of Health Training grant T32 HL007260. Animal facilities were funded by NIH grant C06 RR-015455. NR 35 TC 20 Z9 24 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2012 VL 81 IS 4 BP 391 EP 400 DI 10.1038/ki.2011.356 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 886JJ UT WOS:000299850400009 PM 22012129 ER PT J AU Kuo, DZ Houtrow, AJ Arango, P Kuhlthau, KA Simmons, JM Neff, JM AF Kuo, Dennis Z. Houtrow, Amy J. Arango, Polly Kuhlthau, Karen A. Simmons, Jeffrey M. Neff, John M. TI Family-Centered Care: Current Applications and Future Directions in Pediatric Health Care SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Editorial Material DE Family-centered care; Family-centered rounds; Patient-centered care ID BEDSIDE CASE PRESENTATIONS; EMERGENCY-DEPARTMENT UTILIZATION; MEDICAL HOME; YOUNG-CHILDREN; ROUNDS; PATIENT; NEEDS; COORDINATION; CONTINUITY; PARENTS AB Family-centered care (FCC) is a partnership approach to health care decision-making between the family and health care provider. FCC is considered the standard of pediatric health care by many clinical practices, hospitals, and health care groups. Despite widespread endorsement, FCC continues to be insufficiently implemented into clinical practice. In this paper we enumerate the core principles of FCC in pediatric health care, describe recent advances applying FCC principles to clinical practice, and propose an agenda for practitioners, hospitals, and health care groups to translate FCC into improved health outcomes, health care delivery, and health care system transformation. C1 [Kuo, Dennis Z.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Kuo, Dennis Z.] Univ Arkansas Med Sci, Ctr Appl Res & Evaluat, Dept Pediat, Little Rock, AR 72205 USA. [Houtrow, Amy J.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Arango, Polly] Family Voices, Algodones, NM USA. [Kuhlthau, Karen A.] MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. [Kuhlthau, Karen A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Simmons, Jeffrey M.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Neff, John M.] Seattle Childrens Hosp, Seattle, WA USA. [Neff, John M.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. RP Kuo, DZ (reprint author), Arkansas Childrens Hosp, Pediat CARE Slot 512-26,1 Childrens Way, Little Rock, AR 72202 USA. EM dzkuo@uams.edu FU NCRR NIH HHS [KL2RR029883, KL2 RR029883]; PHS HHS [K12 2K12H001097-11] NR 89 TC 89 Z9 94 U1 3 U2 18 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD FEB PY 2012 VL 16 IS 2 BP 297 EP 305 DI 10.1007/s10995-011-0751-7 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 879YJ UT WOS:000299370400003 PM 21318293 ER PT J AU Gordon, CM Mantzoros, CS AF Gordon, Catherine M. Mantzoros, Christos S. TI Dietary calcium and body weight: what's the "skinny"? SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID RECEPTOR GENE POLYMORPHISMS; VITAMIN-D DEFICIENCY; PARATHYROID-HORMONE; INSULIN-SECRETION; CONTROLLED-TRIAL; MORBID-OBESITY; S100 PROTEINS; LEPTIN; WOMEN; METABOLISM C1 [Gordon, Catherine M.] Childrens Hosp Boston, Div Adolescent Med, Bone Hlth Program, Boston, MA USA. [Gordon, Catherine M.] Childrens Hosp Boston, Div Endocrinol, Bone Hlth Program, Boston, MA USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA 02130 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Dept Med, Div Endocrinol Diabet & Metab,Beth Israel Deacone, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. RP Gordon, CM (reprint author), Childrens Hosp Boston, Div Adolescent Med, Bone Hlth Program, 300 Longwood Ave, Boston, MA USA. EM catherine.gordon@childrens.harvard.edu NR 39 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD FEB PY 2012 VL 61 IS 2 BP 137 EP 139 DI 10.1016/j.metabol.2011.11.007 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 885CX UT WOS:000299757200001 PM 22269212 ER PT J AU Cetrulo, CL Barone, AAL Jordan, K Chang, DS Louie, K Buntic, RF Brooks, D AF Cetrulo, Curtis L., Jr. Barone, Angelo A. Leto Jordan, Kathleen Chang, David S. Louie, Kevin Buntic, Rudolf F. Brooks, Darrell TI A multi-disciplinary approach to the management of fungal osteomyelitis: Current concepts in post-traumatic lower extremity reconstruction: A case report SO MICROSURGERY LA English DT Article ID SOFT-TISSUE FLAP; SCEDOSPORIUM-INFLATUM; MUSCLE FLAP; INFECTION; OXYGEN AB Limb salvage in fungal osteomyelitis of the post-traumatic lower extremity represents a difficult clinical problem requiring aggressive management. We report lower extremity salvage by radical bony debridement, free tissue transfer, distraction osteogenesis with bone-docking, and a novel antifungal regimen in a clinical setting of infection with Scedosporium inflatum, historically requiring amputation in 100% of cases. We treated Scedosporium inflatum osteomyelitis of the tibia and calcaneus with radical debridement of infected bone, free partial medial rectus abdominis muscle flap coverage, transport distraction osteogenesis, and combination voriconazole/terbinafine chemotherapy, a novel antifungal regimen. We achieved successful control of the infection, limb salvage, and an excellent functional outcome through aggressive debridement of infected bone and soft tissue, elimination of dead space within the bony defect, the robust perfusion provided by the free flap, the hypervascular state induced by distraction osteogenesis, and the synergism of the novel antifungal regimen. (C) 2011 Wiley Periodicals, Inc. Microsurgery, 2012. C1 [Cetrulo, Curtis L., Jr.; Barone, Angelo A. Leto; Jordan, Kathleen; Chang, David S.; Louie, Kevin; Buntic, Rudolf F.; Brooks, Darrell] Harvard Univ, Sch Med, Div Plast & Reconstruct Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cetrulo, CL (reprint author), Harvard Univ, Sch Med, Div Plast & Reconstruct Surg, Massachusetts Gen Hosp, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM ccetrulo@partners.org NR 18 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0738-1085 J9 MICROSURG JI Microsurgery PD FEB PY 2012 VL 32 IS 2 BP 144 EP 147 DI 10.1002/micr.20956 PG 4 WC Surgery SC Surgery GA 883JE UT WOS:000299629400008 PM 22389900 ER PT J AU Kirov, G Pocklington, AJ Holmans, P Ivanov, D Ikeda, M Ruderfer, D Moran, J Chambert, K Toncheva, D Georgieva, L Grozeva, D Fjodorova, M Wollerton, R Rees, E Nikolov, I van de Lagemaat, LN Bayes, A Fernandez, E Olason, PI Bottcher, Y Komiyama, NH Collins, MO Choudhary, J Stefansson, K Stefansson, H Grant, SGN Purcell, S Sklar, P O'Donovan, MC Owen, MJ AF Kirov, G. Pocklington, A. J. Holmans, P. Ivanov, D. Ikeda, M. Ruderfer, D. Moran, J. Chambert, K. Toncheva, D. Georgieva, L. Grozeva, D. Fjodorova, M. Wollerton, R. Rees, E. Nikolov, I. van de Lagemaat, L. N. Bayes, A. Fernandez, E. Olason, P. I. Boettcher, Y. Komiyama, N. H. Collins, M. O. Choudhary, J. Stefansson, K. Stefansson, H. Grant, S. G. N. Purcell, S. Sklar, P. O'Donovan, M. C. Owen, M. J. TI De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE CNV; de novo; DLG; EHMT1; postsynaptic; schizophrenia ID COPY NUMBER VARIATION; RARE CHROMOSOMAL DELETIONS; MENTAL-RETARDATION; GENOME-WIDE; HIGH-RISK; VARIANTS; AUTISM; GENES; MICRODELETIONS; DUPLICATIONS AB A small number of rare, recurrent genomic copy number variants (CNVs) are known to substantially increase susceptibility to schizophrenia. As a consequence of the low fecundity in people with schizophrenia and other neurodevelopmental phenotypes to which these CNVs contribute, CNVs with large effects on risk are likely to be rapidly removed from the population by natural selection. Accordingly, such CNVs must frequently occur as recurrent de novo mutations. In a sample of 662 schizophrenia proband-parent trios, we found that rare de novo CNV mutations were significantly more frequent in cases (5.1% all cases, 5.5% family history negative) compared with 2.2% among 2623 controls, confirming the involvement of de novo CNVs in the pathogenesis of schizophrenia. Eight de novo CNVs occurred at four known schizophrenia loci (3q29, 15q11.2, 15q13.3 and 16p11.2). De novo CNVs of known pathogenic significance in other genomic disorders were also observed, including deletion at the TAR (thrombocytopenia absent radius) region on 1q21.1 and duplication at the WBS (Williams-Beuren syndrome) region at 7q11.23. Multiple de novos spanned genes encoding members of the DLG (discs large) family of membrane-associated guanylate kinases (MAGUKs) that are components of the postsynaptic density (PSD). Two de novos also affected EHMT1, a histone methyl transferase known to directly regulate DLG family members. Using a systems biology approach and merging novel CNV and proteomics data sets, systematic analysis of synaptic protein complexes showed that, compared with control CNVs, case de novos were significantly enriched for the PSD proteome (P=1.72 x 10(-6)). This was largely explained by enrichment for members of the N-methyl-b-aspartate receptor (NMDAR) (P=4.24 x 10(-6)) and neuronal activity-regulated cytoskeleton-associated protein (ARC) (P=3.78 x 10(-6)) postsynaptic signalling complexes. In an analysis of 18 492 subjects (7907 cases and 10 585 controls), case CNVs were enriched for members of the NMDAR complex (P=0.0015) but not ARC (P=0.14). Our data indicate that defects in NMDAR postsynaptic signalling and, possibly, ARC complexes, which are known to be important in synaptic plasticity and cognition, play a significant role in the pathogenesis of schizophrenia. Molecular Psychiatry (2012) 17, 142-153; doi:10.1038/mp.2011.154; published online 15 November 2011 C1 [Kirov, G.; Pocklington, A. J.; Holmans, P.; Ivanov, D.; Georgieva, L.; Grozeva, D.; Fjodorova, M.; Wollerton, R.; Rees, E.; Nikolov, I.; O'Donovan, M. C.; Owen, M. J.] Cardiff Univ, Dept Psychol Med & Neurol, Sch Med, MRC Ctr Neuropsychiat Genet & Genoom,Neurosci & M, Cardiff CF14 4XN, S Glam, Wales. [Ikeda, M.] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan. [Ruderfer, D.; Purcell, S.; Sklar, P.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Ruderfer, D.; Purcell, S.; Sklar, P.] Harvard Univ, Sch Med, Boston, MA USA. [Ruderfer, D.; Purcell, S.; Sklar, P.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ruderfer, D.; Moran, J.; Chambert, K.; Purcell, S.; Sklar, P.] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Toncheva, D.] Univ Hosp Maichin Dom, Sofia, Bulgaria. [van de Lagemaat, L. N.; Bayes, A.; Komiyama, N. H.; Grant, S. G. N.] Univ Edinburgh, Genes Cognit Program, Sch Mol & Clin Med, Edinburgh, Midlothian, Scotland. [Fernandez, E.] KU Leuven Med Sch, VIB Dept Mol & Dev Genet, Louvain, Belgium. [Olason, P. I.; Boettcher, Y.; Stefansson, K.; Stefansson, H.] deCODE Genet, Reykjavik, Iceland. [Collins, M. O.; Choudhary, J.] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. RP Kirov, G (reprint author), Cardiff Univ, Dept Psychol Med & Neurol, Sch Med, MRC Ctr Neuropsychiat Genet & Genoom,Neurosci & M, Henry Wellcome Bldg,Heath Pk, Cardiff CF14 4XN, S Glam, Wales. EM kirov@cardiff.ac.uk RI Bayes, Alex/H-2854-2015; Ruderfer, Douglas/M-5795-2016; Holmans, Peter/F-4518-2015 OI Bayes, Alex/0000-0002-5265-6306; Ruderfer, Douglas/0000-0002-2365-386X; O'Donovan, Michael/0000-0001-7073-2379; Ivanov, Dobril/0000-0001-6271-6301; Moran, Jennifer/0000-0002-5664-4716; Stefansson, Hreinn/0000-0002-9331-6666; Fjodorova, Marija/0000-0002-1852-1408; Holmans, Peter/0000-0003-0870-9412 FU Janssen Research Foundation; Stanley Medical Research Institute; Merck Genome Research Foundation; Herman Foundation; Medical Research Council (MRC) [G0800509]; Centre Grants, the National Institutes of Mental Health (USA) [CONTE: 2 P50 MH066392-05A1]; EU (EU-GEI); EU [HEALTH-2007-2.2.1-10-223423, PIAG-GA-2008-218251, 241995, 242498, 242167]; Genes to Cognition Program; Wellcome Trust; MRC [G06706B]; EMBO; European Commission FX We acknowledge the families who participated in the study. Funding for recruitment was provided by the Janssen Research Foundation. Genotyping was funded by multiple grants to the Stanley Center for Psychiatric Research at the Broad Institute from the Stanley Medical Research Institute, The Merck Genome Research Foundation and the Herman Foundation. Work at Cardiff University was funded by Medical Research Council (MRC) Programme (Ref G0800509) and Centre Grants, the National Institutes of Mental Health (USA) (CONTE: 2 P50 MH066392-05A1) and a grant from the EU (EU-GEI). Genotyping and CNV analysis in the Icelandic trios by deCODE Genetics was funded in part by EU grants: HEALTH-2007-2.2.1-10-223423 (Project PsychCNV), PIAG-GA-2008-218251 (Project PsychGene) and IMI-JU-NewMeds. SGNG, AB, EF, LNVL, JC, NHK and MOC were supported by the Genes to Cognition Program funded by the Wellcome Trust, MRC Project (Ref G06706B), EU grants: (Project GENCODYS Nr 241995, Project EUROSPIN No. 242498 and Project SYNSYS No. 242167). AB is supported by EMBO and the European Commission. We acknowledge Edward Scolnick for helpful discussions. NR 47 TC 278 Z9 279 U1 12 U2 48 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD FEB PY 2012 VL 17 IS 2 BP 142 EP 153 DI 10.1038/mp.2011.154 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 885SZ UT WOS:000299802400007 PM 22083728 ER PT J AU Richards, AL Jones, L Moskvina, V Kirov, G Gejman, PV Levinson, DF Sanders, AR Purcell, S Visscher, PM Craddock, N Owen, MJ Holmans, P O'Donovan, MC AF Richards, A. L. Jones, L. Moskvina, V. Kirov, G. Gejman, P. V. Levinson, D. F. Sanders, A. R. Purcell, S. Visscher, P. M. Craddock, N. Owen, M. J. Holmans, P. O'Donovan, M. C. CA Mol Genetics Schizophrenia ISC TI Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain SO MOLECULAR PSYCHIATRY LA English DT Article DE eQTL; genetics; GWAS; polygenic score; polymorphism; schizophrenia ID CONVERGENT FUNCTIONAL GENOMICS; MISSING HERITABILITY; COMMON VARIANTS; DISEASE; RISK; ARCHITECTURE; VIEWS AB It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. As only a small proportion cif the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and that schizophrenia risk alleles are enriched among single-nucleotide polymorphisms (SNPs) selected for marginal evidence for association (P < 0.5) from genome-wide association studies (GWAS). It follows that if schizophrenia susceptibility alleles are enriched for those that affect gene expression, those marginally associated SNPs, which are also expression quantitative trait loci (eQTLs), should carry more true association signals compared with SNPs that are not marginally associated. To test this, we identified marginally associated (P < 0.5) SNPs from two of the largest available schizophrenia GWAS data sets. We assigned eQTL status to those SNPs based upon an eQTL data set derived from adult human brain. Using the polygenic score method of analysis reported by the ISC, we observed and replicated the observation that higher probability cis-eQTLs predicted schizophrenia better than those with a lower probability for being a cis-eQTL. Our data support the hypothesis that alleles conferring risk of schizophrenia are enriched among those that affect gene expression. Moreover, our data show that notwithstanding the likely developmental origin of schizophrenia, studies of adult brain tissue can, in principle, allow relevant susceptibility eQTLs to be identified. Molecular Psychiatry (2012) 17, 193-201; doi:10.1038/mp.2011.11; published online 22 February 2011 C1 [Richards, A. L.; Jones, L.; Moskvina, V.; Kirov, G.; Craddock, N.; Owen, M. J.; Holmans, P.; O'Donovan, M. C.] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol, Sch Med, Cardiff CF14 4XN, S Glam, Wales. [Gejman, P. V.; Sanders, A. R.] Northshore Univ Hlth Syst Res Inst, Ctr Psychiat Genet, Dept Psychiat & Behav Sci, Evanston, IL USA. [Levinson, D. F.] Stanford Univ, Dept Psychiat, Stanford, CA 94305 USA. [Purcell, S.] Psychiat & Neurodev Genet Unit, Boston, MA USA. [Purcell, S.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Purcell, S.] Broad Inst Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Purcell, S.] MIT, Cambridge, MA 02139 USA. [Visscher, P. M.] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia. RP O'Donovan, MC (reprint author), Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol, Sch Med, Henry Wellcome Bldg, Cardiff CF14 4XN, S Glam, Wales. EM odonovanmc@Cardiff.ac.uk RI macedo santos, antonio/M-5737-2013; Holmans, Peter/F-4518-2015; Ruderfer, Douglas/M-5795-2016; McQuillin, Andrew/C-1623-2008; Morley, Christopher P/K-1907-2014; OI lichtenstein, paul/0000-0003-3037-5287; macedo santos, antonio/0000-0003-2180-2718; Visscher, Peter/0000-0002-2143-8760; Holmans, Peter/0000-0003-0870-9412; Ruderfer, Douglas/0000-0002-2365-386X; McQuillin, Andrew/0000-0003-1567-2240; O'Donovan, Michael/0000-0001-7073-2379; Morley, Christopher P/0000-0003-0185-7148; Escott-Price, Valentina/0000-0003-1784-5483 FU MRC; Wellcome Trust; NIMH (USA) CONTE [2 P50 MH066392-05A1] FX This work was supported by grants from the MRC and the Wellcome Trust. AR was initially supported by a MRC PhD studentship, and subsequently by NIMH (USA) CONTE Award: 2 P50 MH066392-05A1. NR 33 TC 51 Z9 51 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD FEB PY 2012 VL 17 IS 2 BP 193 EP 201 DI 10.1038/mp.2011.11 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 885SZ UT WOS:000299802400012 PM 21339752 ER PT J AU Sansone, SA Rocca-Serra, P Field, D Maguire, E Taylor, C Hofmann, O Fang, H Neumann, S Tong, WD Amaral-Zettler, L Begley, K Booth, T Bougueleret, L Burns, G Chapman, B Clark, T Coleman, LA Copeland, J Das, S de Daruvar, A de Matos, P Dix, I Edmunds, S Evelo, CT Forster, MJ Gaudet, P Gilbert, J Goble, C Griffin, JL Jacob, D Kleinjans, J Harland, L Haug, K Hermjakob, H Sui, SJH Laederach, A Liang, SG Marshall, S McGrath, A Merrill, E Reilly, D Roux, M Shamu, CE Shang, CA Steinbeck, C Trefethen, A Williams-Jones, B Wolstencroft, K Xenarios, I Hide, W AF Sansone, Susanna-Assunta Rocca-Serra, Philippe Field, Dawn Maguire, Eamonn Taylor, Chris Hofmann, Oliver Fang, Hong Neumann, Steffen Tong, Weida Amaral-Zettler, Linda Begley, Kimberly Booth, Tim Bougueleret, Lydie Burns, Gully Chapman, Brad Clark, Tim Coleman, Lee-Ann Copeland, Jay Das, Sudeshna de Daruvar, Antoine de Matos, Paula Dix, Ian Edmunds, Scott Evelo, Chris T. Forster, Mark J. Gaudet, Pascale Gilbert, Jack Goble, Carole Griffin, Julian L. Jacob, Daniel Kleinjans, Jos Harland, Lee Haug, Kenneth Hermjakob, Henning Sui, Shannan J. Ho Laederach, Alain Liang, Shaoguang Marshall, Stephen McGrath, Annette Merrill, Emily Reilly, Dorothy Roux, Magali Shamu, Caroline E. Shang, Catherine A. Steinbeck, Christoph Trefethen, Anne Williams-Jones, Bryn Wolstencroft, Katherine Xenarios, Ioannis Hide, Winston TI Toward interoperable bioscience data SO NATURE GENETICS LA English DT Editorial Material AB To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' framework to support that vision. C1 [Sansone, Susanna-Assunta; Rocca-Serra, Philippe; Maguire, Eamonn; Trefethen, Anne] Univ Oxford, Oxford E Res Ctr, Oxford, England. [Field, Dawn; Taylor, Chris; Booth, Tim] Wallingford Ctr Ecol & Hydrol CEH, Environm Bioinformat Ctr, Nat Environm Res Council, Oxford, England. [Taylor, Chris; de Matos, Paula; Haug, Kenneth; Hermjakob, Henning; Steinbeck, Christoph] European Bioinformat Inst, European Mol Biol Lab EMBL Outstn, Cambridge, England. [Hofmann, Oliver; Begley, Kimberly; Chapman, Brad; Sui, Shannan J. Ho; Hide, Winston] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Fang, Hong] US FDA, ICF Int, Natl Ctr Toxicol Res, Jefferson, AR USA. [Neumann, Steffen] Leibniz Inst Plant Biochem, Dept Stress & Dev Biol, Halle, Germany. [Tong, Weida] US FDA, Ctr Bioinformat, Natl Ctr Toxicol Res, Jefferson, AR USA. [Amaral-Zettler, Linda] Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA. [Begley, Kimberly] Ontario Inst Canc Res Informat & Biocomp, Toronto, ON, Canada. [Bougueleret, Lydie; Xenarios, Ioannis] Swiss Prot Grp, Swiss Inst Bioinformat, Geneva, Switzerland. [Burns, Gully] Univ So Calif, Inst Informat Sci, Marina Del Rey, CA 90292 USA. [Clark, Tim; Das, Sudeshna] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Clark, Tim; Das, Sudeshna; Merrill, Emily] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Coleman, Lee-Ann] British Lib, London, England. [Copeland, Jay; Shamu, Caroline E.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [de Daruvar, Antoine] Univ Bordeaux, Lab Bordelais Rech lnformat LaBRI, CNRS, UMR 5800, Talence, France. [de Daruvar, Antoine; Jacob, Daniel] Univ Bordeaux, Ctr Bioinformat Bordeaux CBiB, Bordeaux, France. [Dix, Ian] AstraZeneca Plc, Knowledge Engn & Informat Sci, Discovery Informat, Macclesfield, Cheshire, England. [Edmunds, Scott; Liang, Shaoguang] BGI Shenzhen, Yantian, Peoples R China. [Evelo, Chris T.] Maastricht Univ, Dept Bioinformat BiGCaT, Maastricht, Netherlands. [Evelo, Chris T.] Netherlands Bioinformat Ctr, NBIC Fac, Nijmegen, Netherlands. [Forster, Mark J.] Syngenta RDIS, Bracknell, Berks, England. [Gaudet, Pascale] Northwestern Univ, Ctr Genet Med, Chicago, IL 60611 USA. [Gaudet, Pascale] Swiss Inst Bioinformat Computat Anal & Lab Invest, Geneva, Switzerland. [Gilbert, Jack] Argonne Natl Lab, Argonne, IL 60439 USA. [Goble, Carole; Wolstencroft, Katherine] Univ Manchester, Sch Comp Sci, Manchester, Lancs, England. [Griffin, Julian L.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. [Griffin, Julian L.] Univ Cambridge, Cambridge Syst Biol Ctr, Cambridge, England. [Griffin, Julian L.] Med Res Council MRC Human Nutr Res, Elsie Widdowson Lab, Cambridge, England. [Jacob, Daniel] INRA, Fruit Biol & Pathol Ctr, UMR 1332, Villenave Dornon, France. [Kleinjans, Jos] PA Maastricht Univ, Dept Toxicogenom, Netherlands Toxicogenom Ctr, Maastricht, Netherlands. [Harland, Lee; Williams-Jones, Bryn] ConnectedDiscovery, London, England. [Laederach, Alain] Univ N Carolina, Dept Biol, Chapel Hill, NC USA. [Marshall, Stephen; Reilly, Dorothy] Novartis Inst BioMed Res, Quantitat Biol Unit, Cambridge, MA USA. [McGrath, Annette] CSIRO Math Informat & Stat, Canberra, ACT, Australia. [Roux, Magali] CNRS UPS76, Inst Sci & Technol Informat, Vandoeuvre Les Nancy, France. [Roux, Magali] Univ Paris 06, CNRS UMR 7606, Paris, France. [Shang, Catherine A.] Macquarie Univ, Sydney, NSW 2109, Australia. [Xenarios, Ioannis] Vital IT, Swiss Inst Bioinformat, Lausanne, Switzerland. RP Sansone, SA (reprint author), Univ Oxford, Oxford E Res Ctr, Oxford, England. EM susanna-assunta.sansone@oerc.ox.ac.uk RI Steinbeck, Christoph/B-4131-2008; Neumann, Steffen/K-5554-2012; Kleinjans, Jos/E-7241-2015; Trivedi, Kruti/E-7558-2015; Evelo, Chris/D-2914-2009; Haug, Ove Kenneth/D-8694-2017; OI Sansone, Susanna-Assunta/0000-0001-5306-5690; Chapman, Brad/0000-0002-3026-1856; Hide, Winston/0000-0002-8621-3271; Goble, Carole/0000-0003-1219-2137; Burns, Gully/0000-0003-1493-865X; Neumann, Steffen/0000-0002-7899-7192; Evelo, Chris/0000-0002-5301-3142; Haug, Ove Kenneth/0000-0003-3168-4145; Coleman, Lee-Ann/0000-0001-5313-8394; Edmunds, Scott/0000-0001-6444-1436; Laederach, Alain/0000-0002-5088-9907; Hofmann, Oliver/0000-0002-7738-1513; Xenarios, Ioannis/0000-0002-3413-6841 FU Biotechnology and Biological Sciences Research Council [BBG0102181, BB/D006422/1, BB/E025080/1, BB/G010218/1, BB/H024921/1, BB/I000771/1, BB/I000860/1, BB/I000917/1, BB/I000933/1, BB/I004637/1, BB/I025840/1]; Medical Research Council [MC_UP_A090_1006, UD99999906]; NCI NIH HHS [1RC2CA148222-01, RC2 CA148222]; NCRR NIH HHS [S10 RR031865, U24 RR025736, U24-RR025736]; NHGRI NIH HHS [U54 HG006097]; NHLBI NIH HHS [R01 HL111527]; NIGMS NIH HHS [R00 GM079953, R01 GM083871, R01 GM101237, R01-GM083871, U24 GM104203]; NIMH NIH HHS [R21 MH087336] NR 29 TC 109 Z9 110 U1 2 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD FEB PY 2012 VL 44 IS 2 BP 121 EP 126 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 883WA UT WOS:000299664400006 PM 22281772 ER PT J AU Kauer, TM Figueiredo, JL Hingtgen, S Shah, K AF Kauer, Timo M. Figueiredo, Jose-Luiz Hingtgen, Shawn Shah, Khalid TI Encapsulated therapeutic stem cells implanted in the tumor resection cavity induce cell death in gliomas SO NATURE NEUROSCIENCE LA English DT Article ID GLIOBLASTOMA-MULTIFORME CELLS; RADIOTHERAPY PLUS CONCOMITANT; IN-VIVO; S-TRAIL; ADJUVANT TEMOZOLOMIDE; MALIGNANT GLIOMA; BRAIN-TUMORS; APOPTOSIS; DELIVERY; CANCER AB Therapeutically engineered stem cells have shown promise for glioblastoma multiforme (GBM) therapy; however, key preclinical studies are urgently needed for their clinical translation. In this study, we investigated a new approach to GBM treatment using therapeutic stem cells encapsulated in biodegradable, synthetic extracellular matrix (sECM) in mouse models of human GBM resection. Using multimodal imaging, we first showed quantitative surgical debulking of human GBM tumors in mice, which resulted in increased survival. Next, sECM encapsulation of engineered stem cells increased their retention in the tumor resection cavity, permitted tumor-selective migration and release of diagnostic and therapeutic proteins in vivo. Simulating the clinical scenario of GBM treatment, the release of tumor-selective S-TRAIL (secretable tumor necrosis factor apoptosis inducing ligand) from sECM-encapsulated stem cells in the resection cavity eradicated residual tumor cells by inducing caspase-mediated apoptosis, delayed tumor regrowth and significantly increased survival of mice. This study demonstrates the efficacy of encapsulated therapeutic stem cells in mouse models of GBM resection and may have implications for developing effective therapies for GBM. C1 [Kauer, Timo M.; Figueiredo, Jose-Luiz; Hingtgen, Shawn; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA 02114 USA. [Kauer, Timo M.; Figueiredo, Jose-Luiz; Hingtgen, Shawn; Shah, Khalid] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shah, Khalid] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shah, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA 02114 USA. EM kshah@helix.mgh.harvard.edu FU Alliance for Cancer Cell and Gene Therapy; American Cancer Society; James McDonald Foundation FX We thank G. Prestwich (University of Utah) and T. Zarembinski (Biotime Inc.) for providing us with sECMs, H. Wakimoto (Massachusetts General Hospital) for providing the primary GBM lines and D. Bhere for critical reading of the manuscript. This work was supported by the Alliance for Cancer Cell and Gene Therapy (K.S.), American Cancer Society (K.S.) and James McDonald Foundation (K.S.). NR 50 TC 63 Z9 64 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD FEB PY 2012 VL 15 IS 2 BP 197 EP 204 DI 10.1038/nn.3019 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 882ZX UT WOS:000299603500010 PM 22197831 ER PT J AU Baron, R AF Baron, Roland TI OSTEOPOROSIS IN 2011 Osteoporosis therapy-dawn of the post-bisphosphonate era SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Editorial Material ID POSTMENOPAUSAL OSTEOPOROSIS; DENOSUMAB; FRACTURES; WOMEN; SOST AB Over the past decade, investigators have actively searched for safer therapeutic approaches to replace or complement the use of bisphosphonates and/or parathyroid hormone, exploring both antiresorptive and osteoanabolic pathways. Besides marked progress in basic research, the year 2011 has seen several compounds for the treatment of osteoporosis enter or progress within clinical trials. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA 02115 USA. RP Baron, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, 188 Longwood Ave, Boston, MA 02115 USA. EM roland_baron@hms.harvard.edu NR 10 TC 10 Z9 14 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 EI 1759-5037 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD FEB PY 2012 VL 8 IS 2 BP 76 EP 78 DI 10.1038/nrendo.2011.207 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 881NO UT WOS:000299493600005 PM 22143180 ER PT J AU Williams, WW Taheri, D Tolkoff-Rubin, N Colvin, RB AF Williams, Winfred W. Taheri, Diana Tolkoff-Rubin, Nina Colvin, Robert B. TI Clinical role of the renal transplant biopsy SO NATURE REVIEWS NEPHROLOGY LA English DT Review ID ANTIBODY-MEDIATED REJECTION; POLYOMAVIRUS-ASSOCIATED NEPHROPATHY; CHRONIC HUMORAL REJECTION; GENE-EXPRESSION PROFILES; KIDNEY-TRANSPLANTATION; ALLOGRAFT-REJECTION; PROTOCOL BIOPSIES; MESSENGER-RNA; THROMBOTIC MICROANGIOPATHY; COLLAPSING GLOMERULOPATHY AB Percutaneous needle core biopsy is the definitive procedure by which essential diagnostic and prognostic information on acute and chronic renal allograft dysfunction is obtained. The diagnostic value of the information so obtained has endured for over three decades and has proven crucially important in shaping strategies for therapeutic intervention. This Review provides a broad outline of the utility of performing kidney graft biopsies after transplantation, highlighting the relevance of biopsy findings in the immediate and early post-transplant period (from days to weeks after implantation), the first post-transplant year, and the late period (beyond the first year). We focus on how biopsy findings change over time, and the wide variety of pathological features that characterize the major clinical diagnoses facing the clinician. This article also includes a discussion of acute cellular and humoral rejection, the toxic effects of calcineurin inhibitors, and the widely varying etiologies and characteristics of chronic lesions. Emerging technologies based on gene expression analyses and proteomics, the in situ detection of functionally relevant molecules, and new bioinformatic approaches that hold the promise of improving diagnostic precision and developing new, refined molecular pathways for therapeutic intervention are also presented. C1 [Williams, Winfred W.; Tolkoff-Rubin, Nina] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Taheri, Diana; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Taheri, Diana; Colvin, Robert B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Williams, WW (reprint author), Massachusetts Gen Hosp, Transplant Ctr, 55 Fruit St, Boston, MA 02114 USA. EM wwwilliams@partners.org FU NIH; Roche Organ Transplant Research Foundation FX The authors thank the NIH and the Roche Organ Transplant Research Foundation for grant support and A. Bernard Collins, Martin Selig and Patricia Della Pelle for their outstanding technical contributions to biopsy analysis. NR 101 TC 27 Z9 30 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD FEB PY 2012 VL 8 IS 2 BP 110 EP 121 DI 10.1038/nrneph.2011.213 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 888AK UT WOS:000299976000010 PM 22231130 ER PT J AU Wijman, CAC Smirnakis, SM Vespa, P Szigeti, K Ziai, WC Ning, MM Rosand, J Hanley, DF Geocadin, R Hall, C Le Roux, PD Suarez, JI Zaidat, OO AF Wijman, C. A. C. Smirnakis, S. M. Vespa, P. Szigeti, K. Ziai, W. C. Ning, M. M. Rosand, J. Hanley, D. F. Geocadin, R. Hall, C. Le Roux, P. D. Suarez, J. I. Zaidat, O. O. CA First Neurocritical Care Res Conf TI Research and Technology in Neurocritical Care SO NEUROCRITICAL CARE LA English DT Review DE Neurocritical care; Neuromonitoring; Genomics; Neuroimaging; Biomarkers ID TRAUMATIC BRAIN-INJURY; CUMULATIVE RADIATION-EXPOSURE; TISSUE OXYGEN-TENSION; LEVEL-DEPENDENT MRI; INTRACEREBRAL HEMORRHAGE; SUBARACHNOID HEMORRHAGE; CEREBRAL MICRODIALYSIS; VEGETATIVE STATE; WIDE ASSOCIATION; VISUAL-CORTEX AB The daily practice of neurointensivists focuses on the recognition of subtle changes in the neurological examination, interactions between the brain and systemic derangements, and brain physiology. Common alterations such as fever, hyperglycemia, and hypotension have different consequences in patients with brain insults compared with patients of general medical illness. Various technologies have become available or are currently being developed. The session on "research and technology" of the first neurocritical care research conference held in Houston in September of 2009 was devoted to the discussion of the current status, and the research role of state-of-the art technologies in neurocritical patients including multi-modality neuromonitoring, biomarkers, neuroimaging, and "omics" research (proteomix, genomics, and metabolomics). We have summarized the topics discussed in this session. We have provided a brief overview of the current status of these technologies, and put forward recommendations for future research applications in the field of neurocritical care. C1 [Wijman, C. A. C.] Stanford Univ, Med Ctr, Stanford Neurocrit Care Program, Palo Alto, CA 94304 USA. [Wijman, C. A. C.] Stanford Univ, Dept Neurol, Palo Alto, CA 94304 USA. [Smirnakis, S. M.; Szigeti, K.; Suarez, J. I.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Smirnakis, S. M.] Baylor Coll Med, Div Neurosci, Houston, TX 77030 USA. [Vespa, P.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Ziai, W. C.; Hanley, D. F.; Geocadin, R.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Ning, M. M.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rosand, J.; Hall, C.] UT SW Univ, Dept Neurol, Dallas, TX USA. [Le Roux, P. D.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Zaidat, O. O.] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. RP Wijman, CAC (reprint author), Stanford Univ, Med Ctr, Stanford Neurocrit Care Program, 780 Welch Rd,Suite 205, Palo Alto, CA 94304 USA. EM cwijman@stanford.edu RI Mandava, Pitchaiah/B-6046-2013; Diringer, Michael/C-1165-2008; OI Mandava, Pitchaiah/0000-0003-4957-4518; Diringer, Michael/0000-0003-2337-5537; Bleck, Thomas/0000-0002-8267-9787 FU National Institute of Neurological Disorders and Stroke [R13NS065494]; Integra Foundation; Neuroscience Center of the St Luke's Episcopal Hospital in Houston, TX FX The First Neurocritical Care Research Conference was funded by award R13NS065494 from the National Institute of Neurological Disorders and Stroke (P. I.: JI Suarez), the Integra Foundation, and the Neuroscience Center of the St Luke's Episcopal Hospital in Houston, TX, and endorsed by the Neurocritical Care Society. NR 58 TC 5 Z9 5 U1 2 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD FEB PY 2012 VL 16 IS 1 BP 42 EP 54 DI 10.1007/s12028-011-9609-5 PG 13 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 881QW UT WOS:000299502500007 PM 21796494 ER PT J AU Tosun, D Rosen, H Miller, BL Weiner, MW Schuff, N AF Tosun, Duygu Rosen, Howard Miller, Bruce L. Weiner, Michael W. Schuff, Norbert TI MRI patterns of atrophy and hypoperfusion associations across brain regions in frontotemporal dementia SO NEUROIMAGE LA English DT Article DE Brain atrophy; Brain hypoperfusion; Dementia; Neurodegenerative diseases; Joint ICA; Multimodality MRI ID MILD COGNITIVE IMPAIRMENT; CEREBRAL-BLOOD-FLOW; ALZHEIMERS-DISEASE; LOBAR DEGENERATION; SEMANTIC DEMENTIA; CORTICOBASAL DEGENERATION; SUPRANUCLEAR PALSY; GLUCOSE-METABOLISM; PERFUSION MRI; IMAGING DATA AB Magnetic Resonance Imaging (MRI) provides various imaging modes to study the brain. We tested the benefits of a joint analysis of multimodality MRI data in combination with a large-scale analysis that involved simultaneously all image voxels using joint independent components analysis (jICA) and compared the outcome to results using conventional voxel-by-voxel unimodality tests. Specifically, we designed a jICA to decompose multimodality MRI data into independent components that explain joint variations between the image modalities as well as variations across brain regions. We tested the jICA design on structural and perfusion-weighted MRI data from 12 patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and 12 cognitively normal elderly individuals. While unimodality analyses showed widespread brain atrophy and hypoperfusion in the patients, jICA further revealed two significant joint components of variations between atrophy and hypoperfusion across brain regions. The 1st joint component revealed associated brain atrophy and hypoperfusion predominantly in the right brain hemisphere in behavioral variant frontotemporal dementia, and the 2nd joint component revealed greater atrophy relative to hypoperfusion affecting predominantly the left hemisphere in behavioral variant frontotemporal dementia. The patterns are consistent with the clinical symptoms of behavioral variant frontotemporal dementia that relate to asymmetric compromises of the left and right brain hemispheres. The joint components also revealed that that structural alterations can be associated with physiological alterations in spatially separated but potentially connected brain regions. Finally, jICA outperformed voxel-by-voxel unimodal tests significantly in terms of an effect size, separating the behavioral variant frontotemporal dementia patients from the controls. Taken together, the results demonstrate the benefit of multimodality MRI in conjunction with jICA for mapping neurodegeneration, which may lead ultimately to an improved diagnosis of behavioral variant frontotemporal dementia and other forms of neurodegenerative diseases. (C) 2011 Elsevier Inc. All rights reserved. C1 [Tosun, Duygu; Weiner, Michael W.; Schuff, Norbert] Vet Affairs Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Rosen, Howard; Miller, Bruce L.] Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Rosen, Howard; Miller, Bruce L.; Weiner, Michael W.; Schuff, Norbert] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Tosun, Duygu; Weiner, Michael W.; Schuff, Norbert] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Tosun, D (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Bldg 13,114M, San Francisco, CA 94121 USA. EM duygu.tosun@ucsf.edu FU National Institutes of Health [P41 RR23953, P01 AG019724]; Department of Defense [W81XWH-05-2-0094] FX This work was supported by the National Institutes of Health grant P41 RR23953 and P01 AG019724, and the Department of Defense grant W81XWH-05-2-0094. This work has also been made possible by use of research facilities at the Veteran Affairs Medical Center in San Francisco. NR 57 TC 9 Z9 10 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2012 VL 59 IS 3 BP 2098 EP 2109 DI 10.1016/j.neuroimage.2011.10.031 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 881NS UT WOS:000299494000013 PM 22036676 ER PT J AU Miller, KL McNab, JA Jbabdi, S Douaud, G AF Miller, Karla L. McNab, Jennifer A. Jbabdi, Saad Douaud, Gwenaelle TI Diffusion tractography of post-mortem human brains: Optimization and comparison of spin echo and steady-state free precession techniques SO NEUROIMAGE LA English DT Article DE Diffusion; Tractography; Post mortem; Steady-state free precession; DTI ID FIXED HUMAN BRAIN; WHITE-MATTER; FORMALIN FIXATION; WATER RELAXATION; FIBER PATHWAYS; NERVOUS-TISSUE; PRIMATE BRAIN; MR-IMAGES; SENSITIVITY; TRACKING AB Diffusion imaging of post-mortem brains could provide valuable data for validation of diffusion tractography of white matter pathways. Long scans (e.g., overnight) may also enable high-resolution diffusion images for visualization of fine structures. However, alterations to post-mortem tissue (T2 and diffusion coefficient) present significant challenges to diffusion imaging with conventional diffusion-weighted spin echo (DW-SE) acquisitions, particularly for imaging human brains on clinical scanners. Diffusion-weighted steady-state free precession (DW-SSFP) has been proposed as an alternative acquisition technique to ameliorate this tradeoff in large-bore clinical scanners. In this study, both DWSE and DW-SSFP are optimized for use in fixed white matter on a clinical 3-Tesla scanner. Signal calculations predict superior performance from DW-SSFP across a broad range of protocols and conditions. DW-SE and DW-SSFP data in a whole, post-mortem human brain are compared for 6- and 12-hour scan durations. Tractography is performed in major projection, commissural and association tracts (corticospinal tract, corpus callosum, superior longitudinal fasciculus and cingulum bundle). The results demonstrate superior tract-tracing from DW-SSFP data, with 6-hour DW-SSFP data performing as well as or better than 12-hour DW-SE scans. These results suggest that DW-SSFP may be a preferred method for diffusion imaging of post-mortem human brains. The ability to estimate multiple fibers in imaging voxels is also demonstrated, again with greater success in DW-SSFP data. (C) 2011 Elsevier Inc. All rights reserved. C1 [Miller, Karla L.; Jbabdi, Saad; Douaud, Gwenaelle] Univ Oxford, FMRIB Ctr, Nuffield Dept Clin Neurosci, Oxford, England. [McNab, Jennifer A.] Massachusetts Gen Hosp, AA Martinos Ctr, Boston, MA 02114 USA. RP Miller, KL (reprint author), John Radcliffe Hosp, FMRIB Ctr, Oxford OX3 9DU, England. EM karla@fmrib.ox.ac.uk OI Miller, Karla/0000-0002-2511-3189; Jbabdi, Saad/0000-0003-3234-5639 FU Charles Wolfson Charitable Trust; Wellcome Trust FX This work was funded by the Charles Wolfson Charitable Trust and the Wellcome Trust. The authors are grateful to the Thomas Willis Brain Collection for the brain specimen used in this study, and to Drs. Heidi Johansen-Berg and Charlotte Stagg for useful discussions. NR 52 TC 17 Z9 17 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2012 VL 59 IS 3 BP 2284 EP 2297 DI 10.1016/j.neuroimage.2011.09.054 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 881NS UT WOS:000299494000030 PM 22008372 ER PT J AU Gagnon, L Cooper, RJ Yucel, MA Perdue, KL Greve, DN Boas, DA AF Gagnon, Louis Cooper, Robert J. Yuecel, Meryem A. Perdue, Katherine L. Greve, Douglas N. Boas, David A. TI Short separation channel location impacts the performance of short channel regression in NIRS SO NEUROIMAGE LA English DT Article DE Near-Infrared Spectroscopy; Systemic interference; Short optode separations; Kalman filtering ID NEAR-INFRARED SPECTROSCOPY; HEMODYNAMIC-RESPONSES; BRAIN ACTIVATION; HUMAN ADULTS; TOMOGRAPHY; MOTOR; FMRI AB Near-Infrared Spectroscopy (NIRS) allows the recovery of cortical oxy- and deoxyhemoglobin changes associated with evoked brain activity. NIRS is a back-reflection measurement making it very sensitive to the superficial layers of the head, i.e. the skin and the skull, where systemic interference occurs. As a result, the NIRS signal is strongly contaminated with systemic interference of superficial origin. A recent approach to overcome this problem has been the use of additional short source-detector separation optodes as regressors. Since these additional measurements are mainly sensitive to superficial layers in adult humans, they can be used to remove the systemic interference present in longer separation measurements, improving the recovery of the cortical hemodynamic response function (HRF). One question that remains to answer is whether or not a short separation measurement is required in close proximity to each long separation NIRS channel. Here, we show that the systemic interference occurring in the superficial layers of the human head is inhomogeneous across the surface of the scalp. As a result, the improvement obtained by using a short separation optode decreases as the relative distance between the short and the long measurement is increased. NIRS data was acquired on 6 human subjects both at rest and during a motor task consisting of finger tapping. The effect of distance between the short and the long channel was first quantified by recovering a synthetic hemodynamic response added over the resting-state data. The effect was also observed in the functional data collected during the finger tapping task. Together, these results suggest that the short separation measurement must be located as close as 1.5 cm from the standard NIRS channel in order to provide an improvement which is of practical use. In this case, the improvement in Contrast-to-Noise Ratio (CNR) compared to a standard General Linear Model (GLM) procedure without using any small separation optode reached 50% for HbO and 100% for HbR. Using small separations located farther than 2 cm away resulted in mild or negligible improvements only. (C) 2011 Elsevier Inc. All rights reserved. C1 [Gagnon, Louis; Boas, David A.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gagnon, Louis; Cooper, Robert J.; Yuecel, Meryem A.; Greve, Douglas N.; Boas, David A.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA USA. [Gagnon, Louis] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Perdue, Katherine L.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Gagnon, L (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM lgagnon@nmr.mgh.harvard.edu RI Perdue, Katherine/D-4306-2013; OI Perdue, Katherine/0000-0003-2846-3149; Cooper, Robert/0000-0001-6696-8020 FU NIH [P41-RR14075, R01-EB006385]; Fonds Quebecois sur la Nature et les Technologies FX The authors are grateful to Drs. Evgeniya Kirilina, Yunjie Tong and Blaise deB. Frederick for fruitful discussions about cerebrovascular physiology. This work was supported by NIH grants P41-RR14075 and R01-EB006385. L Gagnon was supported by the Fonds Quebecois sur la Nature et les Technologies. NR 46 TC 71 Z9 72 U1 2 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2012 VL 59 IS 3 BP 2518 EP 2528 DI 10.1016/j.neuroimage.2011.08.095 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 881NS UT WOS:000299494000053 PM 21945793 ER PT J AU Ingenbleek, Y McCully, KS AF Ingenbleek, Yves McCully, Kilmer S. TI Vegetarianism produces subclinical malnutrition, hyperhomocysteinemia and atherogenesis SO NUTRITION LA English DT Article DE Protein malnutrition; Lean body mass; Transthyretin; Homocysteine; Sulfur deficiency; Cardiovascular disease ID CARDIOVASCULAR-DISEASE; VASCULAR-DISEASE; SOUTH-ASIA; HOMOCYSTEINE; SULFUR; METABOLISM; PROTEIN; DIET; DETERMINANT; GLUTATHIONE AB Objective: To explain why vegetarian subjects develop morbidity and mortality from cardiovascular diseases unrelated to vitamin B status and Framingham criteria. Methods: A study of 24 rural male subjects 18 to 30 y old and 15 urban male controls was conducted in the Sahel region of Chad. Food consumption was determined from a dietary questionnaire, and overall health status was assessed by body weight, body mass index, serum albumin, plasma transthyretin, urinary nitrogen, and creatinine. Plasma lipids, vitamins B6, BY and B12, homocysteine, and related sulfur amino acids were measured as selected cardiovascular disease risk factors. Results: Body weight, body mass index, blood, and urinary markers of protein status were significantly lower, with an estimated 10% decrease of lean body mass in the study group compared with urban controls. Neither lipid fractions nor plasma levels of vitamins B6, B9, and B12 were significantly different between the two groups. Although the mean consumption of sulfur amino acids (10.4 mg.kg(-1).d(-1)) by rural subjects was significantly below the recommended dietary allowances (13 mg.kg(-1).d(-1)), plasma methionine values were similar in the two groups. In contrast, homocysteine concentration was significantly increased (18.6 mu mol/L, P < 0.001), and the levels of cysteine and glutathione were significantly decreased in the study group, demonstrating inhibition of the trans-sulfuration pathway. The strong negative correlation (r = -0.71) between transthyretin and homocysteine implicated lean body mass as a critical determinant of hyperhomocysteinemia. Conclusion: The low dietary intake of protein and sulfur amino acids by a plant-eating population leads to subclinical protein malnutrition, explaining the origin of hyperhomocysteinemia and the increased vulnerability of these vegetarian subjects to cardiovascular diseases. Published by Elsevier Inc. C1 [McCully, Kilmer S.] VA Boston Healthcare Syst, Pathol & Lab Med Serv, W Roxbury, MA USA. [Ingenbleek, Yves] Univ Strasbourg, Fac Pharm, Lab Nutr, Strasbourg, France. [McCully, Kilmer S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP McCully, KS (reprint author), VA Boston Healthcare Syst, Pathol & Lab Med Serv, W Roxbury, MA USA. EM kilmer.mccully@va.gov FU University Louis Pasteur, Strasbourg, France FX This work was funded by University Louis Pasteur, Strasbourg, France. NR 45 TC 23 Z9 23 U1 3 U2 50 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 EI 1873-1244 J9 NUTRITION JI Nutrition PD FEB PY 2012 VL 28 IS 2 BP 148 EP 153 DI 10.1016/j.nut.2011.04.009 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 882ZW UT WOS:000299603400008 PM 21872435 ER PT J AU Jonker, MA Hermsen, JL Sano, Y Heneghan, AF Lan, JG Kudsk, KA AF Jonker, Mark A. Hermsen, Joshua L. Sano, Yoshifumi Heneghan, Aaron F. Lan, Jinggang Kudsk, Kenneth A. TI Small intestine mucosal immune system response to injury and the impact of parenteral nutrition SO SURGERY LA English DT Article ID POLYMERIC IMMUNOGLOBULIN RECEPTOR; VENTILATOR-ASSOCIATED PNEUMONIA; ENTERAL NUTRITION; SECRETORY IGA; BACTERIAL TRANSLOCATION; SEPTIC MORBIDITY; ABDOMINAL-TRAUMA; LYMPHOID-TISSUE; RISK-FACTORS; ILL PATIENTS AB Background. Both humans and mice increase airway immunoglobulin A (IgA) after injury. This protective response is associated with TNF-alpha, IL-1 beta, and IL-6 airway increases and in mice is dependent upon these cytokines as well as enteral feeding. Parenteral nutrition (PN) with decreased enteral stimulation (DES) alters gut barrier function, decreases intestinal IgA, and decreases the principal IgA transport protein pIgR. We investigated the small intestine (SI) IgA response to injury and the role of TNT-alpha, IL-1 beta, IL-6, and PN/DES. Methods. Expt 1: Murine kinetics of SI washing fluid (SIWF) IgA; SI, SIWF and serum TNT-alpha, IL-1 beta, and IL-6, was determined by ELISA from 0 to 8 hours after a limited surgical stress injury (laparotomy and neck incisions). Expt 2: Mice received chow or PN/DES before injury and SIWF IgA and SI pIgR levels were determined at 0 and 8 hours. Expt 3: Mice received PBS, TNT-alpha antibody, or IL-1 beta antibody 30 minutes before injury to measure effects on the SIWF IgA response. Expt 4: Mice received injury or exogenous TNF-alpha, IL-1 beta, and IL-6 to measure effects on the SIWF IgA response. Results. Expt 1: SIWF IgA levels increased significantly by 2 hours after injury without associated increases in TNT-alpha or IL-1 beta whereas IL-6 was only increased at 1 hour after injury. Expt 2: PN/DES significantly reduced baseline SIWF IgA and SI pIgR and eliminated their increase after injury seen in Chow mice. Expt 3: TNT-alpha and IL-1 beta blockade did not affect the SIWF IgA increase after injury. Expt 4: Exogenous TNT-alpha, IL-1 beta, and IL-6 increased SIWF IgA similarly to injury. Conclusion. The SI mucosal immune responds to injury or exogenous TNF-alpha, IL-1 beta, and IL-6 with an increase in lumen IgA, although it does not rely on local SI increases in TNT-alpha or IL-1 beta as it does in the lung. Similar to the lung, the IgA response is eliminated with.PN/DES. (Surgery 2012;151:278-86.) C1 [Sano, Yoshifumi; Heneghan, Aaron F.; Lan, Jinggang; Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Surg Serv, Madison, WI USA. [Sano, Yoshifumi; Heneghan, Aaron F.; Lan, Jinggang; Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Dept Surg, Madison, WI USA. [Jonker, Mark A.; Hermsen, Joshua L.; Sano, Yoshifumi; Heneghan, Aaron F.; Lan, Jinggang; Kudsk, Kenneth A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU National Institutes of Health [R01 GM53439] FX Supported by National Institutes of Health Grant R01 GM53439 and also based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 44 TC 12 Z9 15 U1 0 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 2012 VL 151 IS 2 BP 278 EP 286 DI 10.1016/j.surg.2010.10.013 PG 9 WC Surgery SC Surgery GA 883BO UT WOS:000299607800017 PM 21145571 ER PT J AU Mulert, C Kirsch, V Whitford, TJ Alvarado, J Pelavin, P McCarley, RW Kubicki, M Salisbury, DF Shenton, ME AF Mulert, Christoph Kirsch, Valerie Whitford, Thomas J. Alvarado, Jorge Pelavin, Paula McCarley, Robert W. Kubicki, Marek Salisbury, Dean F. Shenton, Martha E. TI Hearing voices: A role of interhemispheric auditory connectivity? SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Article DE Schizophrenia; brain imaging; MRI; positive symptoms; biological psychiatry ID WHITE-MATTER; VERBAL HALLUCINATIONS; DTI TRACTOGRAPHY; CORPUS-CALLOSUM; SCHIZOPHRENIA; BRAIN; PATHWAYS; ACTIVATION; TRACKING; SPEECH AB Objectives. Auditory verbal hallucinations (AVH) are among the most common symptoms in schizophrenia. Earlier studies suggest changes in the structural connectivity of auditory areas involved in the pathophysiology of auditory hallucinations. Combining diffusion tensor imaging (DTI) and fibre tractography provides a unique opportunity to visualize and quantify entire fibre bundles. Methods. Fibre tracts connecting homotopic auditory areas via the corpus callosum were identified with DTI in ten first episode paranoid schizophrenia patients and ten healthy controls. Regions of interest were drawn manually, to guide tractography, and fractional anisotropy (FA) - a measure of fibre integrity - was calculated and averaged over the entire tract for each subject. Results. There was no difference in the FA of the interhemispheric auditory fibres between schizophrenic patients and healthy controls. However, the subgroup of patients hearing conversing voices showed increased FA relative to patients without these symptoms (P = 0.047) and trendwise increased FA relative to healthy controls (P = 0.066). In addition, a trendwise correlation between FA values and AVH symptoms (P = 0.089) was found. Conclusions. Our findings suggest that in addition to local deficits in the left auditory cortex and disturbed fronto-temporal connectivity, the interhemispheric auditory pathway might be involved in the pathogenesis of AVH. C1 [Mulert, Christoph; Kirsch, Valerie; Whitford, Thomas J.; Alvarado, Jorge; Pelavin, Paula; McCarley, Robert W.; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02115 USA. [Mulert, Christoph] Univ Med Ctr Hamburg Eppendorf, Dept Psychiat & Psychotherapy, Psychiat Neuroimaging Branch, Hamburg, Germany. [Mulert, Christoph; Kirsch, Valerie] Ludwig Maximilians Univ Munchen, Dept Psychiat, Munich, Germany. [Whitford, Thomas J.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Dept Psychiat, Melbourne, Vic, Australia. [Whitford, Thomas J.] Melbourne Hlth, Melbourne, Vic, Australia. [McCarley, Robert W.; Kubicki, Marek; Shenton, Martha E.] VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA USA. [McCarley, Robert W.; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Salisbury, Dean F.] Harvard Univ, Sch Med, Cognit Neurosci Lab, McLean Hosp,Dept Psychiat, Belmont, MA 02178 USA. [Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Surg Planning Lab, MRI Div,Dept Radiol,Med Sch, Boston, MA 02115 USA. RP Mulert, C (reprint author), Martinistr 52, D-20246 Hamburg, Germany. EM c.mulert@uke.de RI Mulert, Christoph/F-2576-2012; McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU German Society for Psychiatry, Psychotherapy and Neurology; National Health and Medical Research Council of Australia [NHMRC 520627]; Department of Veterans Affairs; National Institute of Health [R01 MH 40799, R01 MH 052807, P50MH080272, R01 MH58704, R01 MH 50740, K05 MH 070047]; NARSAD FX This work was supported by a grant of the German Society for Psychiatry, Psychotherapy and Neurology (Imaging Award 2007)(CM), by an Overseas-Based Biomedical Training Fellowship from the National Health and Medical Research Council of Australia (NHMRC 520627), administered through the Melbourne Neuropsychiatry Centre at the University of Melbourne (TW), by the Department of Veterans Affairs (Merit Award to RWM and to MES, Schizophrenia Center Award to RWM and MES, Middleton Award to RWM), by the National Institute of Health (R01 MH 40799, R01 MH 052807, P50MH080272 to RWM; R01 MH58704 to DFS, and R01 MH 50740 to MES and a K05 MH 070047 award to MES), and NARSAD awards (DFS and MES). Kathrin Holzschneider was involved in the final editing of the paper. NR 31 TC 26 Z9 27 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1562-2975 J9 WORLD J BIOL PSYCHIA JI World J. Biol. Psychiatry PD FEB PY 2012 VL 13 IS 2 BP 153 EP 158 DI 10.3109/15622975.2011.570789 PG 6 WC Psychiatry SC Psychiatry GA 886GT UT WOS:000299842800009 PM 21623667 ER PT J AU Lee, BL Higgins, MJ Goss, PE AF Lee, Brittany L. Higgins, Michaela J. Goss, Paul E. TI Denosumab and the current status of bone-modifying drugs in breast cancer SO ACTA ONCOLOGICA LA English DT Review ID KAPPA-B LIGAND; PLUS ZOLEDRONIC ACID; QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; BIOCHEMICAL MARKERS; RECEPTOR ACTIVATOR; FOLLOW-UP; ENDOCRINE THERAPY; MINERAL DENSITY AB Background. Bone-modifying therapy is a primary research interest in breast cancer. Several features contribute to the importance of the bone environment in the management of breast cancer. Firstly, bone metastases represent the most common site of breast cancer metastases and secondly, the emergence of cancer treatment-induced bone loss (CTIBL) among breast cancer survivors and patients is of increasing concern. Furthermore, concordant with the "seed and soil" theory, agents that alter the bone microenvironment may even prevent tumor cell seeding in bone and limit cancer growth. Material and methods. Medical databases and conference proceedings were searched to identify articles, abstracts and clinical trials that have or are investigating denosumab and bisphosphonates in cancer therapy. Our search included a predefined focus on bone-modifying therapies in early and advanced breast cancer. Results and discussion. Bisphosphonates (BPs) have an established role both in the prevention and treatment of CTIBL and have been studied in the adjuvant setting for early breast cancer (EBC). Denosumab is a monoclonal antibody directed against RANK ligand and thereby inhibits osteoclastogenesis and bone resportion. It is the newest agent approved for the treatment of postmenopausal osteoporosis and the prevention of skeletal-related events (SRE) in cancer patients with solid tumors and bone metastases. Denosumab has a favorable toxicity profile in comparison to BPs and has the potential to improve cancer outcomes. Conclusion. This review examines the existing role of denosumab in the treatment of bone complications of breast cancer and its potential role as adjuvant therapy. C1 [Higgins, Michaela J.; Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Lee, Brittany L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House,LRH 302, Boston, MA 02114 USA. EM pgoss@partners.org FU Avon Foundation, New York FX We would like to thank Mauro Martino for his assistance with Figure 1 preparation. Paul Goss is supported by the Avon Foundation, New York. Paul Goss is the Chair of the D-Care clinical trial. None of the authors have any conflicts of interest to disclose. NR 95 TC 7 Z9 7 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PD FEB PY 2012 VL 51 IS 2 BP 157 EP 167 DI 10.3109/0284186X.2011.633555 PG 11 WC Oncology SC Oncology GA 880DT UT WOS:000299385600003 PM 22150116 ER PT J AU Garvey, WT Ryan, DH Look, M Gadde, KM Allison, DB Peterson, CA Schwiers, M Day, WW Bowden, CH AF Garvey, W. Timothy Ryan, Donna H. Look, Michelle Gadde, Kishore M. Allison, David B. Peterson, Craig A. Schwiers, Michael Day, Wesley W. Bowden, Charles H. TI Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; IMPAIRED GLUCOSE-TOLERANCE; DOUBLE-BLIND; LIFE-STYLE; TOPIRAMATE; EFFICACY; SAFETY; COMBINATION; PREVENTION; MANAGEMENT AB Background: Obesity is a serious chronic disease. Controlled-release phentermine/topiramate (PHEN/TPM CR), as an adjunct to lifestyle modification, has previously shown significant weight loss compared with placebo in a 56-wk study in overweight and obese subjects with >= 2 weight-related comorbidities. Objective: This study evaluated the long-term efficacy and safety of PHEN/TPM CR in overweight and obese subjects with cardiometabolic disease. Design: This was a placebo-controlled, double-blind, 52-wk extension study; volunteers at selected sites continued with original randomly assigned treatment [placebo, 7.5 mg phentermine/46 mg controlled-release topiramate (7.5/46), or 15 mg phentermine/92 mg controlled-release topiramate (15/92)] to complete a total of 108 wk. All subjects participated in a lifestyle-modification program. Results: Of 866 eligible subjects, 676 (78%) elected to continue in the extension. Overall, 84.0% of subjects completed the study, with similar completion rates between treatment groups. At week 108, PHEN/TPM CR was associated with significant, sustained weight loss (intent-to-treat with last observation carried forward; P < 0.0001 compared with placebo); least-squares mean percentage changes from baseline in body weight were -1.8%, -9.3%, and -10.5% for placebo, 7.5/46, and 15/92, respectively. Significantly more PHEN/TPM CR-treated subjects at each close achieved >= 5%, >= 10%, >= 15%, and >= 20% weight loss compared with placebo (P < 0.001). PHEN/TPM CR improved cardiovascular and metabolic variables and decreased rates of incident diabetes in comparison with placebo. PHEN/TPM CR was well tolerated over 108 wk, with reduced rates of adverse events occurring between weeks 56 and 108 compared with rates between weeks 0 and 56. Conclusion: PHEN/TPM CR in conjunction with lifestyle modification may provide a well-tolerated and effective option for the sustained treatment of obesity complicated by cardiometabolic disease. This trial was registered at clinicaltrials.gov as NCT00796367. Am J Clin Nutr 2012;95:297-308. C1 [Garvey, W. Timothy] Univ Alabama, Dept Nutr Sci, UAB Diabet Res & Training Ctr, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Univ Alabama, Dept Med, UAB Diabet Res & Training Ctr, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. [Ryan, Donna H.] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Look, Michelle] San Diego Sports Med, San Diego, CA USA. [Gadde, Kishore M.] Duke Univ, Med Ctr, Obes Clin Trials Program, Durham, NC USA. [Allison, David B.] Univ Alabama, Dept Biostat, UAB Nutr & Obes Res Ctr, Birmingham, AL 35294 USA. [Peterson, Craig A.; Day, Wesley W.; Bowden, Charles H.] Vivus Inc, Mountain View, CA USA. [Schwiers, Michael] Medpace, Cincinnati, OH USA. RP Garvey, WT (reprint author), Univ Alabama, Dept Nutr Sci, UAB Diabet Res & Training Ctr, Webb 232,1675 Univ Blvd, Birmingham, AL 35294 USA. EM garveyt@uab.edu OI Allison, David/0000-0003-3566-9399 FU Vivus Inc; Forest Laboratories; National Institute of Diabetes and Digestive and Kidney Diseases FX Vivus Inc provided funding and essential materials for this study.; The authors' responsibilities were as follows-KMG, DBA, DHR, MS, CAP, WWD, and CHB: designed the research; WTG, KMG, and ML: conducted the research; WTG, KMG, DBA, DHR, CAP, MS, WWD, and CHB: analyzed and interpreted data; WTG, DHR, ML, KMG, DBA, CAP, MS, WWD, and CHB: drafted and edited the manuscript; and MS: had primary responsibility for final content and is the guarantor of the manuscript, having had full access to all of the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis. The external authors as well as those employed by the funding sponsor participated in protocol design, data analyses, interpretation, and preparation of the manuscript. WTG participated in clinical trials with Merck & Co, Inc; Amylin Pharmaceuticals; Vivus Inc; Abbott; and Daiichi-Sankyo. He has served as an advisor, consultant, and/or speaker for Abbott Nutrition, Daiichi-Sankyo, Johnson & Johnson, LipoScience, Tethys, and Vivus Inc. He is a scientific advisory board member for Daiichi-Sankyo and Tethys, and he holds stock in Bristol-Myers Squibb; Isis/Genzyme; Merck & Co, Inc; Pfizer Inc; Novartis Pharmaceuticals Corp; and Vivus Inc. DHR served as a consultant for Vivus but did not receive any payment for service. ML is a scientific advisory board member for Vivus Inc. KMG received research support from Forest Laboratories, the National Institute of Diabetes and Digestive and Kidney Diseases, and Vivus Inc and owns stock in Orexigen Therapeutics. DBA received grants, honoraria, donations, and consulting fees from numerous food, beverage, and pharmaceutical companies, as well as other commercial and nonprofit entities with interests in obesity, including but not limited to Arena Pharmaceuticals, Jason Pharmaceuticals Inc, Pfizer Inc, and Vivus Inc. He served as a board member for the Pfizer Inc VPO program. WWD, CHB, and CAP are employees of Vivus Inc. MS was employed as the lead statistician for Medpace Inc, the study Contract Research Organization, throughout the study design, execution, and analysis; he had no additional conflicts to disclose. NR 34 TC 183 Z9 185 U1 1 U2 24 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2012 VL 95 IS 2 BP 297 EP 308 DI 10.3945/ajcn.111.024927 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 883QC UT WOS:000299647800007 PM 22158731 ER PT J AU Sharma, TS Bechard, LJ Feldman, HA Venick, R Gura, K Gordon, CM Sonis, A Guinan, EC Duggan, C AF Sharma, Tanvi S. Bechard, Lori J. Feldman, Henry A. Venick, Robert Gura, Kathleen Gordon, Catherine M. Sonis, Andrew Guinan, Eva C. Duggan, Christopher TI Effect of titrated parenteral nutrition on body composition after allogeneic hematopoietic stem cell transplantation in children: a double-blind, randomized, multicenter trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID BONE-MARROW-TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; ENERGY-EXPENDITURE; CHILDHOOD-CANCER; ADULT SURVIVORS; SUPPORT; YOUNG; IRRADIATION; HOMEOSTASIS; POPULATION AB Background: Children undergoing hematopoietic stem cell transplantation (HSCT) often require parenteral nutrition (PN) to optimize caloric intake. Standard approaches to nutritional supplementation provide 130-150% of estimated energy expenditure, but resting energy expenditure (REE) may be lower than expected after HSCT. Provision of PN exceeding energy needs may lead to overfeeding and associated complications. Objective: We conducted a blinded, randomized, controlled, multicenter trial in children undergoing HSCT to determine the effect on body composition of 2 different approaches of nutrition support: standard amounts of energy from PN (130-150% of REE) compared with PN titrated to match measured REE. Design: Twenty-six children undergoing HSCT were randomly assigned to standard or titrated PN. Energy intake was monitored until day 30 after HSCT. Body-composition and anthropometric measures were obtained through day 100. The primary outcome variable was percentage body fat (%BF) measured by dual energy X-ray absorptiometry. Results: The estimated change in %BF from baseline to day 30 was 1.2 +/- 0.5% in the standard group and 0.1 +/- 0.5% in the experimental group, but the overall time course of %BF did not differ significantly by treatment (P = 0.39 for time x treatment interaction). A profound loss of lean body mass (LBM) occurred in both groups during the intervention period and persisted through day 100. Conclusions: Parenteral energy intake titrated to energy expenditure does not result in a lower accumulation of BF than does standard energy intake. Neither titrated nor standard PN regimens during HSCT preserve LBM. Alternative approaches to preserve LBM are needed. This trial is registered at clinicaltrials.gov as 00115258. Am J Clin Nutr 2012;95:342-51. C1 [Sharma, Tanvi S.; Bechard, Lori J.; Feldman, Henry A.; Gura, Kathleen; Gordon, Catherine M.; Sonis, Andrew; Guinan, Eva C.; Duggan, Christopher] Childrens Hosp, Div GI Nutr, Boston, MA 02115 USA. [Bechard, Lori J.; Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Venick, Robert] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA. RP Duggan, C (reprint author), Childrens Hosp, Div GI Nutr, 300 Longwood Ave, Boston, MA 02115 USA. EM christopher.duggan@childrens.harvard.edu FU NCRR [M01-RR02172]; NIH [UL1 RR025758-01, K24 HD 058795] FX Supported by the Massachusetts Vitamin Litigation Grant; grant M01-RR02172 from the NCRR, NIH to Children's Hospital, Boston GCRC; grant UL1 RR025758-01 to the Harvard Catalyst CTSA 1; grant M01-RR00865 to the General Clinical Research Centers Program at UCLA; and NIH K24 HD 058795 (to CD). NR 42 TC 5 Z9 6 U1 0 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2012 VL 95 IS 2 BP 342 EP 351 DI 10.3945/ajcn.111.026005 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 883QC UT WOS:000299647800012 PM 22205317 ER PT J AU Cho, E Lee, JE Rimm, EB Fuchs, CS Giovannucci, EL AF Cho, Eunyoung Lee, Jung Eun Rimm, Eric B. Fuchs, Charles S. Giovannucci, Edward L. TI Alcohol consumption and the risk of colon cancer by family history of colorectal cancer SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID LIFE-STYLE; POLYMORPHISMS; METABOLISM; FOLATE; GENES; WOMEN AB Background: Individuals with a family history of colorectal cancer may be more susceptible to adverse effects of alcohol consumption. Objective: We investigated whether the association between alcohol consumption and colon cancer risk differed by family history of colorectal cancer. Design: We conducted prospective studies in women and men in the Nurses' Health Study and Health Professionals Follow-Up Study, respectively. Alcohol consumption was first assessed in 1980 in women and in 1986 in men. Results: During a follow-up of 26 y among 87,861 women and 20 y among 47,290 men, we documented 1801 cases of colon cancer (1094 women and 707 men). Higher alcohol consumption was associated with an elevated risk of colon cancer, although the association was significant only for the highest intake category of >= 30 g/d, with no significant linear trend. The association between alcohol consumption and colon cancer risk differed by family history of colorectal cancer; in comparison with nondrinkers, the pooled multivariate RRs for alcohol consumption of >= 30 g/d were 1.23 (95% CI: 0.96, 1.57; NS) among those with no family history and 2.02 (95% CI: 1.30, 3.13) among those with a family history of colorectal cancer (P value test for difference = 0.05). In comparison with nondrinkers with no family history, the RR for colon cancer was 2.80 (95% CI: 2.00, 3.91) for individuals who consumed >= 30 g/d and who had a family history of colorectal cancer. Conclusion: Reducing alcohol consumption may decrease the incidence of colon cancer, especially among those with a family history of colorectal cancer. Am J Clin Nutr 2012:95:413-9. C1 [Cho, Eunyoung; Lee, Jung Eun; Rimm, Eric B.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Cho, Eunyoung; Lee, Jung Eun; Rimm, Eric B.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA. [Cho, Eunyoung; Rimm, Eric B.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Rimm, Eric B.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Seoul, South Korea. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Cho, E (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM eunyoung.cho@channing.harvard.edu OI Lee, Jung Eun/0000-0003-1141-878X FU NIH [AA017693, CA87969, CA55075] FX Supported by research grants AA017693, CA87969, and CA55075 from the NIH. NR 23 TC 14 Z9 14 U1 1 U2 6 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2012 VL 95 IS 2 BP 413 EP 419 DI 10.3945/ajcn.111.022145 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 883QC UT WOS:000299647800020 PM 22218161 ER PT J AU Busarla, SVP Sayed, S Nazarian, RM Gimbel, DC Moloo, Z Sohani, AR AF Busarla, Satya Vara Prasad Sayed, Shahin Nazarian, Rosalynn M. Gimbel, Devon C. Moloo, Zahir Sohani, Aliyah R. TI Kaposi Sarcoma in Association With Molluscum Contagiosum: An Uncommon Diagnosis in a Single Biopsy and Potential Diagnostic Pitfall SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE Kaposi sarcoma; molluscum contagiosum; human immunodeficiency virus; human herpes virus-8; latency-associated nuclear antigen-1 ID SKIN-LESION; AIDS; PATIENT; VIRUS; CRYPTOCOCCOSIS; DISEASE AB Molluscum contagiosum is a cutaneous poxviral infection that is rarely associated with other skin diseases, such as cutaneous neoplasms. Such associations are likely to be coincidental, except in immunocompromised patients. Kaposi sarcoma, an angioproliferative neoplasm derived from lymphatic endothelium, is mediated by human herpes virus-8 infection and occurs with increased frequency in immunocompromised individuals. We report an unusual case of molluscum contagiosum with underlying cutaneous Kaposi sarcoma diagnosed in a single skin biopsy of a human immunodeficiency virus-positive patient. Our case highlights the importance of adequate sampling to avoid missing secondary diagnoses in histopathologic sections and alerts pathologists and dermatologists to the possibility of coinfection in high-risk patients by 2 virally-mediated skin conditions. C1 [Nazarian, Rosalynn M.; Gimbel, Devon C.; Sohani, Aliyah R.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, Boston, MA 02114 USA. [Busarla, Satya Vara Prasad] Aga Khan Hosp, Dept Pathol, Kisumu, Kenya. [Sayed, Shahin; Moloo, Zahir] Aga Khan Univ Hosp, Dept Pathol, Nairobi, Kenya. [Nazarian, Rosalynn M.; Gimbel, Devon C.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dermatopathol Unit, Boston, MA 02114 USA. [Nazarian, Rosalynn M.; Gimbel, Devon C.; Sohani, Aliyah R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sohani, AR (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM arsohani@partners.org OI Sayed, Shahin/0000-0002-3472-511X; Nazarian, Rosalynn/0000-0003-4003-7193 NR 12 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD FEB PY 2012 VL 34 IS 1 BP E7 EP E9 DI 10.1097/DAD.0b013e31822438c6 PG 3 WC Dermatology SC Dermatology GA 879JQ UT WOS:000299325900002 ER PT J AU Rogers, RK Sakhuja, R Margey, R Stone, JH Rosenfield, K Jaff, MR AF Rogers, R. Kevin Sakhuja, Rahul Margey, Ronan Stone, John H. Rosenfield, Kenneth Jaff, Michael R. TI Transient Ischemic Attacks in a 22-Year-Old SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID TAKAYASU-ARTERITIS; MACARONI SIGN; THERAPY; DISEASE; CRITERIA; ULTRASONOGRAPHY; CLASSIFICATION; DIAGNOSIS C1 [Rogers, R. Kevin; Sakhuja, Rahul; Margey, Ronan; Rosenfield, Kenneth; Jaff, Michael R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med,Sect Vasc Med, Boston, MA 02114 USA. [Stone, John H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol,Dept Med, Boston, MA 02114 USA. RP Rogers, RK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med,Sect Vasc Med, 55 Fruit St,GRB8-852K, Boston, MA 02114 USA. EM R.Kevin.Rogers@gmail.com NR 35 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD FEB PY 2012 VL 125 IS 2 BP 148 EP 154 DI 10.1016/j.amjmed.2011.08.003 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 881ZU UT WOS:000299531700017 PM 22269617 ER PT J AU Jeschke, MG Finnerty, CC Herndon, DN Song, J Boehning, D Tompkins, RG Baker, HV Gauglitz, GG AF Jeschke, Marc G. Finnerty, Celeste C. Herndon, David N. Song, Juquan Boehning, Darren Tompkins, Ronald G. Baker, Henry V. Gauglitz, Gerd G. TI Severe Injury Is Associated With Insulin Resistance, Endoplasmic Reticulum Stress Response, and Unfolded Protein Response SO ANNALS OF SURGERY LA English DT Article ID SEVERE BURN INJURY; ER STRESS; HYPERMETABOLIC RESPONSE; GLUCOSE-HOMEOSTASIS; THERMAL-INJURY; HYPERGLYCEMIA; METABOLISM; CATABOLISM; APOPTOSIS; KINETICS AB Objective: We determined whether postburn hyperglycemia and insulin resistance are associated with endoplasmic reticulum (ER) stress/unfolded protein response (UPR) activation leading to impaired insulin receptor signaling. Background: Inflammation and cellular stress, hallmarks of severely burned and critically ill patients, have been causally linked to insulin resistance in type 2 diabetes via induction of ER stress and the UPR. Methods: Twenty severely burned pediatric patients were compared with 36 nonburned children. Clinical markers, protein, and GeneChip analysis were used to identify transcriptional changes in ER stress and UPR and insulin resistance-related signaling cascades in peripheral blood leukocytes, fat, and muscle at admission and up to 466 days postburn. Results: Burn-induced inflammatory and stress responses are accompanied by profound insulin resistance and hyperglycemia. Genomic and protein analysis revealed that burn injury was associated with alterations in the signaling pathways that affect insulin resistance, ER/sarcoplasmic reticulum stress, inflammation, and cell growth/apoptosis up to 466 days postburn. Conclusion: Burn-induced insulin resistance is associated with persistent ER/sarcoplasmic reticulum stress/UPR and subsequent suppressed insulin receptor signaling over a prolonged period of time. (Ann Surg 2012; 255: 370-378) C1 [Jeschke, Marc G.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Ross Tilley Burn Ctr, Div Plast Surg,Dept Surg,Sunnybrook Res Inst, Toronto, ON M4N 3M5, Canada. [Finnerty, Celeste C.; Herndon, David N.; Song, Juquan; Gauglitz, Gerd G.] Shriners Hosp Children, Galveston, TX 77550 USA. [Finnerty, Celeste C.; Herndon, David N.; Song, Juquan] Univ Texas Med Branch, Dept Surg, Galveston, TX USA. [Boehning, Darren] Univ Texas Med Branch, Dept Neurosci & Cell Biol, Galveston, TX USA. [Tompkins, Ronald G.] Shriners Hosp Children, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. [Tompkins, Ronald G.] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. [Baker, Henry V.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA. [Gauglitz, Gerd G.] Univ Munich, Dept Dermatol & Allergol, Munich, Germany. RP Jeschke, MG (reprint author), Univ Toronto, Sunnybrook Hlth Sci Ctr, Ross Tilley Burn Ctr, Div Plast Surg,Dept Surg,Sunnybrook Res Inst, 2075 Bayview Ave,Room D704, Toronto, ON M4N 3M5, Canada. EM Marc.Jeschke@sunnybrook.ca RI Boehning, Darren/I-8539-2015; OI Boehning, Darren/0000-0001-7920-6922; Baker, Henry/0000-0002-8273-5320 FU American Surgical Association Foundation; Shriners Hospitals for Children [8507, 8660, 8640, 8740, 9145]; National Institute of General Medical Sciences [R01-GM56687, T32-GM008256, P50-GM60338, U54 GM-62119-04, 2-U54-GM062119]; National Institute on Disability and Rehabilitation Research [H133A020102]; Institute for Translational Sciences Career Development Fellowship; [1KL2RR029875] FX Supported by the American Surgical Association Foundation, Shriners Hospitals for Children grants (8507, 8660, 8640, 8740, and 9145), National Institute of General Medical Sciences (R01-GM56687, T32-GM008256, P50-GM60338, and U54 GM-62119-04), and National Institute on Disability and Rehabilitation Research (H133A020102). C. C. F. is supported in part by an Institute for Translational Sciences Career Development Fellowship and 1KL2RR029875. Supported by Inflammation and the Host Response to Injury Large-Scale Collaborative Project Award 2-U54-GM062119 from the National Institute of General Medical Sciences. The Inflammation and the Host Response to Injury "Glue Grant" program is supported by the National Institute of General Medical Sciences. NR 30 TC 37 Z9 40 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD FEB PY 2012 VL 255 IS 2 BP 370 EP 378 DI 10.1097/SLA.0b013e31823e76e7 PG 9 WC Surgery SC Surgery GA 877GS UT WOS:000299166100026 PM 22241293 ER PT J AU Zakka, LR Fradkov, E Keskin, DB Tabansky, I Stern, JNH Ahmed, AR AF Zakka, L. R. Fradkov, E. Keskin, D. B. Tabansky, I. Stern, J. N. H. Ahmed, A. R. TI The role of natural killer cells in autoimmune blistering diseases SO AUTOIMMUNITY LA English DT Article DE Natural killer cells; natural killer T cells; pemphigus vulgaris; autoimmune blistering diseases; major histocompatibility complex ID MHC-CLASS-I; HUMAN NK CELLS; T-REGULATORY-CELLS; PEMPHIGUS-VULGARIS; ADAPTIVE IMMUNITY; HAIR FOLLICLE; DENDRITIC CELLS; ALOPECIA-AREATA; SELF-TOLERANCE; INHIBITORY RECEPTORS AB The major focus of this paper is to describe and evaluate current information on the role of natural killer cells (NK cells) in the pathogenesis of blistering diseases. Until now, only pemphigus vulgaris (PV) has been studied. One co-culture study demonstrated that CD4(+) T cells from the peripheral blood or perilesional skin of patients with active disease proliferate and secrete cytokines in the presence of major histocompatibility class II-expressing NK cells loaded with antigenic desmoglein self-peptides. Another study showed that NK cells can contribute to a T helper type 2-biased immune response through impaired interleukins (IL)-12 signaling and upregulation of IL, IL-10 and IL-5. Although significant data on other blistering diseases are unavailable at present, some studies implicate NK cells in disease progression. For instance, information on the role of NK cells in psoriasis and their production of tumor necrosis factor-alpha (TNF-alpha) will be provided since several TNF-alpha-inhibitors are used in its treatment. Studies on alopecia areata are also included in this paper because NK cells seem to play a key role in its pathogenesis. This review highlights the potential importance of NK cells and NKT cells as members of the large repertoire of cells and soluble mediators that play a critical role in pathogenesis of blistering diseases and other autoimmune diseases involving the skin. Therefore, the authors advocate a greater focus and interest on the study of the interaction of NK cells and the skin. C1 [Zakka, L. R.; Ahmed, A. R.] Ctr Blistering Dis, Boston, MA 02120 USA. [Keskin, D. B.; Stern, J. N. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. [Keskin, D. B.; Stern, J. N. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. [Fradkov, E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Tabansky, I.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Ahmed, AR (reprint author), Ctr Blistering Dis, 70 Parker Hill Ave, Boston, MA 02120 USA. EM arahmedmd@msn.com OI Stern, Joel N.H./0000-0002-1259-2256 NR 93 TC 10 Z9 11 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PD FEB PY 2012 VL 45 IS 1 BP 44 EP 54 DI 10.3109/08916934.2011.606446 PG 11 WC Immunology SC Immunology GA 882IT UT WOS:000299557800004 PM 21923616 ER PT J AU Punglia, RS Burstein, HJ Weeks, JC AF Punglia, Rinaa S. Burstein, Harold J. Weeks, Jane C. TI Radiation therapy for ductal carcinoma in situ SO CANCER LA English DT Article DE breast cancer; ductal carcinoma in situ; radiation therapy; decision analysis ID SURGICAL ADJUVANT BREAST; NUYS PROGNOSTIC INDEX; RANDOMIZED CONTROLLED-TRIAL; CONSERVING SURGERY; LOCAL RECURRENCE; WIDE EXCISION; CANCER; WOMEN; RADIOTHERAPY; PRESERVATION AB BACKGROUND: The benefit of adding radiation therapy after excision of ductal carcinoma in situ (DCIS) is widely debated. Randomized clinical trials are underpowered to delineate long-term outcomes after radiation. METHODS: The authors of this report constructed a Markov decision model to simulate the clinical course of DCIS in a woman aged 60 years who received treatment with either of 2 breast-conserving strategies: excision alone or excision plus radiation therapy. Sensitivity analyses were used to study the influence of risk of local recurrence, likelihood of invasive disease at recurrence, surgical choice at recurrence, and patient age at diagnosis on treatment outcomes. RESULTS: The addition of radiation therapy was associated with slight improvements in invasive disease-free and overall survival. However, radiation therapy decreased the chance of having both breasts intact over a patient's lifetime. Radiation therapy improved survival by 2.1 months for women who were diagnosed with DCIS at age 60 years but decreased the chance of having both breasts by 8.6% relative to excision alone. The differences in outcomes between the treatment strategies became smaller with increasing age at diagnosis. Sensitivity analyses revealed a greater benefit for radiation with an increased likelihood of invasive recurrence. The decrement in breast preservation with radiation therapy was mitigated by an increased likelihood of mastectomy at the time of recurrence or new breast cancer diagnosis. CONCLUSIONS: The current analysis quantified the benefits of radiation after excision of DCIS but also revealed that radiation therapy may increase the likelihood of eventual mastectomy. Therefore, the authors concluded that patient age and preferences should be considered when making the decision to add or forgo radiation for DCIS. Cancer 2012; 118: 603-11. (C) 2011 American Cancer Society. C1 [Punglia, Rinaa S.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Radiat Oncol, Boston, MA 02115 USA. [Burstein, Harold J.; Weeks, Jane C.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Med Oncol, Boston, MA 02115 USA. RP Punglia, RS (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Radiat Oncol, 44 Binney St,Smith 274, Boston, MA 02115 USA. EM rpunglia@lroc.harvard.edu FU National Institutes of Health [1K07 CA118269] FX This research was supported by a Career Development Award from the National Institutes of Health (1K07 CA118269 to R. S. P.). NR 30 TC 8 Z9 8 U1 0 U2 1 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 FEB 1 PY 2012 VL 118 IS 3 BP 603 EP 611 DI 10.1002/cncr.26293 PG 9 WC Oncology SC Oncology GA 879NB UT WOS:000299335500005 PM 21720992 ER PT J AU von Mehren, M Rankin, C Goldblum, JR Demetri, GD Bramwell, V Ryan, CW Borden, E AF von Mehren, Margaret Rankin, Cathryn Goldblum, John R. Demetri, George D. Bramwell, Vivien Ryan, Christopher W. Borden, Ernest TI Phase 2 Southwest Oncology Group-directed intergroup trial (S0505) of sorafenib in advanced soft tissue sarcomas SO CANCER LA English DT Article DE tyrosine kinase inhibitor; liposarcoma; leiomyosarcoma; angiosarcoma; solitary fibrous tumor ID ENDOTHELIAL GROWTH-FACTOR; FACTOR RECEPTOR; BETA-SUBUNIT; TUMORS; EXPRESSION; HEMANGIOPERICYTOMA; SUNITINIB; DISEASE; KINASE; GRADE AB BACKGROUND: Patients with advanced soft tissue sarcomas (STS) have limited therapeutic options. Sorafenib (BAY 43-9006) is a multitargeted tyrosine kinase inhibitor of raf, vascular endothelial growth factor receptors 1 (VEGFR1) through 3, platelet-derived growth factor B, fms-like tyrosine kinase 3, and c-kit, and some of these may be relevant in STS. METHODS: The authors tested sorafenib at a dose of 400 mg twice daily in patients with advanced vascular sarcoma (VS), high-grade liposarcomas, and leiomyosarcomas who had received 0 or 1 previous regimens for advanced disease. RESULTS: Fifty-one patients were accrued to the study, and 37 were evaluable for toxicity and response. There were no unexpected side effects and no confirmed responses. The median progression-free survival was 3 months, and the median overall survival was 17 months. Six of 8 patients in the VS cohort had prolonged clinical benefit (stable disease or better), resulting in a median progression-free survival of 5 months compared with 2 to 3 months for the patients who had liposarcoma and leiomyosarcomas. CONCLUSIONS: Sorafenib at the dose and schedule studied did not result in any responses in the VS, liposarcoma, or leiomyosarcoma cohort according to Response Evaluation Criteria in Solid Tumors. Cancer 2012; 118: 770-6. (C) 2011 American Cancer Society. C1 [von Mehren, Margaret] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Rankin, Cathryn] SW Oncol Grp, Ctr Stat, Seattle, WA USA. [Goldblum, John R.] Cleveland Clin Fdn, Dept Pathol, Cleveland, OH 44195 USA. [Borden, Ernest] Cleveland Clin Fdn, Dept Med Oncol, Cleveland, OH 44195 USA. [Demetri, George D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Demetri, George D.] Canc & Leukemia Grp B, Chicago, IL USA. [Bramwell, Vivien] Univ Calgary, Tom Baker Canc Ctr, Dept Med Oncol, Calgary, AB, Canada. [Bramwell, Vivien] Queens Univ, Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. [Ryan, Christopher W.] Oregon Hlth & Sci Univ, Dept Med Oncol, Portland, OR 97201 USA. RP von Mehren, M (reprint author), Fox Chase Canc Ctr, Dept Med Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM margaret.vonMehren@fccc.edu FU National Cancer Institute, Department of Health and Human Services [CA32102, CA38926, CA46113, CA20319, CA68183, CA46368, CA35431, CA45807, CA04919, CA35090, CA35178, CA35176, CA45560, CA45808, CA37981, CA46136, CA14028, CA46441, CA58861, CA12644, CA77202, CCSRI 021039, CA031946] FX This investigation was supported in part by the following Public Health Service Cooperative Agreement grant numbers awarded by the National Cancer Institute, Department of Health and Human Services: CA32102, CA38926, CA46113, CA20319, CA68183, CA46368, CA35431, CA45807, CA04919, CA35090, CA35178, CA35176, CA45560, CA45808, CA37981, CA46136, CA14028, CA46441, CA58861, and CA12644 (to Southwest Oncology Group); CA77202 and CCSRI 021039 (to the National Cancer Institute of Canada Clinical Trials Group); and CA031946 (to Cancer and Leukemia Group B). NR 25 TC 47 Z9 48 U1 0 U2 0 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 FEB 1 PY 2012 VL 118 IS 3 BP 770 EP 776 DI 10.1002/cncr.26334 PG 7 WC Oncology SC Oncology GA 879NB UT WOS:000299335500022 PM 21751200 ER PT J AU Liu, W Choueiri, TK Cho, E AF Liu, Wei Choueiri, Toni K. Cho, Eunyoung TI Statin use and the risk of renal cell carcinoma in 2 prospective US cohorts SO CANCER LA English DT Article DE carcinoma; renal cell; neoplasms; statin; prospective studies ID CANCER; SIMVASTATIN; MEN; DATABASE; DISEASE; DRUGS; WOMEN; TRIAL AB BACKGROUND: Statins are widely used cholesterol-lowering agents that may have potential antitumor effect. Epidemiological studies on statin use and renal cell carcinoma (RCC) risk have been inconsistent. METHODS: The authors investigated the association between statin use and RCC risk in the Nurses' Health Study and Health Professionals Follow-Up Study. In total, 80,782 women and 37,869 men were followed for 14 years and 16 years, respectively. Regular statin use was assessed at baseline and was updated biennially during follow-up. RCC diagnosis was confirmed by medical record review. RESULTS: Two hundred seventy-seven incident RCC cases (164 women and 113 men) were identified. Compared with no current use, the multivariate relative risks of current statin use were 0.68 (95% confidence interval, 0.46-1.00) in women and 1.17 (95% confidence interval, 0.75-1.82) in men. The results for ever versus never users of statins were similar. No dose-response relation with duration of statin use and RCC risk was observed. On subgroup analyses, statin use was associated with a reduced RCC risk among women who had no history of hypertension. CONCLUSIONS: The current study indicated that statin use may be associated with a lower risk of RCC in women, although these results need to be investigated further. Cancer 2012; 118: 797-803. (C) 2011 American Cancer Society. C1 [Liu, Wei; Cho, Eunyoung] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Liu, Wei; Cho, Eunyoung] Harvard Univ, Sch Med, Boston, MA USA. [Liu, Wei] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. [Cho, Eunyoung] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Cho, E (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM eunyoung.cho@channing.harvard.edu FU National Institute of Health [CA137764, CA87969, CA55075] FX This study was supported by research grant CA137764, CA87969, and CA55075 from the National Institute of Health. NR 32 TC 12 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2012 VL 118 IS 3 BP 797 EP 803 DI 10.1002/cncr.26338 PG 7 WC Oncology SC Oncology GA 879NB UT WOS:000299335500025 PM 21751202 ER PT J AU Zhai, RH Zhao, Y Liu, G Ter-Minassian, M Wu, IC Wang, ZX Su, L Asomaning, K Chen, F Kulke, MH Lin, XH Heist, RS Wain, JC Christiani, DC AF Zhai, Rihong Zhao, Yang Liu, Geoffrey Ter-Minassian, Monica Wu, I. -Chen Wang, Zhaoxi Su, Li Asomaning, Kofi Chen, Feng Kulke, Matthew H. Lin, Xihong Heist, Rebecca S. Wain, John C. Christiani, David C. TI Interactions between environmental factors and polymorphisms in angiogenesis pathway genes in esophageal adenocarcinoma risk: A case-only study SO CANCER LA English DT Article DE esophageal adenocarcinoma; angiogenesis pathway genes; gene-environment interaction; case-only analysis ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; CIGARETTE-SMOKING; BREAST-CANCER; BARRETTS-ESOPHAGUS; COLORECTAL-CANCER; RANDOM FORESTS; TUMOR-GROWTH; SAMPLE-SIZE; ASSOCIATION AB BACKGROUND: Gastroesophageal reflux disease (GERD), higher body mass index (BMI), smoking, and genetic variants in angiogenic pathway genes have been individually associated with increased risk of esophageal adenocarcinoma. However, how angiogenic gene polymorphisms and environmental factors jointly affect esophageal adenocarcinoma development remains unclear. METHODS: By using a case-only design (n = 335), the authors examined interactions between 141 functional/tagging angiogenic single nucleotide polymorphisms (SNPs) and environmental factors (GERD, BMI, smoking) in modulating esophageal adenocarcinoma risk. Gene-environment interactions were assessed by a 2-step approach. First, the authors applied random forest to screen for important SNPs that had either main or interaction effects. Second, they used case-only logistic regression to assess the effects of geneenvironment interactions on esophageal adenocarcinoma risk, adjusting for covariates and false-discovery rate. RESULTS: Random forest analyses identified 3 sets of SNPs (17 SNPs-GERD, 26 SNPs-smoking, and 34 SNPs-BMI) that had the highest importance scores. In subsequent logistic regression analyses, interactions between 2 SNPs (rs2295778 of HIF1AN, rs13337626 of TSC2) and GERD, 2 SNPs (rs2295778 of HIF1AN, rs2296188 of VEGFR1) and smoking, and 7 SNPs (rs2114039 of PDGRFA, rs2296188 of VEGFR1, rs11941492 of VEGFR1, rs17708574 of PDGFRB, rs7324547 of VEGFR1, rs17619601 of VEGFR1, and rs17625898 of VEGFR1) and BMI were significantly associated with esophageal adenocarcinoma development (all false-discovery rates <= 0.10). Moreover, these interactions tended to have SNP dose-response effects for increased esophageal adenocarcinoma risk with increasing number of combined risk genotypes. CONCLUSIONS: These findings suggest that genetic variations in angiogenic genes may modify esophageal adenocarcinoma susceptibility through interactions with environmental factors in an SNP dose-response manner. Cancer 2012; 118: 804-11. (C) 2011 American Cancer Society. C1 [Zhai, Rihong; Zhao, Yang; Ter-Minassian, Monica; Wu, I. -Chen; Wang, Zhaoxi; Su, Li; Asomaning, Kofi; Chen, Feng; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Liu, Geoffrey] Univ Toronto, Ontario Canc Inst, Princess Margaret Hosp, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Wu, I. -Chen] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Internal Med, Div Gastroenterol, Kaohsiung, Taiwan. [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Heist, Rebecca S.; Wain, John C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM rzhai@hsph.harvard.edu; dchris@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU National Institute of Health [CA92824, CA74386, CA90578, CA119650]; Flight Attendant Medical Research Institute [062459_YCSA]; Kevin Jackson Memorial Fund; Alan Brown Chair of Molecular Genomics FX Supported by National Institute of Health grants CA92824, CA74386, CA90578, and CA119650 (D. C. C.); Flight Attendant Medical Research Institute grant 062459_YCSA (R.Z.); and Kevin Jackson Memorial Fund and Alan Brown Chair of Molecular Genomics (G.L.). NR 54 TC 6 Z9 7 U1 4 U2 7 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 FEB 1 PY 2012 VL 118 IS 3 BP 804 EP 811 DI 10.1002/cncr.26325 PG 8 WC Oncology SC Oncology GA 879NB UT WOS:000299335500026 PM 21751195 ER PT J AU Freedman, RA Keating, NL AF Freedman, Rachel A. Keating, Nancy L. TI Receipt of adjuvant breast cancer therapy in minority women SO CANCER LA English DT Letter C1 [Freedman, Rachel A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 FEB 1 PY 2012 VL 118 IS 3 BP 864 EP 865 DI 10.1002/cncr.26326 PG 2 WC Oncology SC Oncology GA 879NB UT WOS:000299335500034 ER PT J AU Spellberg, B Lipsky, BA AF Spellberg, Brad Lipsky, Benjamin A. TI Systemic Antibiotic Therapy for Chronic Osteomyelitis in Adults SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; GRAM-NEGATIVE BACILLI; INFECTED ORTHOPEDIC IMPLANTS; MULTIPLE-DOSE PHARMACOKINETICS; PROSTHETIC JOINT INFECTIONS; ORAL CIPROFLOXACIN THERAPY; DIABETIC FOOT INFECTIONS; SOFT-TISSUE INFECTIONS; TRIMETHOPRIM-SULFAMETHOXAZOLE; PSEUDOMONAS-AERUGINOSA AB The standard recommendation for treating chronic osteomyelitis is 6 weeks of parenteral antibiotic therapy. However, oral antibiotics are available that achieve adequate levels in bone, and there are now more published studies of oral than parenteral antibiotic therapy for patients with chronic osteomyelitis. Oral and parenteral therapies achieve similar cure rates; however, oral therapy avoids risks associated with intravenous catheters and is generally less expensive, making it a reasonable choice for osteomyelitis caused by susceptible organisms. Addition of adjunctive rifampin to other antibiotics may improve cure rates. The optimal duration of therapy for chronic osteomyelitis remains uncertain. There is no evidence that antibiotic therapy for >4-6 weeks improves outcomes compared with shorter regimens. In view of concerns about encouraging antibiotic resistance to unnecessarily prolonged treatment, defining the optimal route and duration of antibiotic therapy and the role of surgical debridement in treating chronic osteomyelitis are important, unmet needs. C1 [Spellberg, Brad] Harbor UCLA Med Ctr, Div Gen Internal Med, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Spellberg, Brad] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lipsky, Benjamin A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Lipsky, Benjamin A.] Univ Washington, Seattle, WA 98195 USA. RP Spellberg, B (reprint author), Harbor UCLA Med Ctr, Div Gen Internal Med, Los Angeles Biomed Res Inst, 1124 W Carson St,Liu Vaccine Bldg, Torrance, CA 90502 USA. EM bspellberg@labiomed.org OI Lipsky, Benjamin A./0000-0001-9886-5114 FU Gilead; Astellas; Novartis; Cubist; GlaxoSmithKline; Pfizer; Basilea; Medicines Company; Achaogen; Eisai; Meiji; Polymedix FX B. S. has received clinical trial grant/contract support from Gilead, Astellas, Novartis, and Cubist and consulting fees from GlaxoSmithKline, Pfizer, Basilea, The Medicines Company, Achaogen, Eisai, Meiji, and Polymedix. B. A. L. has received grant support or provided consultation to the following: Pfizer, Merck, Cubist, and Johnson & Johnson. NR 172 TC 63 Z9 69 U1 5 U2 15 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 FEB 1 PY 2012 VL 54 IS 3 BP 393 EP 407 DI 10.1093/cid/cir842 PG 15 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 876SM UT WOS:000299128000021 PM 22157324 ER PT J AU Triant, VA Josephson, F Rochester, CG Althoff, KN Marcus, K Munk, R Cooper, C D'Agostino, RB Costagliola, D Sabin, CA Williams, PL Hughes, S Post, WS Chandra-Strobos, N Guaraldi, G Young, SS Obenchain, R Bedimo, R Miller, V Strobos, J AF Triant, V. A. Josephson, F. Rochester, C. G. Althoff, K. N. Marcus, K. Munk, R. Cooper, C. D'Agostino, R. B. Costagliola, D. Sabin, C. A. Williams, P. L. Hughes, S. Post, W. S. Chandra-Strobos, N. Guaraldi, G. Young, S. S. Obenchain, R. Bedimo, R. Miller, V. Strobos, J. TI Adverse Outcome Analyses of Observational Data: Assessing Cardiovascular Risk in HIV Disease SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; REVERSE-TRANSCRIPTASE INHIBITORS; INDIVIDUAL ANTIRETROVIRAL DRUGS; CORONARY-HEART-DISEASE; INFECTED PATIENTS; CLINICAL-TRIALS; ABACAVIR USE; THERAPY; EVENTS; COHORT AB Clinical decisions are ideally based on randomized trials but must often rely on observational data analyses, which are less straightforward and more influenced by methodology. The authors, from a series of expert roundtables convened by the Forum for Collaborative HIV Research on the use of observational studies to assess cardiovascular disease risk in human immunodeficiency virus infection, recommend that clinicians who review or interpret epidemiological publications consider 7 key statistical issues: (1) clear explanation of confounding and adjustment; (2) handling and impact of missing data; (3) consistency and clinical relevance of outcome measurements and covariate risk factors; (4) multivariate modeling techniques including timedependent variables; (5) how multiple testing is addressed; (6) distinction between statistical and clinical significance; and (7) need for confirmation from independent databases. Recommendations to permit better understanding of potential methodological limitations include both responsible public access to de-identified source data, where permitted, and exploration of novel statistical methods. C1 [Miller, V.; Strobos, J.] Univ Calif Berkeley, Berkeley Sch Publ Hlth, Washington, DC 20036 USA. [Triant, V. A.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Josephson, F.] Med Prod Agcy, Uppsala, Sweden. [Rochester, C. G.; Marcus, K.; Cooper, C.] US FDA, Silver Spring, MD USA. [Althoff, K. N.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Munk, R.] Univ New Mexico, Sch Med, Dept Internal Med, Div Infect Dis, Albuquerque, NM 87131 USA. [D'Agostino, R. B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Costagliola, D.] Univ Paris 06, UMR S 943, Paris, France. [Costagliola, D.] INSERM, UMR S 943, Paris, France. [Costagliola, D.] AP HP, Paris, France. [Costagliola, D.] Hop La Pitie Salpetriere, Serv Malad Infect & Trop, Paris, France. [Sabin, C. A.] UCL, Res Dept Infect & Populat Hlth, Sch Med, London WC1E 6BT, England. [Williams, P. L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hughes, S.] GlaxoSmithKline Inc, Dept Stat, Brentford, Middx, England. [Post, W. S.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Chandra-Strobos, N.] Johns Hopkins Bayview Med Ctr, Dept Med, Div Cardiol, Baltimore, MD USA. [Guaraldi, G.] Univ Modena & Reggio Emilia, Dept Med & Med Specialties, Modena, Italy. [Young, S. S.] Natl Inst Stat Sci, Res Triangle Pk, NC USA. [Obenchain, R.] Risk Benefit Stat LLC, Carmel, IA USA. [Bedimo, R.] Univ Texas SW Med Ctr Dallas, VA N Texas Healthcare Syst, Dallas, TX 75390 USA. [Bedimo, R.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Infect Dis, Dallas, TX 75390 USA. [Strobos, J.] Forum Collaborat HIV Res, Washington, DC USA. RP Strobos, J (reprint author), Univ Calif Berkeley, Berkeley Sch Publ Hlth, 1608 Rhode Isl Ave NW, Washington, DC 20036 USA. EM jur@berkeley.edu RI Costagliola, Dominique/H-5849-2011; OI Costagliola, Dominique/0000-0003-0765-0869; Obenchain, Robert/0000-0002-8395-1666; Guaraldi, Giovanni/0000-0002-5724-3914 FU Forum for Collaborative HIV Research; HAART Oversight Committee; Gilead Sciences; Abbott Laboratories; ViiV Healthcare; Tibotec Therapeutics; Bill and Melinda Gates Foundation; AmfAR; National Institutes of Health; Centers for Disease Control and Prevention; Bristol-Myers Squibb; BD Bio-sciences; bioMerieux; Boehringer Ingelheim Pharmaceuticals; Idenix Pharmaceuticals; Merck Research Laboratories; Monogram Biosciences; Roche Molecular Diagnostics; EMD Serono; Centocor Ortho Biotech; Merck Co.; Abbott; Boehringer-Ingelheim; GlaxoSmithKline; Janssen-Cilag; Merck Sharp Dohme-Chibret; Roche Pharmaceuticals; Janssen Pharmaceuticals FX Support for the series of expert roundtable discussions, at which the need for this article was identified, was graciously provided by the Forum for Collaborative HIV Research, the HAART Oversight Committee, Gilead Sciences, Abbott Laboratories, ViiV Healthcare, and Tibotec Therapeutics. The Forum's HIV activities are supported by the Bill and Melinda Gates Foundation, AmfAR, the National Institutes of Health, the Centers for Disease Control and Prevention, Gilead Sciences, Abbott Laboratories, ViiV Healthcare, Bristol-Myers Squibb, BD Bio-sciences, bioMerieux, Boehringer Ingelheim Pharmaceuticals, Idenix Pharmaceuticals, Merck Research Laboratories, Monogram Biosciences, Roche Molecular Diagnostics, EMD Serono, and Centocor Ortho Biotech.; R. B. receives financial support to provide scientific advice to Merck and Co, Tibotec Therapeutics, Gilead Sciences, EMD Serono, and Abbott and receives research funding from Merck & Co. D. C. receives financial support to provide scientific advice to, and receives grants from, Abbott, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen-Cilag, Merck Sharp & Dohme-Chibret, and Roche Pharmaceuticals. S. H. is an employee of GlaxoSmithKline and holds stock options in GlaxoSmithKline. C. A. S. receives financial support for providing scientific advice to Janssen Pharmaceuticals, ViiV Healthcare, Gilead Sciences, and Bristol-Myers Squibb. V. A. T. and K. N. A. are supported by National Institutes of Health grants. C. G. R., K. M., and C. C. are employees of the US government. The views expressed in this article are their individual views and not those of the US government. F. J. is an employee of the Swedish Medical Products Agency (MPA). The views expressed in this article are his individual views, not those of the MPA. J. S. and V. M. are employees of the Forum for Collaborative HIV Research, an administrative unit in the School of Public Health of the University of California, Berkeley. All other authors report no potential conflicts of interest. NR 41 TC 8 Z9 8 U1 0 U2 4 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 FEB 1 PY 2012 VL 54 IS 3 BP 408 EP 413 DI 10.1093/cid/cir829 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 876SM UT WOS:000299128000022 PM 22095570 ER PT J AU Wiederhold, NP Najvar, LK Bocanegra, R Kirkpatrick, WR Patterson, TF AF Wiederhold, N. P. Najvar, L. K. Bocanegra, R. Kirkpatrick, W. R. Patterson, T. F. TI Comparison of anidulafungin's and fluconazole's in vivo activity in neutropenic and non-neutropenic models of invasive candidiasis SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE Anidulafungin; Candida albicans; candidiasis; fluconazole; neutropenia ID MURINE DISSEMINATED CANDIDIASIS; IMMUNE-SYSTEM; CASPOFUNGIN; ASPERGILLUS; ANTIFUNGAL; LY303366; ALBICANS; MICE AB We compared the rate and extent of anidulafungins and fluconazoles activity in neutropenic and non-neutropenic mice with Candida albicans invasive candidiasis. In immunocompetent mice, anidulafungin significantly improved survival vs. controls and fluconazole, and significant reductions in (1 -> 3)-beta-D-glucan and fungal burden were observed. In neutropenic animals, the highest doses of anidulafungin (5 mg/kg) and fluconazole (10 mg/kg) also improved survival and reduced fungal burden. However, there were no differences in survival between these antifungals as anidulafungins activity was attenuated in this model. These results demonstrate that the extent of anidulafungin in vivo efficacy may be dependent on host immune status. C1 [Wiederhold, N. P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Wiederhold, N. P.; Najvar, L. K.; Bocanegra, R.; Kirkpatrick, W. R.; Patterson, T. F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. [Najvar, L. K.; Bocanegra, R.; Kirkpatrick, W. R.; Patterson, T. F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Wiederhold, NP (reprint author), UTHSCSA, PERC MSC 6220,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM wiederholdn@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU Pfizer, Inc.; Pfizer; Schering-Plough; Merck; Basilea; Astellas FX Funding for this study was provided by Pfizer, Inc. NPW has received research support from Pfizer, Schering-Plough, Merck, Basilea and Astellas, and travel support from Viamet. He has also served as a consultant for Merck, Astellas and Viamet. TFP has received research support from Basilea, Astellas, Merck, Pfizer and Schering-Plough, and has served as a consultant for Basilea, Astellas, Merck, Pfizer, Toyama and Viamet. NR 17 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1198-743X EI 1469-0691 J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD FEB PY 2012 VL 18 IS 2 BP E20 EP E23 DI 10.1111/j.1469-0691.2011.03712.x PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 879MW UT WOS:000299335000002 PM 22128831 ER PT J AU Billings, JA AF Billings, J. Andrew TI Humane terminal extubation reconsidered: The role for preemptive analgesia and sedation SO CRITICAL CARE MEDICINE LA English DT Review DE analgesia; extubation; palliative sedation; preemptive medical ethics; terminal weaning ID INTENSIVE-CARE-UNIT; LIFE-SUSTAINING TREATMENT; MECHANICAL VENTILATION; DEATH RATTLE; OF-LIFE; PALLIATIVE SEDATION; CRITICALLY-ILL; DYING PATIENTS; CLINICAL MANAGEMENT; VEGETATIVE STATE AB Patient comfort is not assured by common practices for terminal extubation. Treatment guidelines suggest minimizing dosage of opioids and sedatives. Multiple lines of evidence indicate that clinicians are limited in their ability to recognize distress in such patients and tend to undermedicate patients in distress. Yet suffering of any significant degree should be unacceptable. For painful procedures, such as surgery, the analogous practice of postponing anesthesia until the patient evidences discomfort would never be tolerated. Waiting for signs of suffering before initiating excellent analgesia and sedation inexorably subjects patients to distress. Therefore, when death is inevitable and imminent after extubation, suffering should be anticipated, concerns about respiratory depression dismissed, and vigorous preemptive deep sedation or anesthesia provided. (Crit Care Med 2012; 40:625-630) C1 Massachusetts Gen Hosp, Cambridge, MA USA. RP Billings, JA (reprint author), Massachusetts Gen Hosp, Cambridge, MA USA. EM Jbillings@partners.org NR 112 TC 21 Z9 22 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2012 VL 40 IS 2 BP 625 EP 630 DI 10.1097/CCM.0b013e318228235d PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 879EW UT WOS:000299313500035 PM 21765350 ER PT J AU Wang, JP Alston, TA AF Wang, Jingping Alston, Theodore A. TI Gallic treatment is galling to Pseudomonas SO CRITICAL CARE MEDICINE LA English DT Editorial Material ID ACID C1 [Wang, Jingping; Alston, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. RP Wang, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. NR 11 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2012 VL 40 IS 2 BP 690 EP 691 DI 10.1097/CCM.0b013e318236e986 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 879EW UT WOS:000299313500064 PM 22249056 ER PT J AU Halperin, F Lopez, X Manning, R Kahn, CR Kullcarni, RN Goldfine, AB AF Halperin, Florencia Lopez, Ximena Manning, Raquel Kahn, C. Ronald Kullcarni, Rohit N. Goldfine, Allison B. TI Insulin Augmentation of Glucose-Stimulated Insulin Secretion Is Impaired in Insulin-Resistant Humans SO DIABETES LA English DT Article ID PANCREATIC BETA-CELLS; FEEDBACK INHIBITION; EXOGENOUS INSULIN; PHOSPHATIDYLINOSITOL 3-KINASE; GLUCAGON-SECRETION; DIABETES-MELLITUS; GENE-EXPRESSION; HEALTHY HUMANS; HUMAN ISLETS; RECEPTOR AB Type 2 diabetes (T2D) is characterized by insulin resistance and pancreatic beta-cell dysfunction, the latter possibly caused by a defect in insulin signaling in beta-cells. We hypothesized that insulin's effect to potentiate glucose-stimulated insulin secretion (GSIS) would be diminished in insulin-resistant persons. To evaluate the effect of insulin to modulate GSIS in insulin-resistant compared with insulin-sensitive subjects, 10 participants with impaired glucose tolerance (IGT), 11 with T2D, and 8 healthy control subjects were studied on two occasions. The insulin secretory response was assessed by the administration of dextrose for 80 min following a 4-h clamp with either saline infusion (sham) or an isoglycemic-hyperinsuilinemic clamp using B28-Asp-insulin (which can be distinguished immunologically from endogenous insulin) that raised insulin concentrations to high physiologic concentrations. Pre-exposure to insulin augmented GSIS in healthy persons. This effect was attenuated in insulin-resistant cohorts, both those with IGT and those with T2D. Insulin potentiates glucose-stimulated insulin secretion in insulin-resistant subjects to a lesser degree than in normal subjects. This is consistent with an effect of insulin to regulate beta-cell function in humans in vivo with therapeutic implications. Diabetes 61:301-309, 2012 C1 [Halperin, Florencia; Lopez, Ximena; Manning, Raquel; Kahn, C. Ronald; Kullcarni, Rohit N.; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Halperin, Florencia; Lopez, Ximena; Goldfine, Allison B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Halperin, Florencia; Kahn, C. Ronald; Kullcarni, Rohit N.; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA. [Lopez, Ximena] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU American Diabetes Association [06-CD-07]; National Institutes of Health [R01 DK070648, R01 DK070648-03S, R01 DK067536, R01 DK31036]; Joslin Diabetes and Endocrinology Research Center [P30-DK36836]; General Clinical Research Center [M01-RR001032] FX This work was supported by funding sources including the American Diabetes Association 06-CD-07 (to A.B.G.); National Institutes of Health R01 DK070648 (to A.B.G.), R01 DK070648-03S (to X.L.), R01 DK067536 (to R.N.K), R01 DK31036 (to C.R.K.); and Joslin Diabetes and Endocrinology Research Center P30-DK36836 and General Clinical Research Center M01-RR001032. NR 49 TC 25 Z9 26 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2012 VL 61 IS 2 BP 301 EP 309 DI 10.2337/db11-1067 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 885RI UT WOS:000299798100007 PM 22275085 ER PT J AU Lau, GJ Godin, N Maachi, H Lo, CS Wu, SJ Zhu, JX Brezniceanu, ML Chenier, I Fragasso-Marquis, J Lattouf, JB Ethier, J Filep, JG Ingelfinger, JR Nair, V Kretzler, M Cohen, CD Zhang, SL Chan, JSD AF Lau, Garnet J. Godin, Nicolas Maachi, Hasna Lo, Chao-Sheng Wu, Shyh-Jong Zhu, Jian-Xin Brezniceanu, Marie-Luise Chenier, Isabelle Fragasso-Marquis, Joelle Lattouf, Jean-Baptiste Ethier, Jean Filep, Janos G. Ingelfinger, Julie R. Nair, Viji Kretzler, Matthias Cohen, Clemens D. Zhang, Shao-Ling Chan, John S. D. TI Bcl-2-Modifying Factor Induces Renal Proximal Tubular Cell Apoptosis in Diabetic Mice SO DIABETES LA English DT Article ID ANGIOTENSINOGEN GENE-EXPRESSION; GLOMERULOTUBULAR JUNCTION ABNORMALITIES; RAT-KIDNEY; ATUBULAR GLOMERULI; TRANSGENIC MICE; NEPHROPATHY; INJURY; BMF; OVEREXPRESSION; ACTIVATION AB This study investigated the mechanisms underlying tubular apoptosis in diabetes by identifying proapoptotic genes that are differentially upregulated by reactive oxygen species in renal proximal tubular cells (RFTCs) in models of diabetes. Total RNAs isolated from renal proximal tubules (RPTs) of 20-week-old heterozygous db/m+, db/db, and db/db catalase (CAT)-transgenic (Tg) mice were used for DNA chip microarray analysis. Real-time quantitative PCR assays, immunohistochemistry, and mice rendered diabetic with streptozotocin were used to validate the proapoptotic gene expression in RPTs. Cultured rat RFTCs were used to confirm the apoptotic activity and regulation of proapoptotic gene expression. Additionally, studies in kidney tissues from patients with and without diabetes were used to confirm enhanced proapoptotic gene expression in RPTs. Bcl-2-modifying factor (Bmf) was differentially upregulated (P < 0.01) in RFTs of db/db mice compared with db/m+ and dbldb CAT-Tg mice and in RPTs of streptozotocin-induced diabetic mice in which insulin reversed this finding. In vitro, Bmf cDNA overexpression in rat RPTCs coimmunoprecipated with Bcl-2, enhanced caspase-3 activity, and promoted apoptosis. High glucose (25 mmol/L) induced Bmf mRNA expression in RPTCs, whereas rotenone, catalase, diphenylene iodinium, and apocynin decreased it. Knockdown of Bmf' with small interfering RNA reduced high glucose induced apoptosis in RFTCs. More important, enhanced Bmf expression was detected in RFTs of kidneys from patients with diabetes. These data demonstrate differential upregulation of Bmf in diabetic RPTs and suggest a potential role for Bmf in regulating RPTC apoptosis and tubular atrophy in diabetes. Diabetes 61:474-484, 2012 C1 [Lau, Garnet J.; Godin, Nicolas; Maachi, Hasna; Lo, Chao-Sheng; Wu, Shyh-Jong; Zhu, Jian-Xin; Brezniceanu, Marie-Luise; Chenier, Isabelle; Fragasso-Marquis, Joelle; Lattouf, Jean-Baptiste; Ethier, Jean; Zhang, Shao-Ling; Chan, John S. D.] Univ Montreal, Hotel Dieu Hosp, CRCHUM, Montreal, PQ, Canada. [Filep, Janos G.] Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ, Canada. [Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. [Nair, Viji; Kretzler, Matthias] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Cohen, Clemens D.] Univ Zurich, Inst Physiol, Univ Zurich Hosp, Div Nephrol, Zurich, Switzerland. RP Chan, JSD (reprint author), Univ Montreal, Hotel Dieu Hosp, CRCHUM, Montreal, PQ, Canada. EM john.chan@umontreal.ca FU Canadian Institutes of Health Research [MOP 84363, MOP 106688]; Kidney Foundation of Canada [KFOC80015]; National Institutes of Health [HL-48455]; Applied System Biology Core, O'Brien Renal Center, University of Michigan [P30 DK081943-01]; Else Kroner-Fresenius Foundation FX This work was supported, in part, by grants from the Canadian Institutes of Health Research (MOP 84363 and MOP 106688) to J.S.D.C., the Kidney Foundation of Canada (KFOC80015) to J.S.D.C., and the National Institutes of Health (HL-48455) to J.R.I. M.K. and V.N. were supported by P30 DK081943-01 (Applied System Biology Core, O'Brien Renal Center, University of Michigan), and C.D.C. was supported by the Else Kroner-Fresenius Foundation. NR 42 TC 12 Z9 14 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2012 VL 61 IS 2 BP 474 EP 484 DI 10.2337/db11-0141 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 885RI UT WOS:000299798100026 PM 22210314 ER PT J AU Peters, EJG Lipsky, BA Berendt, AR Embil, JM Lavery, LA Senneville, E Urbancic-Rovan, V Bakker, K Jeffcoate, WJ AF Peters, E. J. G. Lipsky, B. A. Berendt, A. R. Embil, J. M. Lavery, L. A. Senneville, E. Urbancic-Rovan, V. Bakker, K. Jeffcoate, W. J. TI A systematic review of the effectiveness of interventions in the management of infection in the diabetic foot SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article; Proceedings Paper CT 6th International Symposium on the Diabetic Foot CY MAY 10-14, 2011 CL Noordwijkerhout, NETHERLANDS DE diabetes mellitus; diabetic foot; infection; osteomyelitis; antibiotics; surgery; systematic review ID COLONY-STIMULATING FACTOR; SKIN-STRUCTURE INFECTIONS; RANDOMIZED-CONTROLLED-TRIAL; HYPERBARIC-OXYGEN THERAPY; SOFT-TISSUE INFECTIONS; OPEN-LABEL TRIAL; COMPLICATED SKIN; PIPERACILLIN-TAZOBACTAM; ANTIBIOTIC-THERAPY; MULTICENTER TRIAL AB The International Working Group on the Diabetic Foot expert panel on infection conducted a systematic review of the published evidence relating to treatment of foot infection in diabetes. Our search of the literature published prior to August 2010 identified 7517 articles, 29 of which fulfilled predefined criteria for detailed data extraction. Four additional eligible papers were identified from other sources. Of the total of 33 studies, 29 were randomized controlled trials, and four were cohort studies. Among 12 studies comparing different antibiotic regimens in the management of skin and soft-tissue infection, none reported a better responsewith any particular regimen. Of seven studies that compared antibiotic regimens in patients with infection involving both soft tissue and bone, one reported a better clinical outcome in those treated with cefoxitin compared with ampicillin/ sulbactam, but the others reported no differences between treatment regimens. In two health economic analyses, there was a small saving using one regimen versus another. No published data support the superiority of any particular route of delivery of systemic antibiotics or clarify the optimal duration of antibiotic therapy in either soft-tissue infection or osteomyelitis. In one non-randomized cohort study, the outcome of treatment of osteomyelitis was better when the antibiotic choice was based on culture of bone specimens as opposed to wound swabs, but this study was not randomized, and the results may have been affected by confounding factors. Results from two studies suggested that early surgical intervention was associated with a significant reduction in major amputation, but the methodological quality of both was low. In two studies, the use of superoxidized water was associated with a better outcome than soap or povidone iodine, but both had a high risk of bias. Studies using granulocyte-colony stimulating factor reported mixed results. There was no improvement in infection outcomes associated with hyperbaric oxygen therapy. No benefit has been reported with any other intervention, and, overall, there are currently no trial data to justify the adoption of any particular therapeutic approach in diabetic patients with infection of either soft tissue or bone of the foot. Copyright (C) 2012 John Wiley & Sons, Ltd. C1 [Peters, E. J. G.] Vrije Univ Amsterdam, Med Ctr, Dept Internal Med, NL-1007 MB Amsterdam, Netherlands. [Lipsky, B. A.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Berendt, A. R.] Oxford Univ Hosp NHS Trust, Oxford, England. [Embil, J. M.] Univ Manitoba, Winnipeg, MB, Canada. [Lavery, L. A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Lavery, L. A.] Parkland Hosp, Dallas, TX USA. [Senneville, E.] Gustave Dron Hosp, Tourcoing, France. [Urbancic-Rovan, V.] Univ Med Ctr, Ljubljana, Slovenia. [Bakker, K.] IWGDF, Heemstede, Netherlands. [Jeffcoate, W. J.] Nottingham Univ Hosp Trust, Nottingham, England. RP Peters, EJG (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Internal Med, Room ZH-4A35,POB 7057, NL-1007 MB Amsterdam, Netherlands. EM e.peters@vumc.nl RI Peters, Edgar /B-7790-2014; OI Lipsky, Benjamin A./0000-0001-9886-5114; Lavery, Lawrence/0000-0002-7920-9952 NR 43 TC 36 Z9 37 U1 0 U2 25 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD FEB PY 2012 VL 28 SU 1 BP 142 EP 162 DI 10.1002/dmrr.2247 PG 21 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 880AY UT WOS:000299377700025 PM 22271738 ER PT J AU Lipsky, BA Peters, EJG Senneville, E Berendt, AR Embil, JM Lavery, LA Urbancic-Rovan, V Jeffcoate, WJ AF Lipsky, B. A. Peters, E. J. G. Senneville, E. Berendt, A. R. Embil, J. M. Lavery, L. A. Urbancic-Rovan, V. Jeffcoate, W. J. TI Expert opinion on the management of infections in the diabetic foot SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article; Proceedings Paper CT 6th International Symposium on the Diabetic Foot CY MAY 10-14, 2011 CL Noordwijkerhout, NETHERLANDS DE diabetes mellitus; diabetic foot; infection; osteomyelitis; antibiotics; surgery; systematic review ID RESISTANT STAPHYLOCOCCUS-AUREUS; TO-BONE TEST; SOFT-TISSUE INFECTIONS; CLASSIFICATION-SYSTEM; SURGICAL-TREATMENT; NUCLEAR-MEDICINE; LOWER-EXTREMITY; RISK-FACTORS; UNSUSPECTED OSTEOMYELITIS; CONSERVATIVE MANAGEMENT AB This update of the International Working Group on the Diabetic Foot incorporates some information from a related review of diabetic foot osteomyelitis (DFO) and a systematic review of the management of infection of the diabetic foot. The pathophysiology of these infections is now well understood, and there is a validated system for classifying the severity of infections based on their clinical findings. Diagnosing osteomyelitis remains difficult, but several recent publications have clarified the role of clinical, laboratory and imaging tests. Magnetic resonance imaging has emerged as the most accurate means of diagnosing bone infection, but bone biopsy for culture and histopathology remains the criterion standard. Determining the organisms responsible for a diabetic foot infection via culture of appropriately collected tissue specimens enables clinicians to make optimal antibiotic choices based on culture and sensitivity results. In addition to culture-directed antibiotic therapy, most infections require some surgical intervention, ranging from minor debridement to major resection, amputation or revascularization. Clinicians must also provide proper wound care to ensure healing of the wound. Various adjunctive therapies may benefit some patients, but the data supporting them are weak. If properly treated, most diabetic foot infections can be cured. Providers practising in developing countries, and their patients, face especially challenging situations. Copyright (C) 2012 John Wiley & Sons, Ltd. C1 [Lipsky, B. A.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Peters, E. J. G.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Senneville, E.] Gustave Dron Hosp, Tourcoing, France. [Berendt, A. R.] Oxford Univ Hosp NHS Trust, Bone Infect Unit, Nuffield Orthopaed Ctr, Oxford, England. [Embil, J. M.] Univ Manitoba, Winnipeg, MB, Canada. [Lavery, L. A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Lavery, L. A.] Parkland Hosp, Dallas, TX USA. [Urbancic-Rovan, V.] Univ Med Ctr, Ljubljana, Slovenia. [Jeffcoate, W. J.] Nottingham Univ Hosp Trust, Nottingham, England. RP Lipsky, BA (reprint author), Univ Washington, Director Primary Care Clin, VA Puget Sound, VA Puget Sound Syst, 1660 S Columbian Way S-123-GMS, Seattle, WA 98108 USA. EM dblipsky@hotmail.com RI Peters, Edgar /B-7790-2014; OI Lipsky, Benjamin A./0000-0001-9886-5114; Lavery, Lawrence/0000-0002-7920-9952 NR 160 TC 78 Z9 79 U1 0 U2 22 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD FEB PY 2012 VL 28 SU 1 BP 163 EP 178 DI 10.1002/dmrr.2248 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 880AY UT WOS:000299377700026 PM 22271739 ER PT J AU Lipsky, BA Peters, EJG Berendt, AR Senneville, E Bakker, K Embil, JM Lavery, LA Urbancic-Rovan, V Jeffcoate, WJ AF Lipsky, B. A. Peters, E. J. G. Berendt, A. R. Senneville, E. Bakker, K. Embil, J. M. Lavery, L. A. Urbancic-Rovan, V. Jeffcoate, W. J. TI Specific guidelines for the treatment of diabetic foot infections 2011 SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Editorial Material DE diabetes mellitus; diabetic foot; infection; osteomyelitis; antibiotics; surgery; systematic review C1 [Lipsky, B. A.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Peters, E. J. G.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Berendt, A. R.] Nuffield Orthopaed Ctr, Oxford OX3 7LD, England. [Senneville, E.] Gustave Dron Hosp, Tourcoing, France. [Bakker, K.; Embil, J. M.] IWGDF, Heemstede, Netherlands. [Lavery, L. A.] Univ Manitoba, Winnipeg, MB, Canada. [Urbancic-Rovan, V.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Urbancic-Rovan, V.] Parkland Hosp, Dallas, TX USA. [Jeffcoate, W. J.] Univ Med Ctr, Ljubljana, Slovenia. [Jeffcoate, W. J.] Nottingham Univ Hosp NHS Trust, Nottingham, England. RP Lipsky, BA (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way S-123 GMS, Seattle, WA 98108 USA. EM dblipsky@hotmail.com RI Peters, Edgar /B-7790-2014; OI Lipsky, Benjamin A./0000-0001-9886-5114; Lavery, Lawrence/0000-0002-7920-9952 NR 0 TC 28 Z9 30 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD FEB PY 2012 VL 28 SU 1 BP 234 EP 235 DI 10.1002/dmrr.2251 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 880AY UT WOS:000299377700031 PM 22271744 ER PT J AU Hershcovici, T Poh, CH Fass, OZ Ashpole, N Akiba, Y Guillen-Rodriguez, JM Kaunitz, JD Fass, R AF Hershcovici, Tiberiu Poh, Choo H. Fass, Ofer Z. Ashpole, Nicole Akiba, Yasutada Guillen-Rodriguez, Jose M. Kaunitz, Jonathan D. Fass, Ronnie TI Oesophageal sensation in response to high PCO2 and acidic solutions in nonerosive reflux disease SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE Acid perfusion; heartburn; high PCO2 solution; nonerosive reflux disease ID PROTON PUMP INHIBITOR; HEALTH SURVEY QUESTIONNAIRE; TRPV1 GENE-EXPRESSION; CARBONIC-ANHYDRASE; BICARBONATE SECRETION; GASTRIC-JUICE; RAT ESOPHAGUS; EPITHELIUM; IMPEDANCE; SYMPTOMS AB Background Heartburn is commonly associated with the presence of acid in the oesophageal lumen. However, in patients with nonerosive reflux disease (NERD), the mechanism by which acid traverses the mucosa is not clear. We hypothesized that the luminal acid signal traverses the oesophageal epithelium in the form of the highly permeant gas CO2, which then is reconverted to H+ in the submucosa. Materials and methods Ten patients with heartburn, normal upper endoscopy and increased oesophageal acid exposure (NERD patients) and 10 healthy subjects were enrolled. Perceptual responses to intraoesophageal acid (0.1 N HCl solution) and a high PCO2 solution were determined using a randomized cross over design. Stimulusresponse functions to perfusions were quantified by three parameters: lag time to symptom perception, intensity rating and perfusion sensitivity score. Results In NERD patients, the difference in lag time to typical symptom perception, intensity rating and perfusion sensitivity score between high PCO2 and acid perfusions was statistically significant (P = 0.02, 0.01 and 0.02, respectively). However, the difference in the same perfusion parameters between acid and high PCO2 perfusions was nonsignificant in healthy controls. When NERD and controls were compared, the difference between the different perfusion variables was nonsignificant (adjusted to age). Conclusions In NERD subjects, acid perfusion reliably evoked heartburn symptoms of greater intensity than in healthy controls. Nevertheless, a high PCO2 perfusion failed to produce symptoms in either group. C1 [Hershcovici, Tiberiu; Poh, Choo H.; Fass, Ofer Z.; Ashpole, Nicole; Fass, Ronnie] Univ Arizona, Hlth Sci Ctr, Tucson, AZ 85723 USA. [Hershcovici, Tiberiu; Poh, Choo H.; Fass, Ofer Z.; Ashpole, Nicole; Fass, Ronnie] So Arizona VA Hlth Care Syst, Neuroenter Clin Res Grp, Gastroenterol Sect, Tucson, AZ 85723 USA. [Akiba, Yasutada; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Med, Greater Los Angles Vet Affairs Healthcare Syst, Los Angeles, CA 90024 USA. [Akiba, Yasutada; Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA USA. [Guillen-Rodriguez, Jose M.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85721 USA. RP Fass, R (reprint author), Univ Arizona, Hlth Sci Ctr, 601 S 6th Ave,1-111-GI, Tucson, AZ 85723 USA. EM ronnie.fass@va.gov FU NIDDK NIH HHS [R01 DK054221] NR 44 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD FEB PY 2012 VL 42 IS 2 BP 195 EP 202 DI 10.1111/j.1365-2362.2011.02560.x PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 873JC UT WOS:000298877500011 PM 21679182 ER PT J AU Peters, U Hutter, CM Hsu, L Schumacher, FR Conti, DV Carlson, CS Edlund, CK Haile, RW Gallinger, S Zanke, BW Lemire, M Rangrej, J Vijayaraghavan, R Chan, AT Hazra, A Hunter, DJ Ma, J Fuchs, CS Giovannucci, EL Kraft, P Liu, Y Chen, L Jiao, S Makar, KW Taverna, D Gruber, SB Rennert, G Moreno, V Ulrich, CM Woods, MO Green, RC Parfrey, PS Prentice, RL Kooperberg, C Jackson, RD LaCroix, AZ Caan, BJ Hayes, RB Berndt, SI Chanock, SJ Schoen, RE Chang-Claude, J Hoffmeister, M Brenner, H Frank, B Bezieau, S Kury, S Slattery, ML Hopper, JL Jenkins, MA Le Marchand, L Lindor, NM Newcomb, PA Seminara, D Hudson, TJ Duggan, DJ Potter, JD Casey, G AF Peters, Ulrike Hutter, Carolyn M. Hsu, Li Schumacher, Fredrick R. Conti, David V. Carlson, Christopher S. Edlund, Christopher K. Haile, Robert W. Gallinger, Steven Zanke, Brent W. Lemire, Mathieu Rangrej, Jagadish Vijayaraghavan, Raakhee Chan, Andrew T. Hazra, Aditi Hunter, David J. Ma, Jing Fuchs, Charles S. Giovannucci, Edward L. Kraft, Peter Liu, Yan Chen, Lin Jiao, Shuo Makar, Karen W. Taverna, Darin Gruber, Stephen B. Rennert, Gad Moreno, Victor Ulrich, Cornelia M. Woods, Michael O. Green, Roger C. Parfrey, Patrick S. Prentice, Ross L. Kooperberg, Charles Jackson, Rebecca D. LaCroix, Andrea Z. Caan, Bette J. Hayes, Richard B. Berndt, Sonja I. Chanock, Stephen J. Schoen, Robert E. Chang-Claude, Jenny Hoffmeister, Michael Brenner, Hermann Frank, Bernd Bezieau, Stephane Kuery, Sebastien Slattery, Martha L. Hopper, John L. Jenkins, Mark A. Le Marchand, Loic Lindor, Noralane M. Newcomb, Polly A. Seminara, Daniela Hudson, Thomas J. Duggan, David J. Potter, John D. Casey, Graham TI Meta-analysis of new genome-wide association studies of colorectal cancer risk SO HUMAN GENETICS LA English DT Article ID MULTILOCUS GENOTYPE DATA; SUSCEPTIBILITY LOCI; COMMON VARIANTS; RARE VARIANTS; 8Q24; SCAN; INFERENCE; DISEASES; 5P15.33; GENE AB Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8 x 10(-8)). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p < 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p value 0.03; combined p value 7.3 x 10(-5)). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p value 0.03; combined p value 1.9 x 10(-4)). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer. C1 [Peters, Ulrike; Hutter, Carolyn M.; Carlson, Christopher S.; Jiao, Shuo; Makar, Karen W.; Ulrich, Cornelia M.; LaCroix, Andrea Z.; Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Peters, Ulrike; Ulrich, Cornelia M.; Potter, John D.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Hsu, Li] Fred Hutchinson Canc Res Ctr, Biostat & Biomath Program, Seattle, WA 98104 USA. [Schumacher, Fredrick R.; Conti, David V.; Haile, Robert W.; Casey, Graham] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Gallinger, Steven] Toronto Gen Hosp, Univ Hlth Network, Dept Surg, Toronto, ON, Canada. [Zanke, Brent W.] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Lemire, Mathieu; Rangrej, Jagadish; Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Vijayaraghavan, Raakhee; Taverna, Darin; Duggan, David J.] Translat Genom Res Inst, Phoenix, AZ USA. [Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. [Chan, Andrew T.; Hazra, Aditi; Ma, Jing; Fuchs, Charles S.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.; Hazra, Aditi; Ma, Jing; Fuchs, Charles S.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Hazra, Aditi; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Liu, Yan] Stephens & Associates, Dallas Res Ctr, Dallas, TX USA. [Chen, Lin] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Gruber, Stephen B.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Rennert, Gad] Technion Fac Med, Haifa, Israel. [Moreno, Victor] Catalan Inst Oncol IDIBELL, Biostat & Bioinformat Unit, Barcelona, Spain. [Ulrich, Cornelia M.] German Canc Res Ctr, Div Prevent Oncol, D-6900 Heidelberg, Germany. [Woods, Michael O.; Green, Roger C.] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF, Canada. [Parfrey, Patrick S.] Mem Univ Newfoundland, Fac Med, Discipline Med, St John, NF, Canada. [Prentice, Ross L.; Kooperberg, Charles; Potter, John D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Caan, Bette J.] Kaiser Permanente Med Care Program, Div Res, Oakland, CA USA. [Hayes, Richard B.] NYU, Dept Environm Med, Sch Med, Div Epidemiol, New York, NY 10016 USA. [Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA. [Schoen, Robert E.] Univ Pittsburgh, Dept Epidemiol, Med Ctr, Pittsburgh, PA 15261 USA. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Hoffmeister, Michael; Brenner, Hermann; Frank, Bernd] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany. [Bezieau, Stephane; Kuery, Sebastien] Ctr Hosp Univ CHU Nantes, Serv Genet Med, Nantes, France. [Slattery, Martha L.] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA. [Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Le Marchand, Loic] Univ Hawaii Manoa, Program Epidemiol, Canc Res Ctr Hawaii, Honolulu, HI 96822 USA. [Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. RP Peters, U (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA. EM upeters@fhcrc.org; gcasey@usc.edu RI Hoffmeister, Michael/B-5745-2012; Gallinger, Steven/E-4575-2013; KURY, Sebastien/G-5971-2015; Bezieau, stephane/G-5621-2015; Jenkins, Mark/P-7803-2015; Brenner, Hermann/B-4627-2017; OI Hoffmeister, Michael/0000-0002-8307-3197; Moreno, Victor/0000-0002-2818-5487; KURY, Sebastien/0000-0001-5497-0465; Bezieau, stephane/0000-0003-0095-1319; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Hayes, Richard/0000-0002-0918-661X; Potter, John/0000-0001-5439-1500 FU Canadian Cancer Society Research Institute; Ontario Institute for Cancer Research; National Cancer Institute, National Institutes of Health [CA-95-011, U01 CA122839]; Australasian Colorectal Cancer Family Registry [U01 CA097735]; Familial Colorectal Neoplasia Collaborative Group [U01 CA074799]; Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01 CA074800]; Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; Seattle Colorectal Cancer Family Registry [U01 CA074794]; University of Hawaii Colorectal Cancer Family Registry [U01 CA074806]; German Research Council (Deutsche Forschungsgemeinschaft [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [R01 CA48998]; National Cancer Institute, Institutes of Health, U.S. Department of Health and Human Services [R01 CA059045, R25 CA094880, U01 CA137088]; regional Hospital Clinical Research Program (PHRC); Regional Council of Pays de la Loire; Groupement des Entreprises Francaises dans la LUtte contre le Cancer (GEFLUC); Association Anne de Bretagne Genetique and the Ligue Regionale Contre le Cancer (LRCC); National Institutes of Health [P01 CA 055075, R01 137178, P50 CA 127003, P01 CA 087969]; National Institutes of Health, U.S. Department of Health and Human Services [R01 CA81488, U01 CA74783]; Interdisciplinary Health Research Team from the Canadian Institutes of Health Research [CRT 43821]; National Cancer Institute of Canada [18223, 18226]; Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services; National Cancer Institute; National Institutes of Health, Genes, Environment and Health Initiative [NIH GEI] [Z01 CP 010200, U01 HG 004438]; 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, 268200764316C] FX ARCTIC: This work was supported by the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. TJH and BWZ are recipients of Senior Investigator Awards from the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research.; CCFR: This work was supported by the National Cancer Institute, National Institutes of Health under RFA # CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. This genome-wide scan was supported by the National Cancer Institute, National Institutes of Health by U01 CA122839. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CFRs, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CFR. The following Colon CFR centers contributed data to this manuscript and were supported by the following sources: Australasian Colorectal Cancer Family Registry (U01 CA097735), Familial Colorectal Neoplasia Collaborative Group (U01 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), Seattle Colorectal Cancer Family Registry (U01 CA074794), University of Hawaii Colorectal Cancer Family Registry (U01 CA074806).; DACHS: This work was supported by grants from the German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). We thank all participants and cooperating clinicians, and Ute Handte-Daub, Belinda-Su Kaspereit and Ursula Eilber for excellent technical assistance.; DALS: This work was supported by the National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (R01 CA48998 to MLS).; DALS, PLCO and WHI GWAS: Funding for the genome-wide scan of DALS, PLCO, and DALS was provided by the National Cancer Institute, Institutes of Health, U.S. Department of Health and Human Services (R01 CA059045 to UP). CMH was supported by a training grant from the National Cancer Institute, Institutes of Health, U.S. Department of Health and Human Services (R25 CA094880).; FRENCH: This work was funded by a regional Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la LUtte contre le Cancer (GEFLUC), the Association Anne de Bretagne Genetique and the Ligue Regionale Contre le Cancer (LRCC).; GECCO: Funding for GECCO infrastructure is supported by National Cancer Institute, Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088 to UP).; HPFS: This work was supported by the National Institutes of Health (P01 CA 055075 to C. S. F., R01 137178 to A. T. C., and P50 CA 127003 to C. S. F.). We acknowledge Patrice Soule and Hardeep Ranu for genotyping at the Dana-Farber Harvard Cancer Center High Throughput Polymorphism Core under the supervision of David J. Hunter, and Carolyn Guo for programming assistance.; MECC: This work was supported by the National Institutes of Health, U.S. Department of Health and Human Services (R01 CA81488 to SBG and GR).; NFCCR: This work was supported by an Interdisciplinary Health Research Team award from the Canadian Institutes of Health Research (CRT 43821); the National Institutes of Health, U.S. Department of Health and Human Services (U01 CA74783); and National Cancer Institute of Canada grants (18223 and 18226). The authors wish to acknowledge the contribution of Alexandre Belisle and the genotyping team of the McGill University and Genome Quebec Innovation Centre, Montreal, Canada, for genotyping the Sequenom panel in the NFCCR samples.; NHS: This work was supported by the National Institutes of Health (P01 CA 087969 to ELG, R01 137178 to ATC, and P50 CA 127003 to CSF). We acknowledge Patrice Soule and Hardeep Ranu for genotyping at the Dana-Farber Harvard Cancer Center High Throughput Polymorphism Core under the supervision of David J. Hunter, and Carolyn Guo for programming assistance.; PLCO: This research was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services. The authors thank Drs. Christine Berg and Philip Prorok at the Division of Cancer Prevention at the National Cancer Institute, and investigators and staff from the screening centers of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, Mr. Thomas Riley and staff at Information Management Services, Inc., Ms. Barbara O'Brien and staff at Westat, Inc., and Mr. Tim Sheehy and staff at SAIC-Frederick. Most importantly, we acknowledge the study participants for their contributions to making this study possible.; Control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) prostate cancer scan were supported by the Intramural Research Program of the National Cancer Institute. The datasets used in this analysis were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data_access.html) through dbGaP accession number 000207v.1p1.c1 (National Cancer Institute 2009; Yeager et al. 2007). Control samples were also genotyped as part of the GWAS of Lung Cancer and Smoking. Funding for this work was provided through the National Institutes of Health, Genes, Environment and Health Initiative [NIH GEI] (Z01 CP 010200). The human subjects participating in the GWAS are derived from the Prostate, Lung, Colon and Ovarian Screening Trial and the study is supported by intramural resources of the National Cancer Institute. Assistance with genotype cleaning, as well as with general study coordination, was provided by the Gene Environment Association Studies, GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NHI GEI (U01 HG 004438). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number ph000093.v2.p2.c1.; 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, 44221, and 268200764316C. NR 70 TC 102 Z9 103 U1 0 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD FEB PY 2012 VL 131 IS 2 BP 217 EP 234 DI 10.1007/s00439-011-1055-0 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 876QQ UT WOS:000299123000006 PM 21761138 ER PT J AU Lachke, SA Higgins, AW Inagaki, M Saadi, I Xi, QC Long, M Quade, BJ Talkowski, ME Gusella, JF Fujimoto, A Robinson, ML Yang, Y Duong, QT Shapira, I Motro, B Miyoshi, J Takai, Y Morton, CC Maas, RL AF Lachke, Salil A. Higgins, Anne W. Inagaki, Maiko Saadi, Irfan Xi, Qiongchao Long, Michelle Quade, Bradley J. Talkowski, Michael E. Gusella, James F. Fujimoto, Atsuko Robinson, Michael L. Yang, Ying Duong, Quynh T. Shapira, Irit Motro, Benny Miyoshi, Jun Takai, Yoshimi Morton, Cynthia C. Maas, Richard L. TI The cell adhesion gene PVRL3 is associated with congenital ocular defects SO HUMAN GENETICS LA English DT Article ID TRANSCRIPTION FACTOR; MISSENSE MUTATION; MOLECULE NECTIN; EYE DEVELOPMENT; JUVENILE-ONSET; MURINE KINASES; N-CADHERIN; MOUSE EYE; CATARACT; LENS AB We describe a male patient (patient DGAP113) with a balanced translocation, 46,XY,t(1;3)(q31.3;q13.13), severe bilateral congenital cataracts, CNS abnormalities and mild developmental delay. Fluorescence in situ hybridization (FISH) and suppression PCR demonstrated that the chromosome 3 breakpoint lies similar to 515 kb upstream of the PVRL3 gene, while the chromosome 1 breakpoint lies similar to 50 kb upstream of the NEK7 gene. Despite the fact that NEK7 is closer to a translocation breakpoint than PVRL3, NEK7 transcript levels are unaltered in patient DGAP113 lymphoblastoid cells and Nek7-deficient mice exhibit no detectable ocular phenotype. In contrast, the expression of PVRL3, which encodes the cell adhesion protein Nectin 3, is significantly reduced in patient DGAP113 lymphoblastoid cells, likely due to a position effect caused by the chromosomal translocation. Nectin 3 is expressed in the mouse embryonic ciliary body and lens. Moreover, Pvrl3 knockout mice as well as a spontaneous mouse mutant ari (anterior retinal inversion), that maps to the Pvrl3 locus, exhibit lens and other ocular defects involving the ciliary body. Collectively, these data identify PVRL3 as a critical gene involved in a Nectin-mediated cell-cell adhesion mechanism in human ocular development. C1 [Lachke, Salil A.; Saadi, Irfan; Xi, Qiongchao; Maas, Richard L.] Harvard Univ, Sch Med, Dept Med, Div Genet,Brigham & Womens Hosp, Boston, MA 02115 USA. [Lachke, Salil A.] Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. [Higgins, Anne W.; Long, Michelle; Quade, Bradley J.; Morton, Cynthia C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Higgins, Anne W.; Long, Michelle; Quade, Bradley J.; Morton, Cynthia C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Inagaki, Maiko] Hiroshima Univ, Inst Radiat Biol & Med, Radiat Res Ctr Frontier Sci Res, Minami Ku, Hiroshima 7348553, Japan. [Talkowski, Michael E.; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. [Talkowski, Michael E.; Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Fujimoto, Atsuko] Univ So Calif, Med Ctr, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. [Robinson, Michael L.] Miami Univ, Dept Zool, Oxford, OH 45056 USA. [Yang, Ying] Columbus Childrens Res Inst, Ctr Human & Mol Genet, Columbus, OH 43205 USA. [Duong, Quynh T.] Ohio State Univ, Coll Optometry, Columbus, OH 43210 USA. [Shapira, Irit; Motro, Benny] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel. [Miyoshi, Jun] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Mol Biol, Osaka 5378511, Japan. [Takai, Yoshimi] Kobe Univ, Grad Sch Med, Div Mol & Cellular Biol, Kobe, Hyogo 6500017, Japan. RP Maas, RL (reprint author), Harvard Univ, Sch Med, Dept Med, Div Genet,Brigham & Womens Hosp, Boston, MA 02115 USA. EM maas@genetics.med.harvard.edu OI Saadi, Irfan/0000-0002-6250-6651 FU NIH [5R01EY10123-15, 5R01HD060050-02, 5P01GM061354-07, R01EY021505, R01EY12995, T35-EY07151] FX We thank the subject and his relatives for participating in the Developmental Genome Anatomy Project and Heather Ferguson, Chantal Kelly and Shahrin Ahsan for assistance as study coordinators. This work was supported by NIH grants 5R01EY10123-15 (RLM), 5R01HD060050-02 (RLM), 5P01GM061354-07 (CCM, RLM, JFG, BJQ), R01EY021505 (SAL), R01EY12995 (MLR), and T35-EY07151 (QTD). All experiments comply with the current laws of the countries (US, Israel and Japan) in which they were performed. NR 70 TC 15 Z9 15 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD FEB PY 2012 VL 131 IS 2 BP 235 EP 250 DI 10.1007/s00439-011-1064-z PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 876QQ UT WOS:000299123000007 PM 21769484 ER PT J AU Konrad-Martin, D Reavis, KM McMillan, GP Dille, MF AF Konrad-Martin, Dawn Reavis, Kelly M. McMillan, Garnett P. Dille, Marilyn F. TI Multivariate DPOAE metrics for identifying changes in hearing: Perspectives from ototoxicity monitoring SO INTERNATIONAL JOURNAL OF AUDIOLOGY LA English DT Article DE Otoacoustic emission; noise-induced hearing loss; ototoxicity monitoring ID PRODUCT OTOACOUSTIC EMISSIONS; FAST FOURIER-TRANSFORMS; SENSORY CELL LOSS; OUTER HAIR-CELLS; DISTORTION-PRODUCT; NOISE EXPOSURE; SUPPRESSION EXPERIMENTS; IMPAIRED SUBJECTS; BASILAR-MEMBRANE; TEST-PERFORMANCE AB Distortion-product otoacoustic emissions (DPOAEs) provide a window into real-time cochlear mechanical function. Yet, relationships between the changes in DPOAE metrics and auditory sensitivity are still poorly understood. Explicating these relationships might support the use of DPOAEs in hearing conservation programs (HCPs) for detecting early damage leading to noise-induced hearing loss (NIHL) so that mitigating steps might be taken to limit any lasting damage. This report describes the development of DPOAE-based statistical models to assess the risk of hearing loss from cisplatin treatment among cancer patients. Ototoxicity risk assessment (ORA) models were constructed using a machine learning paradigm in which partial least squares and leave-one-out cross-validation were applied, yielding optimal screening algorithms from a set of known risk factors for ototoxicity and DPOAE changes from pre-exposure baseline measures. Single DPOAE metrics alone were poorer indicators of the risk of ototoxic hearing shifts than the best performing multivariate models. This finding suggests that multivariate approaches applied to the use of DPOAEs in a HCP, will improve the ability of DPOAE measures to identify ears with noise-induced mechanical damage and/or hearing loss at each monitoring interval. This prediction must be empirically assessed in noise-exposed subjects. C1 [Konrad-Martin, Dawn; Reavis, Kelly M.; McMillan, Garnett P.; Dille, Marilyn F.] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Auditory Res NCRAR, Portland, OR 97239 USA. [Konrad-Martin, Dawn; Dille, Marilyn F.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [McMillan, Garnett P.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Konrad-Martin, D (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res NCRAR, 3710 US Vet Hosp Rd,P5 NCRAR, Portland, OR 97239 USA. EM dawn.martin@va.gov OI Reavis, Kelly/0000-0002-4906-1010 FU National Center for Rehabilitative Auditory Research; Office of Rehabilitation Research and Development Service, Department of Veterans Affairs [C2113R, C7223R, C7113N] FX We thank Colleen Le Prell, Lynne Marshall, and an anonymous reviewer for their comments on an earlier version of this manuscript. Work was supported by the National Center for Rehabilitative Auditory Research, and the Office of Rehabilitation Research and Development Service, Department of Veterans Affairs (Grants awarded to the first and last authors, C2113R, C7223R, and C7113N). This work was presented at the National Hearing Conservation Association 2011 Annual Conference in Mesa, USA. NR 68 TC 5 Z9 5 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1499-2027 J9 INT J AUDIOL JI Int. J. Audiol. PD FEB PY 2012 VL 51 SU 1 BP S51 EP S62 DI 10.3109/14992027.2011.635713 PG 12 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 880DL UT WOS:000299384800007 PM 22264063 ER PT J AU Childs, SK Kozak, KR Friedmann, AM Yeap, BY Adams, J MacDonald, SM Liebsch, NJ Tarbell, NJ Yock, TI AF Childs, Stephanie K. Kozak, Kevin R. Friedmann, Alison M. Yeap, Beow Y. Adams, Judith MacDonald, Shannon M. Liebsch, Norbert J. Tarbell, Nancy J. Yock, Torunn I. TI PROTON RADIOTHERAPY FOR PARAMENINGEAL RHABDOMYOSARCOMA: CLINICAL OUTCOMES AND LATE EFFECTS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Parameningeal rhabdomyosarcoma; Pediatric; Proton radiotherapy; Late effects; Conformal radiotherapy ID INTENSITY-MODULATED RADIOTHERAPY; INTERGROUP RHABDOMYOSARCOMA; NECK RHABDOMYOSARCOMA; NONMETASTATIC RHABDOMYOSARCOMA; INTERNATIONAL-SOCIETY; PEDIATRIC-ONCOLOGY; CHILDHOOD-CANCER; SOFT-TISSUE; CHILDREN; HEAD AB Purpose: To report the clinical outcome and late side effect profile of proton radiotherapy in the treatment of children with parameningeal rhabdomyosarcoma (PM-RMS). Methods and Materials: Seventeen consecutive children with PM-RMS were treated with proton radiotherapy at Massachusetts General Hospital between 1996 and 2005. We reviewed the medical records of all patients and asked referring physicians to report specific side effects of interest. Results: Median patient age at diagnosis was 3.4 years (range, 0.4-17.6). Embryonal (n = 11), alveolar (n = 4), and undifferentiated (n = 2) histologies were represented. Ten patients (59%) had intracranial extension. Median prescribed dose was 50.4 cobalt gray equivalents (GyRBE) (range, 50.4-56.0 GyRBE) delivered in 1.8-2.0-GyRBE daily fractions. Median follow-up was 5.0 years for survivors. The 5-year failure-free survival estimate was 59% (95% confidence interval, 33-79%), and overall survival estimate was 64% (95% confidence interval, 37 82%). Among the 7 patients who failed, sites of first recurrence were local only = 2), regional only (n = 2), distant only (n = 2), and local and distant (n = 1). Late effects related to proton radiotherapy in the 10 recurrence-free patients (median follow-up, 5 years) include failure to maintain height velocity (n = 3), endocrinopathies = 2), mild facial hypoplasia (n = 7), failure of permanent tooth eruption (n = 3), dental caries (n = 5), and chronic nasal/sinus congestion (n = 2). Conclusions: Proton radiotherapy for patients with PM-RMS yields tumor control and survival comparable to that in historical controls with similar poor prognostic factors. Furthermore, rates of late effects from proton radiotherapy compare favorably to published reports of photon-treated cohorts. (C) 2012 Elsevier Inc. C1 [Yock, Torunn I.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol,Med Sch, Boston, MA 02114 USA. [Friedmann, Alison M.] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Oncol, Sch Med, Boston, MA 02114 USA. [Yeap, Beow Y.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, Boston, MA 02114 USA. [Kozak, Kevin R.] Univ Wisconsin, Canc Ctr Johnson Creek, Dept Radiat Oncol, Madison, WI USA. RP Yock, TI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol,Med Sch, 55 Fruit St, Boston, MA 02114 USA. EM tyock@partners.org FU NCRR NIH HHS [UL1 RR025011-04, UL1 RR025011-05, UL1 RR025011] NR 23 TC 36 Z9 38 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2012 VL 82 IS 2 BP 635 EP 642 DI 10.1016/j.ijrobp.2010.11.048 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 878FC UT WOS:000299239900030 PM 21377294 ER PT J AU Morse, LR Sudhakar, S Danilack, V Tun, C Lazzari, A Gagnon, DR Garshick, E Battaglino, RA AF Morse, Leslie R. Sudhakar, Supreetha Danilack, Valery Tun, Carlos Lazzari, Antonio Gagnon, David R. Garshick, Eric Battaglino, Ricardo A. TI Association between sclerostin and bone density in chronic spinal cord injury SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BONE FRACTURE; OSTEOPOROSIS; SCLEROSTIN; SPINAL CORD INJURY; REHABILITATION MEDICINE ID REDUCES OSTEOCYTE EXPRESSION; X-RAY ABSORPTIOMETRY; MECHANICAL STIMULATION; POTENTIAL TREATMENT; MINERAL DENSITY; OSTEOPOROSIS; RESORPTION; DELETION; MICE AB Spinal cord injury (SCI) results in profound bone loss due to muscle paralysis and the inability to ambulate. Sclerostin, a Wnt signaling pathway antagonist produced by osteocytes, is a potent inhibitor of bone formation. Short-term studies in rodent models have shown increased sclerostin in response to mechanical unloading that is reversed with reloading. These studies suggest that complete spinal cord injury, a condition resulting in mechanical unloading of the paralyzed lower extremities, will be associated with high sclerostin levels. We assessed the relationship between circulating sclerostin and bone density in 39 subjects with chronic SCI and 10 without SCI. We found that greater total limb bone mineral content was significantly associated with greater circulating levels of sclerostin. Sclerostin levels were reduced, not elevated, in subjects with SCI who use a wheelchair compared with those with SCI who walk regularly. Similarly, sclerostin levels were lower in subjects with SCI who use a wheelchair compared with persons without SCI who walk regularly. These findings suggest that circulating sclerostin is a biomarker of osteoporosis severity, not a mediator of ongoing bone loss, in long-term, chronic paraplegia. This is in contrast to the acute sclerostin-mediated bone loss shown in animal models of mechanical unloading in which high sclerostin levels suppress bone formation. Because these data indicate important differences in the relationship between mechanical unloading, sclerostin, and bone in chronic SCI compared with short-term rodent models, it is likely that sclerostin is not a good therapeutic target to treat chronic SCI-induced osteoporosis. (C) 2012 American Society for Bone and Mineral Research C1 [Morse, Leslie R.; Battaglino, Ricardo A.] Forsyth Inst, Dept Cytokine Biol, Cambridge, MA 02142 USA. [Morse, Leslie R.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Morse, Leslie R.; Sudhakar, Supreetha] Spaulding Rehabil Hosp, Boston, MA USA. [Morse, Leslie R.] VA Boston Healthcare Syst, Spinal Cord Injury Serv, Boston, MA USA. [Danilack, Valery] Harvard Univ, Sch Med, Programs Res, VA Boston, Boston, MA USA. [Tun, Carlos] VA Boston Healthcare Syst, Rehabil Med Serv, Boston, MA USA. [Lazzari, Antonio] VA Boston Healthcare Syst, Primary Care Sect, Boston, MA USA. [Lazzari, Antonio] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gagnon, David R.] Boston Univ, VA Cooperat Studies Program, VA Boston Healthcare Syst, Sch Publ Hlth,Dept Biostat, Boston, MA USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. [Garshick, Eric] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [Battaglino, Ricardo A.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Battaglino, RA (reprint author), Forsyth Inst, Dept Cytokine Biol, 245 1st St, Cambridge, MA 02142 USA. EM rbattaglino@forsyth.org RI battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015; OI Morse, Leslie/0000-0002-7426-6341; Gagnon, David/0000-0002-6367-3179 FU National Institute of Child Health and Human Development [R21HD057030, R21HD057030-02S1]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [1R01AR059270-01]; Office of Research and Development, Rehabilitation Research and Development [B6618R]; Massachusetts Veterans Epidemiology Research and Information Center, Department of Veterans Affairs FX This study received support from: the National Institute of Child Health and Human Development (R21HD057030 and R21HD057030-02S1), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (1R01AR059270-01), the Office of Research and Development, Rehabilitation Research and Development (Merit Review Grant B6618R), and the Massachusetts Veterans Epidemiology Research and Information Center, Cooperative Studies Program, Department of Veterans Affairs. We thank Sam Davis, clinical research coordinator and technician, Boston VA Healthcare System, for assisting with bone density scans; Renee Mikorski and Heather Colburn, research assistants, Boston VA Healthcare System, for collection of anthropometric data; and C. W. Wolff, research coordinator, Spaulding Rehabilitation Hospital, for editorial assistance. NR 30 TC 25 Z9 25 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2012 VL 27 IS 2 BP 352 EP 359 DI 10.1002/jbmr.546 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 879ZP UT WOS:000299373600014 PM 22006831 ER PT J AU Dording, CM Dalton, ED Pencina, MJ Fava, M Mischoulon, D AF Dording, Christina M. Dalton, Elizabeth D. Pencina, Michael J. Fava, Maurizio Mischoulon, David TI Comparison of Academic and Nonacademic Sites in Multi-Center Clinical Trials SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE academic; nonacademic; depression; clinical trial; subject selection ID PLACEBO-RESPONSE; DEPRESSION; DISORDERS; SCALE AB The selection of appropriate subjects is a critical element of successful clinical trials. Failure to properly identify, select, and retain subjects in clinical trials of antidepressant medications may affect the ability to show separation from placebo. Little is known about which type of site, academic or nonacademic, is superior in selecting and retaining appropriate subjects. In the present investigation, the authors conducted a retrospective analysis comparing the performance of academic and nonacademic sites in selecting and retaining appropriate subjects in a recently completed multi-site clinical study of aripiprazole augmentation. The authors used a set of operationalized criteria called the SAFER to identify appropriate study subjects. No significant differences were found in rates of SAFER interview passing, study completion, and clinical outcomes between academic and nonacademic sites. Our findings suggest that academic and nonacademic sites are equally effective in their ability to identify and retain appropriate study participants. C1 [Dording, Christina M.; Dalton, Elizabeth D.; Fava, Maurizio; Mischoulon, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Pencina, Michael J.] Harvard Clin Res Inst, Boston, MA USA. RP Dording, CM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, 6th Floor,1 Bowdoin Sq, Boston, MA 02114 USA. EM cdording@partners.org FU Bristol-Myers Squibb; Abbott Laboratories; Alkermes, Inc; Aspect Medical Systems; AstraZeneca; Bristol-Myers Squibb Company; Cephalon; Eli Lilly and Company; Forest Pharmaceuticals, Inc; GlaxoSmithKline; Johnson & Johnson Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon, Inc; Pamlab, LLC; Pfizer, Inc; Pharmavite; Roche; Sanofi-Aventis; Solvay Pharmaceuticals, Inc; Synthelabo; Wyeth-Ayerst Laboratories; BioResearch; BrainCells, Inc; Cephalon, Inc; Clinical Trials Solutions, LLC; Clintara, LLC; Covidien; EnVivo Pharmaceuticals, Inc; Ganeden Biotech, Inc; Icon Clinical Research; Johnson & Johnson Pharmaceutical Research Development; NARSAD; NCCAM; NIDA; NIMH; Novartis AG; Organon Pharmaceuticals; Pharmavite LLC; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Nordic Naturals; Ganeden; Independent Medical Education (IME) grants FX Christina Dording, MD, has received research support from Abbott Laboratories; Alkermes, Inc; Aspect Medical Systems; AstraZeneca; Bristol-Myers Squibb Company; Cephalon; Eli Lilly and Company; Forest Pharmaceuticals, Inc; Glaxo-SmithKline; Johnson & Johnson Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon, Inc; Pamlab, LLC; Pfizer, Inc; Pharmavite; Roche; Sanofi-Aventis; Solvay Pharmaceuticals, Inc; Synthelabo; and Wyeth-Ayerst Laboratories. Dr Dording has served as an advisor/consultant for Takeda, and has been a speaker for Wyeth-Ayerst Laboratories.; Dr Fava has received research support from the following: Abbott Laboratories; Alkermes, Inc; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells, Inc; Bristol-Myers Squibb; Cephalon, Inc; Clinical Trials Solutions, LLC; Clintara, LLC; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc; Forest Pharmaceuticals, Inc; Ganeden Biotech, Inc; GlaxoSmithKline; Icon Clinical Research; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Novartis AG; Organon Pharmaceuticals; Pamlab, LLC; Pfizer, Inc; Pharmavite LLC; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc; Synthelabo; and Wyeth-Ayerst Laboratories. Dr Fava has provided advisory/consulting to the following: Abbott Laboratories; Affectis Pharmaceuticals AG; Amarin Pharma, Inc; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc; BioMarin Pharmaceuticals, Inc; Bio-vail Corporation; BrainCells Inc; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon, Inc; Clinical Trials Solutions, LLC; CNS Response, Inc; Compellis Pharmaceuticals; Cypress Pharmaceutical, Inc; DiagnoSearch Life Sciences (P) Ltd; Dov Pharmaceuticals, Inc; Eisai, Inc; Eli Lilly and Company; EPIX Pharmaceuticals, Inc; Euthymics Bioscience, Inc; Fabre-Kramer Pharmaceuticals, Inc; Forest Pharmaceuticals, Inc; GenOmind, LLC; GlaxoSmithKline; Gruenthal GmbH; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc; Johnson & Johnson Pharmaceutical Research & Development, LLC; Knoll Pharmaceuticals Corp; Labopharm Inc; Lorex Pharmaceuticals; Lundbeck, Inc; Med-Avante, Inc; Merck & Co, Inc; Methylation Sciences; Neuronetics, Inc; Novartis AG; Nutrition 21; Organon Pharmaceuticals; PamLab, LLC; Pfizer, Inc; PharmaStar; Pharmavite LLC; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc; Psycho-Genics; Psylin Neurosciences, Inc; Rexahn Pharmaceuticals, Inc; Ridge Diagnostics, Inc; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC; Sepracor, Inc; Schering-Plough Corporation; Solvay Pharmaceuticals, Inc; Somaxon Pharmaceuticals, Inc; Somerset Pharmaceuticals, Inc; Synthelabo; Takeda Pharmaceutical Company Ltd; Tetragenex Pharmaceuticals, Inc; TransForm Pharmaceuticals, Inc; Transcept Pharmaceuticals, Inc; Vanda Pharmaceuticals, Inc; and Wyeth-Ayerst Laboratories. Dr Fava has been involved in speaking/publishing for the following: Adamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir Media Group; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Cephalon, Inc; Eli Lilly and Company; Forest Pharmaceuticals, Inc; GlaxoSmithKline; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; Novartis AG; Organon Pharmaceuticals; Pfizer, Inc; PharmaStar; United BioSource, Corp; and Wyeth-Ayerst Laboratories. Dr Fava has equity holdings in Compellis; holds a patent for the Sequential Parallel Comparison Design (SPCD) and a patent application for a combination of azapirones and bupropion in MDD; and he has copyright loyalties for MGH CPFQ, SFI, ATRQ, DESS, and SAFER.; Dr Mischoulon has received research support form Nordic Naturals and Ganeden. He has provided advisory/consulting for Bristol-Meyers Squibb and ICON and has done writing for PamLab. Dr Mischoulon receives royalties from Back Bay Scientific for PMS Escape (patent application pending) and royalties from Lippincott Williams & Wilkins for the textbook Natural Medications for Psychiatric Disorders: Considering the Alternatives (David Mischoulon and Jerrold F. Rosenbaum, Eds.). He receives honoraria from Reed Medical Education (a company working as a logistics collaborator for the MGH Psychiatry Academy). The education programs conducted by the MGH Psychiatry Academy were supported through Independent Medical Education (IME) grants from pharmaceutical companies cosupporting programs along with participant tuition. Commercial entities currently supporting the MGH Psychiatry Academy are listed on the Academy's website www.mghcme.org. No payment from any individual entity or company has exceeded $10,000 per year. NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2012 VL 32 IS 1 BP 65 EP 68 DI 10.1097/JCP.0b013e31823f3b47 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 877GQ UT WOS:000299165900011 PM 22198440 ER PT J AU Dang, BN Giordano, TP Kim, JH AF Dang, Bich N. Giordano, Thomas P. Kim, Jennifer H. TI Sociocultural and Structural Barriers to Care Among Undocumented Latino Immigrants with HIV Infection SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH LA English DT Article DE HIV; AIDS; Illegal immigrant; Undocumented; Latino; Hispanic; Qualitative research ID UNITED-STATES; MEN; COUNTRIES; STIGMA AB Timely entry into HIV care is critical for early initiation of therapy, immunologic recovery and improved survival. However, undocumented Latinos are more likely to enter HIV care late in the disease course and with concurrent AIDS. We conducted a qualitative study to examine the circumstantial, situational and social factors that uniquely affect entry and retention in care for this population. Between June and August 2006, we conducted semi-structured, in-depth, individual interviews with 22 undocumented Latino immigrants living with HIV infection. The interviews were audiotaped, transcribed and reviewed for accuracy. Data was analyzed using a grounded theory approach. Word content was coded and sorted by themes using AnSWR software. Emergent themes related to health care barriers include (1) the challenges of dealing with HIV stigma and rejection from family and community; and (2) the experienced and perceived structural barriers of accessing care as an undocumented individual. Societal intolerance of HIV and stigma-related experiences result in feelings of secrecy and shame. In addition, the undocumented state complicates the situation even further. These unique barriers include fear of deportation, work restrictions, inadequate translation services and difficulties meeting paperwork requirements. This study offers insight into the unique sociocultural and structural barriers faced by undocumented Latinos with HIV infection. Understanding and addressing these barriers will prove vital in the development and implementation of strategies to promote early entry into HIV care. C1 [Dang, Bich N.; Giordano, Thomas P.] Michael E DeBakey VA Med Ctr 152, VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. [Dang, Bich N.; Giordano, Thomas P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Dang, Bich N.; Giordano, Thomas P.] Harris Cty Hosp Dist, Houston, TX USA. [Kim, Jennifer H.] Houston Ryan White Planning Council, Houston, TX USA. RP Dang, BN (reprint author), Michael E DeBakey VA Med Ctr 152, VA Hlth Serv Res & Dev Ctr Excellence, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM bndang@bcm.edu NR 20 TC 28 Z9 28 U1 0 U2 26 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1912 J9 J IMMIGR MINOR HEALT JI J. Immigr. Minor. Health PD FEB PY 2012 VL 14 IS 1 BP 124 EP 131 DI 10.1007/s10903-011-9542-x PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 876QR UT WOS:000299123200014 PM 22012476 ER PT J AU Lee, AJX Roylance, R Sander, J Gorman, P Endesfelder, D Kschischo, M Jones, NP East, P Nicke, B Spassieva, S Obeid, LM Birkbak, NJ Szallasi, Z McKnight, NC Rowan, AJ Speirs, V Hanby, AM Downward, J Tooze, SA Swanton, C AF Lee, Alvin J. X. Roylance, Rebecca Sander, Jil Gorman, Patricia Endesfelder, David Kschischo, Maik Jones, Neil P. East, Philip Nicke, Barbara Spassieva, Stefka Obeid, Lina M. Birkbak, Nicolai Juul Szallasi, Zoltan McKnight, Nicole C. Rowan, Andrew J. Speirs, Valerie Hanby, Andrew M. Downward, Julian Tooze, Sharon A. Swanton, Charles TI CERT depletion predicts chemotherapy benefit and mediates cytotoxic and polyploid-specific cancer cell death through autophagy induction SO JOURNAL OF PATHOLOGY LA English DT Article DE CERT; autophagy; LAMP2; HER2; polyploidy; drug resistance ID BREAST-CANCER; MITOTIC ARREST; CERAMIDE; SENSITIVITY; PACLITAXEL; GENES; ARRAY; SPHINGOLIPIDS; INTERFERENCE; METASTASIS AB Chromosomal instability (CIN) has been implicated in multidrug resistance and the silencing of the ceramide transporter, CERT, promotes sensitization to diverse cytotoxics. An improved understanding of mechanisms governing multidrug sensitization might provide insight into pathways contributing to the death of CIN cancer cells. Using an integrative functional genomics approach, we find that CERT-specific multidrug sensitization is associated with enhanced autophagosomelysosome flux, resulting from the expression of LAMP2 following CERT silencing in colorectal and HER2+ breast cancer cell lines. Live cell microscopy analysis revealed that CERT depletion induces LAMP2-dependent death of polyploid cells following exit from mitosis in the presence of paclitaxel. We find that CERT is relatively over-expressed in HER2+ breast cancer and CERT protein expression acts as an independent prognostic variable and predictor of outcome in adjuvant chemotherapy-treated patients with primary breast cancer. These data suggest that the induction of LAMP2-dependent autophagic flux through CERT targeting may provide a rational approach to enhance multidrug sensitization and potentiate the death of polyploid cells following paclitaxel exposure to limit the acquisition of CIN and intra-tumour heterogeneity. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Lee, Alvin J. X.; Sander, Jil; Endesfelder, David; East, Philip; Nicke, Barbara; McKnight, Nicole C.; Rowan, Andrew J.; Downward, Julian; Tooze, Sharon A.; Swanton, Charles] Canc Res UK London Res Inst, London WC2A 3LY, England. [Roylance, Rebecca; Gorman, Patricia] Queen Mary Univ London, Barts Canc Inst, London EC1M 6BQ, England. [Sander, Jil; Endesfelder, David; Kschischo, Maik] Univ Appl Sci Koblenz, D-53424 Remagen, Germany. [Jones, Neil P.] UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England. [Spassieva, Stefka; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Obeid, Lina M.] Ralph H Johnson Vet Affairs Hosp, Div Gen Internal Med, Charleston, SC 29401 USA. [Birkbak, Nicolai Juul; Szallasi, Zoltan] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Birkbak, Nicolai Juul] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Szallasi, Zoltan] Harvard Univ, Sch Med, Childrens Hosp, Harvard MIT Div Hlth Sci & Technol,Informat Progr, Boston, MA 02115 USA. [Speirs, Valerie; Hanby, Andrew M.] Univ Leeds, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England. [Swanton, Charles] UCL Canc Inst, London WC1E 6BT, England. [Swanton, Charles] Macmillan Canc Ctr, London WC1E 6BT, England. RP Swanton, C (reprint author), Canc Res UK London Res Inst, 44 Lincolns Inn Fields, London WC2A 3LY, England. EM charles.swanton@cancer.org.uk RI Lee, Alvin/A-1047-2017; OI Lee, Alvin/0000-0002-7427-9142; East, Philip/0000-0001-5801-5713; Szallasi, Zoltan/0000-0001-5395-7509; Downward, Julian/0000-0002-2331-4729; obeid, lina/0000-0002-0734-0847 FU National Institute of Health [NCI SPORE P50 CA 89393, R21LM008823-01A1]; Danish Council for Independent Research/Medical Sciences (FSS); Breast Cancer Research Foundation (BCRF); Medical Research Council; CR-UK FX We thank the following: Sarah McClelland, Jasmin Zohren and Rebecca Burrell for help with manuscript preparation; Hannah Armer and Lucy Collinson from the EM facility at Cancer Research UK (CR-UK) LRI and Niamh Murphy for help with the breast cancer TMA cohort. CS is funded by the Medical Research Council and CR-UK. AL, NM, AR, JD and ST are funded by CR-UK. ZS is funded by the National Institute of Health (Grant Nos NCI SPORE P50 CA 89393 and R21LM008823-01A1), the Danish Council for Independent Research/Medical Sciences (FSS) and the Breast Cancer Research Foundation (BCRF). NR 48 TC 19 Z9 19 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD FEB PY 2012 VL 226 IS 3 BP 482 EP 494 DI 10.1002/path.2998 PG 13 WC Oncology; Pathology SC Oncology; Pathology GA 877DY UT WOS:000299158400011 PM 21953249 ER PT J AU Cai, J Tuong, CM Zhang, YP Shields, CB Guo, G Fu, H Gozal, D AF Cai, Jun Tuong, Chi Minh Zhang, Yiping Shields, Christopher B. Guo, Gang Fu, Hui Gozal, David TI Mouse intermittent hypoxia mimicking apnoea of prematurity: effects on myelinogenesis and axonal maturation SO JOURNAL OF PATHOLOGY LA English DT Article DE infantile apnoea; intermittent hypoxia; white matter; oligodendrocyte; axon; brain ID CENTRAL HYPOVENTILATION SYNDROME; SPATIAL-LEARNING DEFICITS; OBSTRUCTIVE SLEEP-APNEA; CENTRAL-NERVOUS-SYSTEM; BIRTH-WEIGHT INFANTS; CELL-CYCLE EXIT; PRETERM INFANTS; OLIGODENDROCYTE DYSFUNCTION; NEUROFILAMENT TRANSPORT; DYNAMIC MICROTUBULES AB Premature babies are at high risk for both infantile apnoea and long-term neurobehavioural deficits. Recent studies suggest that diffuse structural changes in brain white matter are a positive predictor of poor cognitive outcomes. Since oligodendrocyte maturation, myelination, axon development, and synapse formation mainly occur in the third trimester of gestation and first postnatal year, infantile apnoea could lead to and/or exaggerate white matter impairments in preterm neonates. Therefore, we investigated oligodendroglia and axon development in a neonatal mouse model of intermittent hypoxia between postnatal days 2 and 10. During critical phases of central nervous system development, intermittent hypoxia induced hypomyelination in the corpus callosum, striatum, fornix, and cerebellum, but not in the pons or spinal cord. Intermittent hypoxia-elicited alterations in myelin-forming processes were reflected by decreased expression of myelin proteins, including MBP, PLP, MAG, and CNPase, possibly due to arrested maturation of oligodendrocytes. Ultrastructural abnormalities were apparent in the myelin sheath and axon. Immature oligodendrocytes were more vulnerable to neonatal intermittent hypoxia exposures than developing axons, suggesting that hypomyelination may contribute, at least partially, to axonal deficits. Insufficient neurofilament synthesis with anomalous components of neurofilament subunits, beta-tubulin, and MAP2 isoforms indicated immaturity of axons in intermittent hypoxia-exposed mouse brains. In addition, down-regulation of synapsin I, synaptophysin, and Gap-43 phosphorylation suggested a potential stunt in axonogenesis and synaptogenesis. The region-selective and complex impairment in brain white matter induced by intermittent hypoxia was further associated with electrophysiological changes that may underlie long-term neurobehavioural sequelae. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Cai, Jun; Tuong, Chi Minh] Univ Louisville, Dept Pediat, Kosair Childrens Hosp, Res Inst,Sch Med, Louisville, KY 40202 USA. [Cai, Jun] Univ Louisville, Dept Anat Sci & Neurobiol, Sch Med, Louisville, KY 40202 USA. [Cai, Jun; Guo, Gang] Tianjin Med Univ, Metab Dis Hosp, Key Lab Hormone & Dev, Minist Publ Hlth, Tianjin 300070, Peoples R China. [Zhang, Yiping; Shields, Christopher B.] Norton Healthcare, Norton Neurosci Inst, Louisville, KY 40202 USA. [Fu, Hui] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Fu, Hui] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Gozal, David] Univ Chicago, Pritzker Sch Med, Dept Pediat, Chicago, IL 60637 USA. RP Cai, J (reprint author), Univ Louisville, Dept Pediat, 570 S Preston St,Donald Baxter Bldg,Suite 321B, Louisville, KY 40202 USA. EM j0cai002@louisville.edu; dgozal@peds.bsd.uchicago.edu RI Fu, Hui/C-2881-2011 OI Fu, Hui/0000-0003-0252-6009 FU NIH [2P20RR017702-061A1, HL-086662]; Sleep Research Society Foundation; University of Louisville SOM FX We are grateful to Drs Chuck Stiles and John Alberta for the anti-Olig1 and Olig2 antibodies. We thank the Analytical Microscopy Core Facility for providing access to EM instruments, and in particular Cathie Caple and Arkadiusz Slusarczyk for technical assistance. We also thank Dr Nicholas Mellen for critical reading of the manuscript and Dr Robert M Greene for substantial support via the COBRE program. This work was supported by NIH grants 2P20RR017702-061A1 (RMG; JC is a COBRE supported junior faculty and co-investigator) and NIH HL-086662 (DG), a Sleep Research Society Foundation/J Christian Gillin MD Research Grant (JC), and a University of Louisville SOM Basic Grant (JC). NR 79 TC 25 Z9 25 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD FEB PY 2012 VL 226 IS 3 BP 495 EP 508 DI 10.1002/path.2980 PG 14 WC Oncology; Pathology SC Oncology; Pathology GA 877DY UT WOS:000299158400012 PM 21953180 ER PT J AU Jordan, N Waghmare, A Abi-Ghanem, AS Moon, A Salvatore, CM AF Jordan, Nicole Waghmare, Alpana Abi-Ghanem, Alain S. Moon, Aeri Salvatore, Christine M. TI Systemic Mycobacterium avium Complex Infection During Antitumor Necrosis Factor-alpha Therapy in Pediatric Crohn Disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE; TUBERCULOSIS; INFLIXIMAB; DIAGNOSIS C1 [Salvatore, Christine M.] New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Pediat, Div Infect Dis, New York, NY 10065 USA. [Jordan, Nicole] Weill Cornell Med Coll, Dept Pediat, Div Gastroenterol & Nutr, New York, NY USA. [Abi-Ghanem, Alain S.] Weill Cornell Med Coll, Dept Radiol, Div Nucl Med, New York, NY USA. [Moon, Aeri] MassGen Hosp Children, Div Gastroenterol & Nutr, Boston, MA USA. [Waghmare, Alpana] Weill Cornell Med Coll, Dept Pediat, Div Nucl Med, New York, NY USA. RP Salvatore, CM (reprint author), New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Pediat, Div Infect Dis, 505 E 70th St,3rd Floor,POB 578, New York, NY 10065 USA. EM chs2032@med.cornell.edu OI Waghmare, Alpana/0000-0003-2268-9470 NR 13 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD FEB PY 2012 VL 54 IS 2 BP 294 EP 296 DI 10.1097/MPG.0b013e31822938c3 PG 3 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 882SN UT WOS:000299584300026 PM 21694635 ER PT J AU Teles, FR Teles, RP Uzel, NG Song, XQ Torresyap, G Socransky, SS Haffajee, AD AF Teles, F. R. Teles, R. P. Uzel, N. G. Song, X. Q. Torresyap, G. Socransky, S. S. Haffajee, A. D. TI Early microbial succession in redeveloping dental biofilms in periodontal health and disease SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE bacteria; biofilm; ecology; periodontal; succession; supragingival ID INITIAL SUBGINGIVAL COLONIZATION; DNA-DNA HYBRIDIZATION; MICROBIOLOGICAL PARAMETERS; PLAQUE-FORMATION; ORAL MICROFLORA; COMMUNITIES; ENAMEL; SHIFTS; GINGIVITIS; SMOKERS AB Teles FR, Teles RP, Uzel NG, Song XQ, Torresyap G, Socransky SS, Haffajee AD. Early microbial succession in redeveloping dental biofilms in periodontal health and disease. J Periodont Res 2012; 47: 95104. (C) 2011 John Wiley & Sons A/S C1 [Teles, F. R.; Teles, R. P.; Uzel, N. G.; Song, X. Q.; Torresyap, G.; Socransky, S. S.; Haffajee, A. D.] Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA. [Teles, F. R.; Teles, R. P.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Teles, FR (reprint author), Forsyth Inst, Dept Periodontol, 245 1st St, Cambridge, MA 02142 USA. EM fteles@forsyth.org FU NIH/NIDCR [R01 DE14368, R03 DE021742, U01 DE021127]; Forsyth Institute/Harvard Medical School FX This work was supported, in part, by NIH/NIDCR R01 DE14368 (SS), R03 DE021742 (FT) and U01 DE021127 (RT) and the Eleanor and Miles Shore Fellowship Program for Scholars in Medicine (The Forsyth Institute/Harvard Medical School) (F. T.). NR 58 TC 28 Z9 29 U1 1 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD FEB PY 2012 VL 47 IS 1 BP 95 EP 104 DI 10.1111/j.1600-0765.2011.01409.x PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 872GF UT WOS:000298796400012 PM 21895662 ER PT J AU Pace-Schott, EF Nave, G Morgan, A Spencer, RMC AF Pace-Schott, Edward F. Nave, Genevieve Morgan, Alexandra Spencer, Rebecca M. C. TI Sleep-dependent modulation of affectively guided decision-making SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE decision-making; executive function; Iowa Gambling Task; sleep ID IOWA GAMBLING TASK; EXPLICIT KNOWLEDGE; PREFRONTAL CORTEX; DEPRIVATION; MEMORY; PERFORMANCE; ACTIVATION; ROLES AB A question of great interest in current sleep research is whether and how sleep might facilitate complex cognitive skills such as decision-making. The Iowa Gambling Task (IGT) was used to investigate effects of sleep on affect-guided decision-making. After a brief standardized preview of the IGT that was insufficient to learn its underlying rule, participants underwent a 12-h delay containing either a normal nights sleep (Sleep group; N = 28) or continuous daytime wake (Wake group; N = 26). Following the delay, both groups performed the full IGT. To control for circadian effects, two additional groups performed both the preview and the full task either in the morning (N = 17) or the evening (N = 21). In the IGT, four decks of cards were presented. Draws from two advantageous decks yielded low play-money rewards, occasional low losses and, over multiple draws, a net gain. Draws from disadvantageous decks yielded high rewards, occasional high losses and, over multiple draws, a net loss. Participants were instructed to win and avoid losing as much as possible, and better performance was defined as more advantageous draws. Relative to the wake group, the sleep group showed both superior behavioral outcome (more advantageous draws) and superior rule understanding (blindly judged from statements written at task completion). Neither measure differentiated the two control groups. These results illustrate a role of sleep in optimizing decision-making, a benefit that may be brought about by changes in underlying emotional or cognitive processes. C1 [Pace-Schott, Edward F.; Spencer, Rebecca M. C.] Univ Massachusetts, Dept Psychol & Neurosci, Amherst, MA 01003 USA. [Pace-Schott, Edward F.; Morgan, Alexandra] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pace-Schott, Edward F.; Morgan, Alexandra] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Nave, Genevieve] Smith Coll, Northampton, MA 01063 USA. RP Pace-Schott, EF (reprint author), Univ Massachusetts, Dept Psychol, Tobin Hall,Rm 522,135 Hicks Way, Amherst, MA 01003 USA. EM epacesch@psych.umass.edu OI Spencer, Rebecca/0000-0002-8674-2384 FU NIA [R00AG029710] FX This study was supported by NIA grant R00AG029710 to Rebecca M. C. Spencer. We thank Bengi Baran, Tobias Bennett, Stefano Daniele, Brendan Flanagan, Sara Heaton, Shannon McKeon, Victoria Migdal, Lauren A. A. Morris, Enmanuelle Pardilla-Delgado, Amanda Schultz, Elizabeth Shepherd and Chris Zombik for research assistance. All experiments were carried out at the University of Massachusetts, Amherst, MA, USA. NR 32 TC 16 Z9 16 U1 5 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD FEB PY 2012 VL 21 IS 1 BP 30 EP 39 DI 10.1111/j.1365-2869.2011.00921.x PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 879MB UT WOS:000299332300005 PM 21535281 ER PT J AU Eiseman, NA Westover, MB Mietus, JE Thomas, RJ Bianchi, MT AF Eiseman, Nathaniel A. Westover, M. Brandon Mietus, Joseph E. Thomas, Robert J. Bianchi, Matt T. TI Classification algorithms for predicting sleepiness and sleep apnea severity SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE correlation; distribution; mutual information ID EPWORTH SLEEPINESS; HEART HEALTH; LATENCY TEST; DAYTIME SLEEPINESS; RISK-FACTORS; SCALE; ASSOCIATION; PREVALENCE; STROKE; ADULTS AB Identifying predictors of subjective sleepiness and severity of sleep apnea are important yet challenging goals in sleep medicine. Classification algorithms may provide insights, especially when large data sets are available. We analyzed polysomnography and clinical features available from the Sleep Heart Health Study. The Epworth Sleepiness Scale and the apneahypopnea index were the targets of three classifiers: k-nearest neighbor, naive Bayes and support vector machine algorithms. Classification was based on up to 26 features including demographics, polysomnogram, and electrocardiogram (spectrogram). Naive Bayes was best for predicting abnormal Epworth class (010 versus 1124), although prediction was weak: polysomnogram features had 16.7% sensitivity and 88.8% specificity; spectrogram features had 5.3% sensitivity and 96.5% specificity. The support vector machine performed similarly to naive Bayes for predicting sleep apnea class (05 versus >5): 59.0% sensitivity and 74.5% specificity using clinical features and 43.4% sensitivity and 83.5% specificity using spectrographic features compared with the naive Bayes classifier, which had 57.5% sensitivity and 73.7% specificity (clinical), and 39.0% sensitivity and 82.7% specificity (spectrogram). Mutual information analysis confirmed the minimal dependency of the Epworth score on any feature, while the apneahypopnea index showed modest dependency on body mass index, arousal index, oxygenation and spectrogram features. Apnea classification was modestly accurate, using either clinical or spectrogram features, and showed lower sensitivity and higher specificity than common sleep apnea screening tools. Thus, clinical prediction of sleep apnea may be feasible with easily obtained demographic and electrocardiographic analysis, but the utility of the Epworth is questioned by its minimal relation to clinical, electrocardiographic, or polysomnographic features. C1 [Eiseman, Nathaniel A.; Westover, M. Brandon; Bianchi, Matt T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mietus, Joseph E.] Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol, Boston, MA 02215 USA. [Mietus, Joseph E.] Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep, Boston, MA 02215 USA. [Bianchi, Matt T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang 7,55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org FU Department of Neurology, Massachusetts General Hospital; Pfizer, Inc.; Merck Co.; Harvard/MIT Health Sciences and Technology-Beth Israel Deaconess Medical Center FX The authors thank Scott McKinney, Drs Sydney Cash, Catherine Chu-Shore and Elizabeth Klerman for valuable discussions. We thank Alex Chan and Melissa St Hilaire for advice on support vector machine classification. Dr Bianchi receives funding from the Department of Neurology, Massachusetts General Hospital and the Clinical Investigator Training Program: Harvard/MIT Health Sciences and Technology-Beth Israel Deaconess Medical Center, in collaboration with Pfizer, Inc. and Merck & Co. This funding source had no role in the design, interpretation or publication of this study. This paper represents the work of the authors. This manuscript was not prepared in collaboration with investigators of the Sleep Heart Health Study and does not necessarily reflect the opinions or views of the Sleep Heart Health Study or the NHLBI. NR 33 TC 17 Z9 18 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD FEB PY 2012 VL 21 IS 1 BP 101 EP 112 DI 10.1111/j.1365-2869.2011.00935.x PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 879MB UT WOS:000299332300014 PM 21752133 ER PT J AU Coca, SG Jammalamadaka, D Sint, K Philbrook, HT Shlipak, MG Zappitelli, M Devarajan, P Hashim, S Garg, AX Parikh, CR AF Coca, Steven G. Jammalamadaka, Divakar Sint, Kyaw Philbrook, Heather Thiessen Shlipak, Michael G. Zappitelli, Michael Devarajan, Prasad Hashim, Sabet Garg, Amit X. Parikh, Chirag R. CA Translational Res Invest Biomarker TI Preoperative proteinuria predicts acute kidney injury in patients undergoing cardiac surgery SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; ACUTE-RENAL-FAILURE; RISK-FACTORS; DISEASE; COHORT; SCORE; STRATIFICATION; ALBUMINURIA; MORTALITY; OUTCOMES AB Objective: The study objective was to examine the utility of using proteinuria in preoperative risk stratification for acute kidney injury. Acute kidney injury is a common and important complication for patients undergoing cardiac surgery. Proteinuria, which reflects structural damage to the glomeruli or renal tubules, may aid the prediction of acute kidney injury. Methods: The urine albumin to creatinine ratio and dipstick proteinuria concentration were prospectively measured in 1159 patients undergoing cardiac surgery. The cohort was organized into 4 clinical risk categories based on the preoperative urine albumin to creatinine ratio: 10 mg/g or less (<= 1.1 mg/mmol), 11 to 29 mg/g (1.2-3.3 mg/mmol), 30 to 299 mg/g (3.4-33.8 mg/mmol), and 300 mg/g or greater (>= 33.9 mg/mmol). The primary outcome was postoperative acute kidney injury, defined by the Acute Kidney Injury Network stage I criterion (serum creatinine increase >= 50% or >= 0.3 mg/dL; 26.5 mu mol/L). Results: An increase in the incidence of acute kidney injury was noted across the urine albumin to creatinine ratio categories. Adding the urine albumin to creatinine ratio to the clinical model to predict acute kidney injury improved the area under the curve from 0.67 to 0.70 (P < .001), and the continuous net reclassification improvement was 29% (P < .001). The urine albumin to creatinine ratio was also independently associated with the risk of in-hospital dialysis and intensive care unit and hospital lengths of stay. Surgery status and preoperative glomerular filtration rate were effect modifiers; the association was stronger among those undergoing elective surgery and those with an estimated glomerular filtration rate of 45 mL/min/1.73 m(2) or greater. Conclusions: Preoperative proteinuria provides graded stratification risk for acute kidney injury and is an independent predictor of other outcomes in patients undergoing cardiac surgery. (J Thorac Cardiovasc Surg 2012;143:495-502) C1 [Parikh, Chirag R.] Yale Univ, Nephrol Sect, Dept Internal Med, Sch Med, West Haven, CT 06516 USA. [Coca, Steven G.; Sint, Kyaw; Parikh, Chirag R.] VA Connecticut, Clin Epidemiol Res Ctr, West Haven, CT USA. [Philbrook, Heather Thiessen; Garg, Amit X.] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada. [Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Zappitelli, Michael] McGill Univ, Montreal Childrens Hosp, Dept Pediat, Div Nephrol,Hlth Ctr, Montreal, PQ H3H 1P3, Canada. [Devarajan, Prasad] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Hashim, Sabet] Yale Univ, Dept Surg, Sch Med, West Haven, CT 06516 USA. RP Parikh, CR (reprint author), Yale Univ, Nephrol Sect, Dept Internal Med, Sch Med, 950 Campbell Ave,Mail Code 151B,Bldg 35 A,Room 21, West Haven, CT 06516 USA. EM chirag.parikh@yale.edu FU American Heart Association; National Heart, Lung, and Blood Institute [R01HL-085757]; CTSA from National Center for Research Resources [UL1 RR024139] FX The research reported in this article was supported by the American Heart Association Clinical Development award; Grant R01HL-085757 from the National Heart, Lung, and Blood Institute; and CTSA Grant UL1 RR024139 from the National Center for Research Resources. NR 23 TC 30 Z9 33 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD FEB PY 2012 VL 143 IS 2 BP 495 EP 502 DI 10.1016/j.jtcvs.2011.09.023 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 879GP UT WOS:000299318000040 PM 22050987 ER PT J AU Fernandes, TL Protta, TR Fregni, F Neto, RB Pedrinelli, A Camanho, GL Hernandez, AJ AF Fernandes, Tiago Lazzaretti Protta, Thiago Rocha Fregni, Felipe Neto, Raul Bolliger Pedrinelli, Andre Camanho, Gilberto Luis Hernandez, Arnaldo Jose TI Isokinetic muscle strength and knee function associated with double femoral pin fixation and fixation with interference screw in anterior cruciate ligament reconstruction SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY LA English DT Article DE Sports medicine; Anterior cruciate ligament; Injuries; Surgery; Absorbable implants; Bone-patellar tendon-bone graft; Muscle strength; Torque; Single-bundle ID PATELLAR TENDON-BONE; HAMSTRING TENDON; FOLLOW-UP; GRAFT FIXATION; AUTOGRAFTS; REHABILITATION; QUADRICEPS; RETURN; INJURIES; DEFICITS AB Intensive scheduling in sports requires athletes to resume physical activity shortly after injury. The purpose of this study was to investigate early isokinetic muscle strength and knee function on bone-patellar tendon-bone (BPTB) ACL reconstruction with double femoral pin fixation or interference screw technique. A prospective study was conducted from 2008 to 2009, with 48 athletes who received femoral BPTB fixation with interference screw (n = 26) or double pin (n = 22). Clinical (IKDC objective score and hop test) and isokinetic muscle strength (peak torque (PT), PT/body weight and flexion/extension rate (F/E) in 60 and 240A degrees/s) were analyzed at 6 months of follow-up. Analysis at baseline showed no differences between groups before surgery related to age, gender, associated injury, Tegner or Lysholm score; thus showing that groups were similar. During follow-up, however, there were significant differences between the two groups in some of the isokinetic muscle strength: PT/BW 60A degrees/s (Double Pin = 200% +/- A 13% vs. Interference Screw = 253% +/- A 16%*, *P = 0.01); F/E 60A degrees/s (Double Pin = 89% +/- A 29%* vs. Interference Screw = 74% +/- A 12%, *P = 0.04). No statistical differences between groups were observed on IKDC objective score, hop test and complications. The significant muscle strength outcome of the interference screw group found in this study gives initial evidence that this fixation technique is useful for athletes that may need accelerated rehabilitation. Early return to sports ability signaled by isokinetic muscle strength is of clinical relevance as it is one of the main goals for athletes' rehabilitation. III. C1 [Fernandes, Tiago Lazzaretti; Protta, Thiago Rocha; Neto, Raul Bolliger; Pedrinelli, Andre; Camanho, Gilberto Luis; Hernandez, Arnaldo Jose] Univ Sao Paulo, Inst Orthoped & Traumatol, Hosp Clin, Sch Med,FIFA Med Ctr Excellence, Sao Paulo, Brazil. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Fregni, Felipe] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Fernandes, TL (reprint author), Univ Sao Paulo, Inst Orthoped & Traumatol, Hosp Clin, Sch Med,FIFA Med Ctr Excellence, 333 Dr Ovidio Pires de Campos, Sao Paulo, Brazil. EM tiago.lazzaretti@usp.br RI Hernandez, 1083/I-7939-2016; CAMANHO, GILBERTO/K-4011-2016; Fernandes, Tiago/B-9107-2017 OI Hernandez, 1083/0000-0001-8645-3956; Fernandes, Tiago/0000-0002-6665-3608 NR 40 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-2056 EI 1433-7347 J9 KNEE SURG SPORT TR A JI Knee Surg. Sports Traumatol. Arthrosc. PD FEB PY 2012 VL 20 IS 2 BP 275 EP 280 DI 10.1007/s00167-011-1585-y PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 880AP UT WOS:000299376800013 PM 21710112 ER PT J AU Merchant, RM Yang, L Becker, LB Berg, RA Nadkarni, V Nichol, G Carr, BG Mitra, N Bradley, SM Abella, BS Groeneveld, PW AF Merchant, Raina M. Yang, Lin Becker, Lance B. Berg, Robert A. Nadkarni, Vinay Nichol, Graham Carr, Brendan G. Mitra, Nandita Bradley, Steven M. Abella, Benjamin S. Groeneveld, Peter W. CA Amer Heart Assoc Get TI Variability in Case-mix Adjusted In-hospital Cardiac Arrest Rates SO MEDICAL CARE LA English DT Article DE cardiopulmonary resuscitation; heart arrest; resuscitation ID CARDIOPULMONARY-RESUSCITATION; RACIAL VARIATION; CARE; QUALITY; MORTALITY; SURVIVAL; OUTCOMES; TEAMS AB Background: It is unknown how in-hospital cardiac arrest (IHCA) rates vary across hospitals and predictors of variability. Objectives: Measure variability in IHCA across hospitals and determine if hospital-level factors predict differences in case-mix adjusted event rates. Research Design: Get with the Guidelines Resuscitation (GWTG-R) (n = 433 hospitals) was used to identify IHCA events between 2003 and 2007. The American Hospital Association survey, Medicare, and US Census were used to obtain detailed information about GWTG-R hospitals. Participants: Adult patients with IHCA. Measures: Case-mix-adjusted predicted IHCA rates were calculated for each hospital and variability across hospitals was compared. A regression model was used to predict case-mix adjusted event rates using hospital measures of volume, nurse-to-bed ratio, percent intensive care unit beds, palliative care services, urban designation, volume of black patients, income, trauma designation, academic designation, cardiac surgery capability, and a patient risk score. Results: We evaluated 103,117 adult IHCAs at 433 US hospitals. The case-mix adjusted IHCA event rate was highly variable across hospitals, median 1/1000 bed days (interquartile range: 0.7 to 1.3 events/1000 bed days). In a multivariable regression model, case-mix adjusted IHCA event rates were highest in urban hospitals [rate ratio (RR), 1.1; 95% confidence interval (CI), 1.0-1.3; P = 0.03] and hospitals with higher proportions of black patients (RR, 1.2; 95% CI, 1.0-1.3; P = 0.01) and lower in larger hospitals (RR, 0.54; 95% CI, 0.45-0.66; P < 0.0001). Conclusions: Case-mix adjusted IHCA event rates varied considerably across hospitals. Several hospital factors associated with higher IHCA event rates were consistent with factors often linked with lower hospital quality of care. C1 [Merchant, Raina M.; Becker, Lance B.; Carr, Brendan G.; Abella, Benjamin S.] Univ Penn, Dept Emergency Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Yang, Lin; Groeneveld, Peter W.] Univ Penn, Div Gen Internal Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Berg, Robert A.; Nadkarni, Vinay] Univ Penn, Dept Anesthesiol & Crit Care Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Bradley, Steven M.] Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. [Merchant, Raina M.; Mitra, Nandita] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Groeneveld, Peter W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Merchant, RM (reprint author), Univ Penn, Dept Biostat & Epidemiol, 423 Guardian St,1022 Blockley Hall, Philadelphia, PA 19104 USA. EM raina.merchant@uphs.upenn.edu OI Abella, Benjamin/0000-0003-2521-0891 FU Robert Wood Johnson Foundation at the University of Pennsylvania; Institute for Health Technology Studies (Washington, DC) from the National Heart, Lung, and Blood Institute [1-R01-HL086919]; Pennsylvania Department of Health; Department of Veterans Affairs' Health Services Research and Development Service; Philips Healthcare, Seattle, WA; Laerdal Medical, Stavanger, Norway; NIH, Bethesda, MD; Cardiac Science, Bothell, Washington; Laerdal Foundation for Acute Care Medicine, Stavanger, Norway; AHRQ, Bethesda, MD; Resuscitation Outcomes Consortium [NIH U01 HL077863-05]; NHLBI [R21 HL093641-01A1, R01 HL089554-03]; Resynchronization/Defibrillation for Advanced Heart Failure Trial (RAFT) [200211UCT-110607, 1RC2HL101759-01]; Medtronic Foundation; Laerdal Medical Corp, Stavanger, Norway FX Supported by funding from the Robert Wood Johnson Foundation Clinical Scholars program at the University of Pennsylvania (Merchant). This study was also supported by an unrestricted grant from the Institute for Health Technology Studies (Washington, DC) and Grant 1-R01-HL086919 from the National Heart, Lung, and Blood Institute. This study was also funded, in part, under a grant from the Pennsylvania Department of Health, which specifically disclaims responsibility for any analyses, interpretations, or conclusions. Dr Groeneveld was additionally supported by a Research Career Development Award from the Department of Veterans Affairs' Health Services Research and Development Service. None of the above funding sources were involved in the design or conduct of the study, collection, management, analysis, or interpretation of the data, or preparation, review, or approval of the article.; R. M. M., L. Y., S. B. has no conflicts of interest to disclose; L. B.: Speaker honoraria/consultant fees: Philips Healthcare, Seattle, WA. Institutional grant/research support: Philips Healthcare, Seattle, WA; Laerdal Medical, Stavanger, Norway; NIH, Bethesda, MD; Cardiac Science, Bothell, Washington; R. B.: Institutional grant/research support: NIH, Bethesda, MD; V. N.: Institutional grant/research support: Laerdal Foundation for Acute Care Medicine, Stavanger, Norway; NIH, Bethesda, MD; AHRQ, Bethesda, MD. G. N.: Institutional grant/research support: Resuscitation Outcomes Consortium (NIH U01 HL077863-05) 2004 to 2015; Co-PI, Evaluation of Video Self-Instruction in Compressions-Only CPR (Asmund S. Laerdal Foundation for Acute Medicine) 2007 to 2010; PI, Randomized Trial of Hemofiltration After Resuscitation from Cardiac Arrest (NHLBI R21 HL093641-01A1) 2009 to 2011; PI, Randomized Field Trial of Cold Saline IV After Resuscitation from Cardiac Arrest (NHLBI R01 HL089554-03) 2007 to 2012; Co-I, Resynchronization/Defibrillation for Advanced Heart Failure Trial (RAFT) (200211UCT-110607) 2003 to 2010; Co-I, Novel Methods of Measuring Health Disparities (1RC2HL101759-01) 2009 to 2011; Co-I, Cascade Cardiac Resuscitation System (Medtronic Foundation) 2010 to 2015; PI, Research Collaborator: Gambro Renal Inc., Lakewood, CO, Sotera Wireless, San Diego, CA, Lifebridge Medizintechnik AG, Ampfing, Germany, Other: Chair, AHA Executive Database Steering Committee; Chair, Mission: Lifeline EMS Task Force, Co-Chair, AHA Resuscitation Science Symposium Planning Committee; Member, AHA Advanced Cardiac Life Support Subcommittee; Member, AHA Epidemiology and Statistics Committee; Member, Pacific Mountain Affiliate Board of Directors, American Heart Association, Received travel reimbursement, AHA. B. C.: Institutional grant/research support: NIH, AHRQ. B. A.: Speaker honoraria/consultant fees: Philips Healthcare, Seattle, WA; Medivance Corporation, Louisville, CO. Institutional grant/research support: Philips Healthcare, Andover, MA; Doris Duke Foundation, New York City, NY; American Heart Association, Dallas, TX; NIH, Bethesda, MD. In-kind research support: Laerdal Medical Corp, Stavanger, Norway. P. G.: Federal employee. NR 33 TC 20 Z9 20 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD FEB PY 2012 VL 50 IS 2 BP 124 EP 130 DI 10.1097/MLR.0b013e31822d5d17 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 879FR UT WOS:000299315600003 PM 22249921 ER PT J AU Hynes, DM Stroupe, KT Fischer, MJ Reda, DJ Manning, W Browning, MM Huo, ZP Saban, K Kaufman, JS AF Hynes, Denise M. Stroupe, Kevin T. Fischer, Michael J. Reda, Domenic J. Manning, Willard Browning, Margaret M. Huo, Zhiping Saban, Karen Kaufman, James S. CA ESRD Cost Study Grp TI Comparing VA and Private Sector Healthcare Costs for End-stage Renal Disease SO MEDICAL CARE LA English DT Article DE costs; outcomes; end-stage renal disease; dialysis; Veterans; Medicare ID CLINICAL COMORBIDITY INDEX; OF-LIFE INSTRUMENT; WELL-BEING SCALE; KIDNEY-DISEASE; DIALYSIS FACILITIES; QUALITY; HEMODIALYSIS; MORTALITY; VETERANS; MEDICARE AB Background: Healthcare for end-stage renal disease (ESRD) is intensive, expensive, and provided in both the public and private sector. Using a societal perspective, we examined healthcare costs and health outcomes for Department of Veterans Affairs (VA) ESRD patients comparing those who received hemodialysis care at VA versus private sector facilities. Methods: Dialysis patients were recruited from 8 VA medical centers from 2001 through 2003 and followed for 12 months in a prospective cohort study. Patient demographics, clinical characteristics, quality of life, healthcare use, and cost data were collected. Healthcare data included utilization (VA), claims (Medicare), and patient self-report. Costs included VA calculated costs, Medicare dialysis facility reports and reimbursement rates, and patient self-report. Multivariable regression was used to compare costs between patients receiving dialysis at VA versus private sector facilities. Results: The cohort comprised 334 patients: 170 patients in the VA dialysis group and 164 patients in the private sector group. The VA dialysis group had more comorbidities at baseline, outpatient and emergency visits, prescriptions, and longer hospital stays; they also had more conservative anemia management and lower baseline urea reduction ratio (67% vs. 72%; P < 0.001), although levels were consistent with guidelines (Kt/V >= 1.2). In adjusted analysis, the VA dialysis group had $36,431 higher costs than those in the private sector dialysis group (P < 0.001). Conclusions: Continued research addressing costs and effectiveness of care across public and private sector settings is critical in informing health policy options for patients with complex chronic illnesses such as ESRD. C1 [Hynes, Denise M.; Stroupe, Kevin T.; Browning, Margaret M.] Edward Hines Jr VA Hosp, VA Informat Resource Ctr, Hines, IL 60141 USA. [Hynes, Denise M.] Univ Illinois, Coll Med, Dept Med, Chicago, IL USA. [Stroupe, Kevin T.; Reda, Domenic J.] Edward Hines Jr VA Hosp, VA Cooperat Studies Program Coordinating Ctr, Hines, IL 60141 USA. [Stroupe, Kevin T.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. [Fischer, Michael J.] Univ Illinois, Coll Med, Dept Med Nephrol, Chicago, IL USA. [Fischer, Michael J.] Univ Illinois, Sch Publ Hlth, Jesse Brown VA Med Ctr, Chicago, IL USA. [Reda, Domenic J.] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL USA. [Manning, Willard] Univ Chicago, Chicago, IL 60637 USA. [Saban, Karen] Loyola Univ Chicago, Niehoff Sch Nursing, Maywood, IL USA. [Kaufman, James S.] VA Boston Healthcare Syst, Boston, MA USA. [Kaufman, James S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Hynes, DM (reprint author), Edward Hines Jr VA Hosp, VA Informat Resource Ctr, 5000S 5th Ave,151V, Hines, IL 60141 USA. EM denise.hynes@va.gov RI Saban, Karen/H-4837-2011 OI Saban, Karen/0000-0001-5767-5453 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [ECI 20-016]; VA Research Career Scientist Award; VA Career Development Award; Amgen; Genzyme; Roche FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (Project Number: ECI 20-016). Dr Hynes was also supported by a VA Research Career Scientist Award and Dr Fisher was supported by a VA Career Development Award during part of the study. Dr Kaufman has received grants and honoraria from Amgen, Genzyme, and Roche. NR 44 TC 7 Z9 7 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 2012 VL 50 IS 2 BP 161 EP 170 DI 10.1097/MLR.0b013e31822dcf15 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 879FR UT WOS:000299315600008 PM 21945972 ER PT J AU Lapham, GT Achtmeyer, CE Williams, EC Hawkins, EJ Kivlahan, DR Bradley, KA AF Lapham, Gwen T. Achtmeyer, Carol E. Williams, Emily C. Hawkins, Eric J. Kivlahan, Daniel R. Bradley, Katharine A. TI Increased Documented Brief Alcohol Interventions With a Performance Measure and Electronic Decision Support SO MEDICAL CARE LA English DT Article DE alcoholism and addictive behaviors; performance measurement; veterans; preventive care; implementation research ID PRIMARY-HEALTH-CARE; BEHAVIORAL-COUNSELING INTERVENTIONS; COMPUTERIZED CLINICAL REMINDERS; BRIEF PHYSICIAN ADVICE; GENERAL-PRACTITIONERS; PREVENTIVE-SERVICES; COST-EFFECTIVENESS; PUBLIC-HEALTH; VETERANS; PATIENT AB Background: Alcohol screening and brief interventions (BIs) are ranked the third highest US prevention priority, but effective methods of implementing BI into routine care have not been described. Objectives: This study evaluated the prevalence of documented BI among Veterans Affairs (VA) outpatients with alcohol misuse before, during, and after implementation of a national performance measure (PM) linked to incentives and dissemination of an electronic clinical reminder (CR) for BI. Methods: VA outpatients were included in this study if they were randomly sampled for national medical record reviews and screened positive for alcohol misuse (Alcohol Use Disorders Identification Test-Consumption score >= 5) between July 2006 and September 2008 (N = 6788). Consistent with the PM, BI was defined as documented advice to reduce or abstain from drinking plus feedback linking drinking to health. The prevalence of BI was evaluated among outpatients who screened positive for alcohol misuse during 4 successive phases of BI implementation: baseline year (n = 3504), after announcement (n = 753) and implementation (n = 697) of the PM, and after CR dissemination (n = 1834), unadjusted and adjusted for patient characteristics. Results: Among patients with alcohol misuse, the adjusted prevalence of BI increased significantly over successive phases of BI implementation, from 5.5% (95% CI 4.1%-7.5%), 7.6% (5.6%-10.3%), 19.1% (15.4%-23.7%), to 29.0% (25.0%-33.4%) during the baseline year, after PM announcement, PM implementation, and CR dissemination, respectively (test for trend P < 0.001). Conclusions: A national PM supported by dissemination of an electronic CR for BI was associated with meaningful increases in the prevalence of documented brief alcohol interventions. C1 [Lapham, Gwen T.; Achtmeyer, Carol E.; Williams, Emily C.; Hawkins, Eric J.; Kivlahan, Daniel R.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Hawkins, Eric J.; Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA 98101 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. [Bradley, Katharine A.] Univ Washington, Hlth Serv, Seattle, WA 98195 USA. RP Lapham, GT (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way, Seattle, WA 98101 USA. EM Gwendolyn.Lapham@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service; Veterans Affairs Substance Use Disorders Quality Enhancement Research Initiative [SUB 98-000] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service. The article was specifically produced with support from the Veterans Affairs Substance Use Disorders Quality Enhancement Research Initiative (SUB 98-000). NR 50 TC 51 Z9 51 U1 5 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD FEB PY 2012 VL 50 IS 2 BP 179 EP 187 DI 10.1097/MLR.0b013e3181e35743 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 879FR UT WOS:000299315600010 PM 20881876 ER PT J AU Taff, HT Nett, JE Andes, DR AF Taff, Heather T. Nett, Jeniel E. Andes, David R. TI Comparative analysis of Candida biofilm quantitation assays SO MEDICAL MYCOLOGY LA English DT Article DE Candida; biofilm; assay ID IN-VITRO; ALBICANS; QUANTIFICATION; INFECTION; GROWTH; SURFACES; VIVO AB Candida grows on devices producing treatment resistant biofilms. A key tool for the study of biofilms includes an accurate assessment of viable cell growth. This study systematically tested seven techniques, among which the XTT assay provided the most reproducible, accurate, and efficient method for the quantitative estimation of C. albicans biofilms. C1 [Taff, Heather T.; Nett, Jeniel E.; Andes, David R.] Univ Wisconsin, Dept Microbiol, Madison, WI 53706 USA. [Taff, Heather T.; Nett, Jeniel E.; Andes, David R.] Univ Wisconsin, Dept Immunol, Madison, WI 53706 USA. [Andes, David R.] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Nett, Jeniel E.; Andes, David R.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Andes, DR (reprint author), 5211 UW Med Fdn Centennial Bldg,1685 Highland Ave, Madison, WI 53705 USA. EM dra@medicine.wisc.edu FU National Institutes of Health [RO1 AI073289-01] FX The authors would like to thank A. Mitchell and C. Nobile for the strains. This work was supported by the National Institutes of Health (RO1 AI073289-01). NR 25 TC 24 Z9 24 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD FEB PY 2012 VL 50 IS 2 BP 214 EP 218 DI 10.3109/13693786.2011.580016 PG 5 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 876FS UT WOS:000299093600014 PM 21539503 ER PT J AU Brainard, LL Beckwith, JG Chu, JJ Crisco, JJ Mcallister, TW Duhaime, AC Maerlender, AC Greenwald, RM AF Brainard, Lindley L. Beckwith, Jonathan G. Chu, Jeffrey J. Crisco, Joseph J. Mcallister, Thomas W. Duhaime, Ann-Christine Maerlender, Arthur C. Greenwald, Richard M. TI Gender Differences in Head Impacts Sustained by Collegiate Ice Hockey Players SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE CONCUSSION; BRAIN INJURY; SPORTS; ICE HOCKEY; GENDER; HEAD IMPACT ID HIGH-SCHOOL FOOTBALL; TRAUMATIC BRAIN-INJURIES; PROFESSIONAL FOOTBALL; UNITED-STATES; RECURRENT CONCUSSION; EPIDEMIOLOGY; ACCELERATION; ASSOCIATION; SPORTS; RECOMMENDATIONS AB BRAINARD, L. L., J. G. BECKWITH, J. J. CHU, J. J. CRISCO, T. W. MCALLISTER, A. DUHAIME, A. C. MAERLENDER, and R. M. GREENWALD. Gender Differences in Head Impacts Sustained by Collegiate Ice Hockey Players. Med. Sci. Sports Exerc., Vol. 44, No. 2, pp. 297-304, 2012. Purpose: This study aimed to quantify the frequency, magnitude, and location of head impacts sustained by male and female collegiate ice hockey players during two seasons of play. Methods: During two seasons, 88 collegiate athletes (51 females, 37 males) on two female and male National Collegiate Athletic Association varsity ice hockey teams wore instrumented helmets. Each helmet was equipped with six single-axis accelerometers and a miniature data acquisition system to capture and record head impacts sustained during play. Data collected from the helmets were postprocessed to compute linear and rotational accelerations of the head as well as impact location. The head impact exposure data (frequency, location, and magnitude) were then compared between genders. Results: Female hockey players experienced a significantly lower (P < 0.001) number of impacts per athlete exposure than males (females = 1.7 +/- 0.7, males = 2.9 +/- 1.2). The frequency of impacts by location was the same between genders (P > 0.278) for all locations except the right side of the head, where males received fewer impacts than females (P = 0.031). Female hockey players were 1.1 times more likely than males to sustain an impact less than 50g, whereas males were 1.3 times more likely to sustain an impact greater than 100g. Similarly, males were 1.9 times more likely to sustain an impact with peak rotational acceleration greater than 5000 rad.s(-2) and 3.5 times more likely to sustain an impact greater than 10,000 rad.s(-2). Conclusions: Although the incidence of concussion has typically been higher for female hockey players than male hockey players, female players sustain fewer impacts and impacts resulting in lower head acceleration than males. Further study is required to better understand the intrinsic and extrinsic risk factors that lead to higher rates of concussion for females that have been previously reported. C1 [Brainard, Lindley L.; Beckwith, Jonathan G.; Chu, Jeffrey J.; Greenwald, Richard M.] Simbex, Lebanon, NH 03766 USA. [Crisco, Joseph J.] Brown Univ, Bioengn Lab, Dept Orthoped, Alpert Med Sch, Providence, RI 02912 USA. [Crisco, Joseph J.] Rhode Isl Hosp, Providence, RI USA. [Mcallister, Thomas W.; Maerlender, Arthur C.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03756 USA. [Duhaime, Ann-Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Duhaime, Ann-Christine] Harvard Univ, Sch Med, Boston, MA USA. [Greenwald, Richard M.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Beckwith, JG (reprint author), Simbex, 10 Water St,Suite 410, Lebanon, NH 03766 USA. EM jbeckwith@simbex.com FU National Institute for Child Health and Human Development at the National Institutes of Health [R01HD048638]; National Operating Committee on Standards for Athletic Equipment FX The research for this study was supported by the National Institute for Child Health and Human Development at the National Institutes of Health (grant no. R01HD048638) and the National Operating Committee on Standards for Athletic Equipment. Joseph J. Crisco, Richard M. Greenwald, Jeffrey J. Chu, and Simbex have a financial interest in the instruments (HIT System, Sideline Response System (Riddell, Inc.)) that were used to collect the data reported in this study. NR 42 TC 29 Z9 29 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD FEB PY 2012 VL 44 IS 2 BP 297 EP 304 DI 10.1249/MSS.0b013e31822b0ab4 PG 8 WC Sport Sciences SC Sport Sciences GA 879FY UT WOS:000299316300016 PM 21716150 ER PT J AU Freeman, GJ Sharpe, AH AF Freeman, Gordon J. Sharpe, Arlene H. TI A new therapeutic strategy for malaria: targeting T cell exhaustion SO NATURE IMMUNOLOGY LA English DT Editorial Material ID CHRONIC VIRAL-INFECTION; PD-1; BLOCKADE; CANCER; TIM-3; LAG-3 AB Boosting immune responses during malaria remains a challenge. Overcoming T cell exhaustion by blocking coinhibitory receptors offers a promising lead. C1 [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, Boston, MA 02115 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, 44 Binney St, Boston, MA 02115 USA. EM gordon_freeman@dfci.harvard.edu FU NIAID NIH HHS [R01 AI089955] NR 15 TC 11 Z9 11 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2012 VL 13 IS 2 BP 113 EP 115 DI 10.1038/ni.2211 PG 4 WC Immunology SC Immunology GA 879FL UT WOS:000299315000005 PM 22261959 ER PT J AU van Gils, JM Derby, MC Fernandes, LR Ramkhelawon, B Ray, TD Rayner, KJ Parathath, S Distel, E Feig, JL Alvarez-Leite, JI Rayner, AJ McDonald, TO O'Brien, KD Stuart, LM Fisher, EA Lacy-Hulbert, A Moore, KJ AF van Gils, Janine M. Derby, Merran C. Fernandes, Luciana R. Ramkhelawon, Bhama Ray, Tathagat D. Rayner, Katey J. Parathath, Sajesh Distel, Emilie Feig, Jessica L. Alvarez-Leite, Jacqueline I. Rayner, Alistair J. McDonald, Thomas O. O'Brien, Kevin D. Stuart, Lynda M. Fisher, Edward A. Lacy-Hulbert, Adam Moore, Kathryn J. TI The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques SO NATURE IMMUNOLOGY LA English DT Article ID MONOCYTE-DERIVED CELLS; ISCHEMIA-REPERFUSION INJURY; DEFICIENT MICE; OXIDIZED LDL; LYMPH-NODES; FOAM CELLS; IN-VIVO; INFLAMMATION; EXPRESSION; MIGRATION AB Atherosclerotic plaque formation is fueled by the persistence of lipid-laden macrophages in the artery wall. The mechanisms by which these cells become trapped, thereby establishing chronic inflammation, remain unknown. Here we found that netrin-1, a neuroimmune guidance cue, was secreted by macrophages in human and mouse atheroma, where it inactivated the migration of macrophages toward chemokines linked to their egress from plaques. Acting via its receptor, UNC5b, netrin-1 inhibited the migration of macrophages directed by the chemokines CCL2 and CCL19, activation of the actin-remodeling GTPase Rac1 and actin polymerization. Targeted deletion of netrin-1 in macrophages resulted in much less atherosclerosis in mice deficient in the receptor for low-density lipoprotein and promoted the emigration of macrophages from plaques. Thus, netrin-1 promoted atherosclerosis by retaining macrophages in the artery wall. Our results establish a causative role for negative regulators of leukocyte migration in chronic inflammation. C1 [van Gils, Janine M.; Ramkhelawon, Bhama; Ray, Tathagat D.; Rayner, Katey J.; Parathath, Sajesh; Distel, Emilie; Feig, Jessica L.; Rayner, Alistair J.; Fisher, Edward A.; Moore, Kathryn J.] NYU, Sch Med, Marc & Ruti Bell Vasc Biol & Dis Program, Leon H Charney Div Cardiol,Dept Med, New York, NY 10003 USA. [Derby, Merran C.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Fernandes, Luciana R.; Alvarez-Leite, Jacqueline I.] Univ Fed Minas Gerais, Dept Biochem & Immunol, Belo Horizonte, MG, Brazil. [McDonald, Thomas O.; O'Brien, Kevin D.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Stuart, Lynda M.; Lacy-Hulbert, Adam] Harvard Univ, Sch Med, Dept Pediat, Program Dev Immunol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Fisher, Edward A.; Moore, Kathryn J.] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. RP Moore, KJ (reprint author), NYU, Sch Med, Marc & Ruti Bell Vasc Biol & Dis Program, Leon H Charney Div Cardiol,Dept Med, New York, NY 10003 USA. EM kathryn.moore@nyumc.org RI Rayner, Katey/K-8914-2012; OI Lacy-Hulbert, Adam/0000-0003-2162-0156; Moore, kathryn/0000-0003-2505-2547; Fisher, Edward/0000-0001-9802-143X FU American Heart Association [0655840T, 09POST2080250]; US National Institutes of Health [RC1HL100815, R01HL084312]; Heart and Stroke Foundation of Canada; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [01558/2007-6] FX We thank J. Goss and W. Groot for technical support; M. Tessier-Lavigne (Stanford University) for Ntn1+/- mice; and T. Kinane (Massachusetts General Hospital) for anti-UNC5b antiserum. Supported by the American Heart Association (0655840T to K. M. and 09POST2080250 to J. M. v. G.), the US National Institutes of Health (RC1HL100815 to K. J. M. and R01HL084312 to E. A. F.), the Heart and Stroke Foundation of Canada (K. J. R.) and the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (01558/2007-6 to L. R. F. and J. I. A.-L.). NR 40 TC 110 Z9 111 U1 1 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2012 VL 13 IS 2 BP 136 EP 143 DI 10.1038/ni.2205 PG 8 WC Immunology SC Immunology GA 879FL UT WOS:000299315000010 PM 22231519 ER PT J AU Berdichevsky, Y Dzhala, V Mail, M Staley, KJ AF Berdichevsky, Yevgeny Dzhala, Volodymyr Mail, Michelle Staley, Kevin J. TI Interictal spikes, seizures and ictal cell death are not necessary for post-traumatic epileptogenesis in vitro SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Epilepsy; Epileptogenesis; Traumatic brain injury; Phenytoin; Neuronal death; Activity; Interictal; Ictal ID TEMPORAL-LOBE EPILEPSY; ORGANOTYPIC SLICE CULTURES; INDUCED STATUS EPILEPTICUS; HEAD-INJURY; ANTIEPILEPTIC DRUGS; DENTATE GYRUS; CYTO-TOXICITY; GRANULE CELLS; AXONAL INJURY; BRAIN-INJURY AB Clinical studies indicate that phenytoin prevents acute post-traumatic seizures but not subsequent post-traumatic epilepsy. We explored this phenomenon using organotypic hippocampal slice cultures as a model of severe traumatic brain injury. Hippocampal slices were cultured for up to eight weeks, during which acute and chronic electrical recordings revealed a characteristic evolution of spontaneous epileptiform discharges, including interictal spikes, seizure activity and electrical status epilepticus. Cell death exhibited an early peak immediately following slicing, and a later secondary peak that coincided with the peak of seizure-like activity. The secondary peak in neuronal death was abolished by either blockade of glutamatergic transmission with kynurenic acid or by elimination of ictal activity and status epilepticus with phenytoin. Withdrawal of kynurenic acid or phenytoin was followed by a sharp increase in spontaneous seizure activity. Phenytoin's anticonvulsant and neuroprotective effects failed after four weeks of continuous administration. These data support the clinical findings that after brain injury, anticonvulsants prevent seizures but not epilepsy or the development of anticonvulsant resistance. We extend the clinical data by showing that secondary neuronal death is correlated with ictal but not interictal activity, and that blocking all three of these sequelae of brain injury does not prevent epileptogenesis in this in vitro model. (C) 2011 Elsevier Inc. All rights reserved. C1 [Berdichevsky, Yevgeny; Dzhala, Volodymyr; Mail, Michelle; Staley, Kevin J.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Staley, KJ (reprint author), MGH Neurol, CNY 114,Room 2600,114 16th St, Charlestown, MA 02129 USA. EM kstaley@partners.org FU National Institute of Neurological Disorders and Stroke (NINDS); Epilepsy Foundation (EFA) FX This work was supported by National Institute of Neurological Disorders and Stroke (NINDS) and Epilepsy Foundation (EFA). NR 64 TC 24 Z9 24 U1 0 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD FEB PY 2012 VL 45 IS 2 BP 774 EP 785 DI 10.1016/j.nbd.2011.11.001 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 881QC UT WOS:000299500200012 PM 22115940 ER PT J AU Deo, AJ Cahill, ME Li, SY Goldszer, I Henteleff, R VanLeeuwen, JE Rafalovich, I Gao, RQ Stachowski, EK Sampson, AR Lewis, DA Penzes, P Sweet, RA AF Deo, Anthony J. Cahill, Michael E. Li, Siyu Goldszer, Isaac Henteleff, Ruth VanLeeuwen, Jon-Eric Rafalovich, Igor Gao, Ruoqi Stachowski, Erin K. Sampson, Allan R. Lewis, David A. Penzes, Peter Sweet, Robert A. TI Increased expression of Kalirin-9 in the auditory cortex of schizophrenia subjects: Its role in dendritic pathology SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Endophenotypes; Kalirin; Schizophrenia; Schizoaffective; Auditory cortex; Dendrite ID GDP/GTP EXCHANGE FACTOR; PYRAMIDAL NEURONS; PREFRONTAL CORTEX; POSTSYNAPTIC DENSITY; SPINE MORPHOGENESIS; PLANUM TEMPORALE; HESCHL GYRUS; DBL FAMILY; MECHANISMS; REDUCTION AB Reductions in dendritic arbor length and complexity are among the most consistently replicated changes in neuronal structure in post mortem studies of cerebral cortical samples from subjects with schizophrenia, however, the underlying molecular mechanisms have not been identified. This study is the first to identify an alteration in a regulatory protein which is known to promote both dendritic length and arborization in developing neurons, Kalirin-9. We found Kalirin-9 expression to be paradoxically increased in schizophrenia. We followed up this observation by overexpressing Kalirin-9 in mature primary neuronal cultures, causing reduced dendritic length and complexity. Kalirin-9 overexpression represents a potential mechanism for dendritic changes seen in schizophrenia. Published by Elsevier Inc. C1 [Deo, Anthony J.; Goldszer, Isaac; Henteleff, Ruth; Lewis, David A.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Translat Neurosci Program, Pittsburgh, PA 15213 USA. [Deo, Anthony J.] Univ Pittsburgh, Sch Med, Phys Scientist Training Program, Pittsburgh, PA 15213 USA. [Cahill, Michael E.; VanLeeuwen, Jon-Eric; Rafalovich, Igor; Gao, Ruoqi; Penzes, Peter] Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA. [Li, Siyu; Sampson, Allan R.] Univ Pittsburgh, Dept Stat, Pittsburgh, PA 15213 USA. [Stachowski, Erin K.; Lewis, David A.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15213 USA. [Penzes, Peter] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, Educ & Clin Ctr, VISN Mental Illness Res 4, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Translat Neurosci Program, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu RI Lewis, David/G-4053-2014; Penzes, Peter/L-3987-2016 OI Lewis, David/0000-0002-3225-6778; Penzes, Peter/0000-0001-5449-1640 FU NIH [MH071533, MH084053, MH071316, F31AG031621-01A2, 1F31MH087043]; Doris Duke Charitable Foundation; BMS Foundation; Bristol-Myers Squibb; Curridium Ltd; Pfizer FX This work was supported by the NIH grants MH071533, MH084053 and MH071316. Anthony Deo was supported by a Clinical Research Fellow grant from the Doris Duke Charitable Foundation to the University of Pittsburgh School of Medicine. Michael Cahill is supported by NIH F31AG031621-01A2; Jon VanLeeuwen is supported by NIH 1F31MH087043. Allan R. Sampson is a statistical consultant to Johnson & Johnson Pharmaceutical Research and Development. Dr. Lewis currently receives investigator-initiated research support from the BMS Foundation, Bristol-Myers Squibb, Curridium Ltd and Pfizer and in 2007-2010 served as a consultant in the areas of target identification and validation and new compound development to AstraZeneca, BioLine RX, Bristol-Myers Squibb, Hoffman-Roche, Lilly, Merck, Neurogen, and SK Life Science. The authors thank Josephine Asafu-Adjei for statistical assistance. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institutes of Health, the Department of Veterans Affairs or the United States Government. NR 48 TC 16 Z9 16 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD FEB PY 2012 VL 45 IS 2 BP 796 EP 803 DI 10.1016/j.nbd.2011.11.003 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 881QC UT WOS:000299500200014 PM 22120753 ER PT J AU Linnman, C Beucke, JC Jensen, KB Gollub, RL Kong, J AF Linnman, Clas Beucke, Jan-Carl Jensen, Karin B. Gollub, Randy L. Kong, Jian TI Sex similarities and differences in pain-related periaqueductal gray connectivity SO PAIN LA English DT Article DE Amygdala; Functional connectivity; Gender; Periaqueductal gray (PAG); Psychophysiological interaction; Sex difference ID VENTROMEDIAL MEDULLARY PATHWAY; MEDIAL PREFRONTAL CORTEX; ANGER MANAGEMENT STYLE; RAT CENTRAL NUCLEUS; BRAIN-STEM; PLACEBO ANALGESIA; FUNCTIONAL CONNECTIVITY; AMYGDALOID PROJECTIONS; GENDER-DIFFERENCES; ELECTRICAL-STIMULATION AB This study investigated sex similarities and differences in pain-related functional connectivity in 60 healthy subjects. We used functional magnetic resonance imaging and psychophysiological interaction analysis to investigate how exposure to low vs high experimental pain modulates the functional connectivity of the periaqueductal gray (PAG). We found no sex differences in pain thresholds, and in both men and women, the PAG was more functionally connected with the somatosensory cortex, the supplemental motor area, cerebellum, and thalamus during high pain, consistent with anatomic predictions. Twenty-six men displayed a pain-induced increase in PAG functional connectivity with the amygdala caudate and putamen that was not observed in women. In an extensive literature search, we found that female animals have been largely overlooked when the connections between the PAG and the amygdala have been described, and that women are systematically understudied with regard to endogenous pain inhibition. Our results emphasize the importance of including both male and female subjects when studying basic mechanisms of pain processing, and point toward a possible sex difference in endogenous pain inhibition. (C) 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Linnman, Clas; Beucke, Jan-Carl; Jensen, Karin B.; Gollub, Randy L.; Kong, Jian] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Linnman, Clas] McLean Hosp, PAIN Grp, Belmont, MA 02178 USA. [Linnman, Clas; Beucke, Jan-Carl; Jensen, Karin B.; Gollub, Randy L.; Kong, Jian] Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Linnman, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Suite 2106,75 13th St, Charlestown, MA 02129 USA. EM linnman@nmr.mgh.harvard.edu RI Jensen, Karin/G-6360-2012; OI Linnman, Clas/0000-0001-8449-894X; Gollub, Randy L./0000-0002-9434-4044; Jensen, Karin/0000-0003-2521-3160 FU International Association for the Study of Pain (IASP); Swedish Society for Medical Research (SSMF); Ev. Studienwerk Villigst (Schwerte, Germany); SSMF; Swedish Council for Working Life and Social Research (FAS); National Center for Complimentary and Alternative Medicine (NCCAM) [PO1-AT002048, KO1AT003883, R21AT004497, R01AT006364, R01AT005280, R21AT00949]; National Institute on Drug Abuse (NIDA) [R03AT218317]; National Center for Research Resources (NCRR) [M01-RR-01066, UL1 RR025758-01, P41RR14075] FX C.L. received support from the International Association for the Study of Pain (IASP) Early Career Award and the Swedish Society for Medical Research (SSMF). J.C.B. received support from Ev. Studienwerk Villigst (Schwerte, Germany) and is an ERP scholar of the German National Academic Foundation. K.J. received support from SSMF and the Swedish Council for Working Life and Social Research (FAS). This work was supported by PO1-AT002048 to B.R. from National Center for Complimentary and Alternative Medicine (NCCAM), KO1AT003883 (NCCAM) and R21AT004497 (NCCAM), R03AT218317 from National Institute on Drug Abuse (NIDA), R01AT006364 (NCCAM) to Jian Kong, R01AT005280 (NCCAM) and R21AT00949 (NCCAM) to Randy Gollub, M01-RR-01066 and UL1 RR025758-01 for Clinical Research Center Biomedical Imaging Core from National Center for Research Resources (NCRR), and P41RR14075 for Center for Functional Neuroimaging Technologies (NCRR). The authors have no conflicts of interest. NR 148 TC 32 Z9 37 U1 3 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD FEB PY 2012 VL 153 IS 2 BP 444 EP 454 DI 10.1016/j.pain.2011.11.006 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 879HH UT WOS:000299319800027 PM 22154332 ER PT J AU van Walraven, SM Ball, LM Koopman, HM Switzer, GE Ropes-de Jong, CMH de Jong, A Bredius, RGM Egeler, RM AF van Walraven, S. M. Ball, L. M. Koopman, H. M. Switzer, G. E. Ropes-de Jong, C. M. H. de Jong, A. Bredius, R. G. M. Egeler, R. M. TI Managing a dual roleuexperiences and coping strategies of parents donating haploidentical G-CSF mobilized peripheral blood stem cells to their children SO PSYCHO-ONCOLOGY LA English DT Article DE childhood cancer; parent donor; experience; coping mechanisms; oncology; haploidentical stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; ACUTE-LEUKEMIA; FOLLOW-UP; DONORS; DISTRESS; CONSENT; PATTERNS; NEEDS AB Hematopoietic stem cell transplantation is an effective therapy for life-threatening hematological diseases. Parents may be asked to donate hematopoietic stem cells for their child when no compatible related or unrelated donor is available. Objective: Parents donating G-CSF mobilized peripheral blood stem cells simultaneously and uniquely fulfill the dual role of donor and caregiver for their ill child. The experiences of both sibling and unrelated stem cell donors have been extensively reported but not those of parental donors. Methods: We therefore undertook a study specifically to investigate the experiences and coping strategies of parental stem cell donors. In-depth qualitative interviews were conducted with 13 parental donors, which were subsequently transcribed and subjected to thematic analysis. In addition, parental coping was assessed utilizing the Utrecht Coping List. Results: Qualitative analyses revealed four main thematic categories describing the way parental stem cell donation was experienced, namely 'Hope and Fear', 'Need for Information', 'Do Anything for your Child' and 'Transplant Outcome' In addition parents noted similar difficulties which were unrelated to their specific role as a donor, for example they felt socially isolated. Conclusions: Individual information for the parents needs to address not only the transplantation procedure but particularly those aspects related to the donation process. We feel there is a need for a protocol specifically designed to support and coach parental donors. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [van Walraven, S. M.; Ball, L. M.; Ropes-de Jong, C. M. H.; Bredius, R. G. M.; Egeler, R. M.] Leiden Univ, Med Ctr, Dept Pediat, NL-2333 ZA Leiden, Netherlands. [Koopman, H. M.] Leiden Univ, Med Ctr, Dept Med Psychol, NL-2333 ZA Leiden, Netherlands. [Switzer, G. E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Switzer, G. E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Switzer, G. E.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA USA. [Switzer, G. E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ & Promot, Pittsburgh, PA USA. [de Jong, A.] Hgsk Utrecht, Utrecht, Netherlands. RP van Walraven, SM (reprint author), Leiden Univ, Med Ctr, Dept Pediat, Albinusdreef 2,J6-S-221, NL-2333 ZA Leiden, Netherlands. EM s.m.van_walraven@lumc.nl NR 39 TC 6 Z9 6 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 IS 2 BP 168 EP 175 DI 10.1002/pon.1885 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 880NX UT WOS:000299415200008 PM 22271537 ER PT J AU Siddiqui, A Dreyer, KJ Gupta, S AF Siddiqui, Adeel Dreyer, Keith Jay Gupta, Supriya TI Meaningful Use: A Call to Arms SO ACADEMIC RADIOLOGY LA English DT Article DE Meaningful use; CMS; electronic health record (EHR); health information technology (HIT) clinical workflow; productivity; incentive payments; exclusions ID ELECTRONIC HEALTH RECORDS AB The benefits of an interactive online world have affected the way we purchase products and plan our vacations. It is only a matter of time before consumers start demanding health care with the same convenience that comes with booking an airline flight or managing a bank account. The health care industry itself requires periodic and mandatory data analysis for outcome analysis, clinical benchmarking, quality improvement, forming guidelines, and making decisions. The federal government and health care community have been working together to come up with more robust and cost-effective health care informatics solutions. Meaningful use (MU) intends to establish a new standard for health care informatics in the United States. The term "meaningful use implies that health care information and technology systems not just exist, but also serve as an integral,part;of physician and hospital workflow; leading to cost savings as well as improved outcomes. Under this concept, the federal government is offering maximum incentive payments of up to $44,000 per physician (including radiologists) if they can meet all the requirements as laid down in the MU measures. Unfortunately, penalties will kick in if physicians are not compliant with MU by 2015. This will be done in at least three stages, with Stage 1 already in effect (as of January 3, 2011). This will be the first in a series of articles outlining MU and What is in store for radiology. We will go in depth about who is eligible, and how the payment schedule is set up. We will break down the core and menu set measures to suggest what can be excluded by most radiologists. We will also go through some case studies and examine what lies in store for radiology. C1 [Siddiqui, Adeel] Beth Israel Deaconess Med Ctr, Dept Radiol, New York, NY 10003 USA. [Dreyer, Keith Jay] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gupta, Supriya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Abdominal Imaging, Boston, MA USA. RP Siddiqui, A (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, New York, NY 10003 USA. EM adeelmu@hotmail.com NR 14 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 2012 VL 19 IS 2 BP 221 EP 228 DI 10.1016/j.acra.2011.11.008 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 878HC UT WOS:000299245100014 PM 22212424 ER PT J AU Bowling, CB O'Hare, AM AF Bowling, C. Barrett O'Hare, Ann M. TI Managing Older Adults With CKD: Individualized Versus Disease-Based Approaches SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Elderly; disease oriented; individualized; patient centered; kidney disease ID CHRONIC KIDNEY-DISEASE; RANDOMIZED CONTROLLED-TRIALS; MULTIPLE CHRONIC CONDITIONS; GLOMERULAR-FILTRATION-RATE; MORTALITY RISK; COGNITIVE IMPAIRMENT; PRACTICE GUIDELINES; STARTING DIALYSIS; ELDERLY PERSONS; UNITED-STATES AB The last decade has seen the evolution and ongoing refinement of a disease-oriented approach to chronic kidney disease (CKD). Disease-oriented models of care assume a direct causal association between observed signs and symptoms and underlying disease pathophysiologic processes. Treatment plans target underlying disease mechanisms with the goal of improving disease-related outcomes. Because average glomerular filtrate rates tend to decrease with age, CKD becomes increasingly prevalent with advancing age and those who meet criteria for CKD are disproportionately elderly. However, several features of geriatric populations may limit the utility of disease-oriented models of care. In older adults, complex comorbid conditions and geriatric syndromes are common; signs and symptoms often do not reflect a single underlying pathophysiologic process; there can be substantial heterogeneity in life expectancy, functional status, and health priorities; and information about the safety and efficacy of recommended interventions often is lacking. For all these reasons, geriatricians have tended to favor an individualized patient-centered model of care over more traditional disease-based approaches. An individualized approach prioritizes patient preferences and embraces the notion that observed signs and symptoms often do not reflect a single unifying disease process and instead reflect the complex interplay between many different factors. This approach emphasizes modifiable outcomes that matter to the patient. Prognostic information related to these and other outcomes generally is used to shape rather than dictate treatment decisions. We argue that an individualized patient-centered approach to care may have more to offer than a traditional disease-based approach to CKD in many older adults. Am J Kidney Dis. 59(2):293-302. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Bowling, C. Barrett] Univ Alabama, Med Ctr, Dept Vet Affairs, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL 35294 USA. [Bowling, C. Barrett] Univ Alabama, Dept Med, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. [O'Hare, Ann M.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [O'Hare, Ann M.] Univ Washington, Dept Med, Seattle, WA USA. RP O'Hare, AM (reprint author), 1160 S Columbian Way,111J RDU, Seattle, WA 98108 USA. EM ann.ohare@va.gov FU National Institute on Aging; Birmingham/Atlanta Geriatric Research Education and Clinical Center; John A. Hartford Foundation/Southeast Center of Excellence in Geriatric Medicine FX Support was through a Beeson Career Development Award from the National Institute on Aging to Dr O'Hare and the Birmingham/Atlanta Geriatric Research Education and Clinical Center Special Fellowship in Advanced Geriatrics and John A. Hartford Foundation/Southeast Center of Excellence in Geriatric Medicine to Dr Bowling. NR 55 TC 40 Z9 43 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2012 VL 59 IS 2 BP 293 EP 302 DI 10.1053/j.ajkd.2011.08.039 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 879GK UT WOS:000299317500021 PM 22189037 ER PT J AU Stineman, MG Henry-Sanchez, JT Kurichi, JE Pan, Q Xie, DW Saliba, D Zhang, Z Streim, JE AF Stineman, Margaret G. Henry-Sanchez, John T. Kurichi, Jibby E. Pan, Qiang Xie, Dawei Saliba, Debra Zhang, Zi Streim, Joel E. TI Staging Activity Limitation and Participation Restriction in Elderly Community-Dwelling Persons According to Difficulties in Self-Care and Domestic Life Functioning SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Independent Living; Aging; Daily Living Activities; ICF ID HOME ACCESSIBILITY FEATURES; SKILLED NURSING FACILITIES; PHYSICAL INDEPENDENCE; OLDER PERSONS; DISABILITY; REHABILITATION; VALIDITY; PATIENT; HEALTH; ICF AB Stineman MG, Henry-Sanchez JT, Kurichi JE, Pan Q, Xie D, Saliba D, Zhang Z, Streim JE: Staging activity limitation and participation restriction in elderly community-dwelling persons according to difficulties in self-care and domestic life functioning. Am J Phys Med Rehabil 2012; 91: 126-140. Objective: This study aimed to describe the conceptual foundation and development of an activity limitation and participation restriction staging system for community-dwelling people 70 yrs or older according to the severity and types of self-care (activities of daily living [ADLs]) and domestic life (instrumental ADLs (IADLs)) limitations experienced. Design: Data from the second Longitudinal Study of Aging (N = 9447) were used to develop IADL stages through the analyses of self- and proxy-reported difficulties in performing IADLs. An analysis of activity limitation profiles identified hierarchical thresholds of difficulty that defined each stage. IADL stages are combined with ADL stages to profile status for independent living. Results: IADL stages define five ordered thresholds of increasing activity limitations and a "not relevant'' stage for those who normally have someone else do those activities. Approximately 42% of the population experience IADL limitations. To achieve a stage, a person must meet or exceed stage-specific thresholds of retained functioning defined for each activity. Combined ADL and IADL stages define 29 patterns of activity limitations expressing the individual's potential for participating in life situations pertinent to self- care and independent community life. Conclusions: ADL and IADL stages can serve to distinguish between groups of people according to both severity and the types of limitations experienced during home or outpatient assessments, in population surveillance, and in research. C1 [Stineman, Margaret G.; Kurichi, Jibby E.; Pan, Qiang; Xie, Dawei; Zhang, Zi] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Stineman, Margaret G.; Henry-Sanchez, John T.] Univ Penn, Dept Phys Med & Rehabil, Perelman Sch Med, Philadelphia, PA 19104 USA. [Saliba, Debra] Univ Calif Los Angeles, Greater Los Angeles VA GRECC, Jewish Home Borun Ctr Gerontol Res, RAND, Los Angeles, CA USA. [Streim, Joel E.] Univ Penn, Geriatr Psychiat Sect, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Streim, Joel E.] Philadelphia Vet Affairs Med Ctr, VISN MIRECC 4, Philadelphia, PA USA. RP Stineman, MG (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Dept Biostat & Epidemiol, 423 Guardian Dr,904 Blockley Hall, Philadelphia, PA 19104 USA. FU technical panel from the grant Impairment Activity Staging [AG032420-01A1] FX We thank the members of the technical panel from the grant Impairment Activity Staging (AG032420-01A1). NR 51 TC 13 Z9 13 U1 7 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD FEB PY 2012 VL 91 IS 2 BP 126 EP 140 DI 10.1097/PHM.0b013e318241200d PG 15 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 879HX UT WOS:000299321400006 PM 22248806 ER PT J AU Wong, MC van Diepen, JA Hu, LH Guigas, B de Boer, HC van Puijvelde, GH Kuiper, J van Zonneveld, AJ Shoelson, SE Voshol, PJ Romijn, JA Havekes, LM Tamsma, JT Rensen, PCN Hiemstra, PS Berbee, JFP AF Wong, Man C. van Diepen, Janna A. Hu, Lihui Guigas, Bruno de Boer, Hetty C. van Puijvelde, Gijs H. Kuiper, Johan van Zonneveld, Anton J. Shoelson, Steven E. Voshol, Peter J. Romijn, Johannes A. Havekes, Louis M. Tamsma, Jouke T. Rensen, Patrick C. N. Hiemstra, Pieter S. Berbee, Jimmy F. P. TI Hepatocyte-specific IKK beta expression aggravates atherosclerosis development in APOE*3-Leiden mice SO ATHEROSCLEROSIS LA English DT Article DE NF-kappa B; Atherosclerosis; Mouse models; Liver; Hepatocyte; Inflammation; Lipid metabolism ID NF-KAPPA-B; LOW-GRADE INFLAMMATION; CAROTID ATHEROSCLEROSIS; TRANSGENIC MICE; DEFICIENT MICE; IMMUNE-SYSTEM; LIVER; DISEASE; MACROPHAGES; LIPOPROTEIN AB Objective: The liver is the key organ involved in systemic inflammation, but the relation between hepatic inflammation and atherogenesis is poorly understood. Since nuclear factor-kappa B (NF-kappa B) is a central regulator of inflammatory processes, we hypothesized that chronically enhanced hepatic NF-kappa B activation, through hepatocyte-specific expression of I kappa B kinase-beta (IKK beta) (LIKK), will aggravate atherosclerosis development in APOE*3-Leiden (E3L) mice. Methods and results: E3L. LIKK and E3L control littermates were fed a Western-type diet for 24 weeks. E3L. LIKK mice showed a 2.3-fold increased atherosclerotic lesion area and more advanced atherosclerosis in the aortic root with less segments without atherosclerotic lesions (11% vs. 42%), and more segments with mild (63% vs. 44%) and severe (26% vs. 14%) lesions. Expression of LIKK did not affect basal levels of inflammatory parameters, but plasma cytokine levels tended to be higher in E3L. LIKK mice after lipopolysaccharide (LPS) administration. E3L.LIKK mice showed transiently increased plasma cholesterol levels, confined to (V) LDL. This transient character resulted in a mild (+17%) increased cumulative plasma cholesterol exposure. Conclusion: We conclude that selective activation of NF-kappa B in hepatocytes considerably promotes atherosclerosis development which is (at least partly) explained by an increased sensitivity to proinflammatory triggers and transiently increased plasma cholesterol levels. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Wong, Man C.; Hiemstra, Pieter S.] Leiden Univ, Med Ctr, Dept Pulmonol, NL-2300 RC Leiden, Netherlands. [Wong, Man C.; van Diepen, Janna A.; Hu, Lihui; Voshol, Peter J.; Romijn, Johannes A.; Havekes, Louis M.; Tamsma, Jouke T.; Rensen, Patrick C. N.; Berbee, Jimmy F. P.] Leiden Univ, Med Ctr, Dept Gen Internal Med Endocrinol & Metab Dis, NL-2300 RC Leiden, Netherlands. [Guigas, Bruno] Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RC Leiden, Netherlands. [de Boer, Hetty C.; van Zonneveld, Anton J.] Leiden Univ, Med Ctr, Dept Nephrol, NL-2300 RC Leiden, Netherlands. [de Boer, Hetty C.; van Zonneveld, Anton J.] Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Med, NL-2300 RC Leiden, Netherlands. [van Puijvelde, Gijs H.; Kuiper, Johan] Gorlaeus Labs, Div Biopharmaceut, Leiden Amsterdam Ctr Drug Res, NL-2300 RA Leiden, Netherlands. [Shoelson, Steven E.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Shoelson, Steven E.] Dept Med, Boston, MA 02215 USA. [Havekes, Louis M.] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands. [Havekes, Louis M.] Gaubius Lab, Netherlands Org Appl Sci Res Biosci, NL-2301 CE Leiden, Netherlands. [Berbee, Jimmy F. P.] Sanquin Res Amsterdam, Dept Expt Immunohematol, NL-1006 AD Amsterdam, Netherlands. RP Wong, MC (reprint author), Leiden Univ, Med Ctr, Dept Pulmonol, Postzone C3-P,POB 9600, NL-2300 RC Leiden, Netherlands. EM M.C.Wong@lumc.nl RI Guigas, Bruno/M-2515-2015; van Diepen, Janna/E-9485-2010 OI Guigas, Bruno/0000-0002-8856-5799; van Diepen, Janna/0000-0001-9091-1075 FU Netherlands Organization for Scientific Research (NWO Mosaic) [017.003.83]; F.R. Nieuwenkamp stichting; Netherlands Heart Foundation [2009T038] FX This work was supported by grants from the Netherlands Organization for Scientific Research (NWO Mosaic; 017.003.83 [to L. H.]) and F.R. Nieuwenkamp stichting. P.C.N. Rensen is an Established Investigator of the Netherlands Heart Foundation (Grant 2009T038). NR 30 TC 12 Z9 12 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD FEB PY 2012 VL 220 IS 2 BP 362 EP 368 DI 10.1016/j.atherosclerosis.2011.06.055 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 879HA UT WOS:000299319100013 PM 21798539 ER PT J AU Beatty, AL Zhang, MH Ku, IA Na, B Schiller, NB Whooley, MA AF Beatty, Alexis L. Zhang, Mary H. Ku, Ivy A. Na, Beeya Schiller, Nelson B. Whooley, Mary A. TI Adiponectin is associated with increased mortality and heart failure in patients with stable ischemic heart disease: Data from the Heart and Soul Study SO ATHEROSCLEROSIS LA English DT Article DE Adiponectin; Ischemic heart disease; Outcomes; Reverse epidemiology ID CORONARY-ARTERY-DISEASE; BODY-MASS INDEX; PLASMA ADIPONECTIN; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; REVERSE EPIDEMIOLOGY; SERUM ADIPONECTIN; ELDERLY-MEN; RISK AB Objective: Serum adiponectin protects against incident ischemic heart disease (IHD). However, in patients with existing IHD, higher adiponectin levels are paradoxically associated with worse outcomes. We investigated this paradox by evaluating the relationship between adiponectin and cardiovascular events in patients with existing IHD. Methods: We measured total serum adiponectin and cardiac disease severity by stress echocardiography in 981 outpatients with stable IHD who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent heart failure hospitalizations, myocardial infarction, and death were recorded. Results: During an average of 7.1 years of follow-up, patients with adiponectin levels in the highest quartile were more likely than those in the lowest quartile to be hospitalized for heart failure (23% vs. 13%; demographics-adjusted hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.04-2.56, p = 0.03) or die (49% vs. 31%; HR 1.67, 95% CI 1.24-2.26, p < 0.008), but not more likely to have a myocardial infarction (12% vs. 17%; HR 0.64, 95% CI 0.38-1.06, p = 0.08). The combined outcome of myocardial infarction, heart failure, or death occurred in 56% (136/245) of participants in the highest quartile of adiponectin vs. 38% (94/246) of participants in the lowest quartile (HR 1.54, 95% CI 1.31-2.21, p < 0.002). Adjustment for left ventricular ejection fraction, diastolic dysfunction, inducible ischemia, C-reactive protein, and NT-proBNP attenuated the association between higher adiponectin and increased risk of subsequent events (HR 1.43, 95% CI 0.98-2.09, p = 0.06). Conclusions: Higher concentrations of adiponectin were associated with heart failure and mortality among patients with existing IHD. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Beatty, Alexis L.; Ku, Ivy A.; Schiller, Nelson B.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Zhang, Mary H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ku, Ivy A.] Kaiser Permanente, Div Cardiol, San Francisco, CA USA. [Na, Beeya; Whooley, Mary A.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Beatty, AL (reprint author), 505 Parnassus Ave,Box 0124, San Francisco, CA 94143 USA. EM alexis.beatty@ucsf.edu FU National Heart, Lung, and Blood Institute [F32HL110518]; University of California, San Francisco; Department of Veterans Affairs; National Heart, Lung and Blood Institute [R01 HL079235]; Robert Wood Johnson Foundation; American Federation for Aging Research; Ischemia Research and Education Foundation; Nancy Kirwan Heart Research Fund FX Alexis Beatty is supported by Award Number F32HL110518 from the National Heart, Lung, and Blood Institute. Mary Zhang was supported by a fellowship from the University of California, San Francisco (Medical Student Research Training Program). The Heart and Soul Study was supported by grants from the Department of Veterans Affairs (Epidemiology Merit Review Program), the National Heart, Lung and Blood Institute (R01 HL079235), the Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), the American Federation for Aging Research (Paul Bees on Faculty Scholars in Aging Research Program), the Ischemia Research and Education Foundation, and Nancy Kirwan Heart Research Fund. None of these funding sources had any role in the collection of data, interpretation of results, or preparation of this manuscript. NR 31 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD FEB PY 2012 VL 220 IS 2 BP 587 EP 592 DI 10.1016/j.atherosclerosis.2011.11.038 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 879HA UT WOS:000299319100048 PM 22196150 ER PT J AU Majhail, NS Murphy, EA Denzen, EM Ferguson, SS Anasetti, C Bracey, A Burns, L Champlin, R Hubbard, N Markowitz, M Maziarz, RT Medoff, E Neumann, J Schmit-Pokorny, K Weisdorf, DJ Raley, DSY Chell, J Snyder, EL AF Majhail, Navneet S. Murphy, Elizabeth A. Denzen, Ellen M. Ferguson, Stacy S. Anasetti, Claudio Bracey, Arthur Burns, Linda Champlin, Richard Hubbard, Norman Markowitz, Miriam Maziarz, Richard T. Medoff, Erin Neumann, Joyce Schmit-Pokorny, Kim Weisdorf, Daniel J. Raley, Deborah S. Yolin Chell, Jeffrey Snyder, Edward L. TI The National Marrow Donor Program's Symposium on Hematopoietic Cell Transplantation in 2020: A Health Care Resource and Infrastructure Assessment SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hematopoietic cell transplantation; System capacity; Workforce shortage; National Marrow Donor Program ID UNITED-STATES; PHYSICIAN; CAPACITY AB Hematopoietic cell transplantation (HCT) is the only known curative therapy for many patients with life-threatening hematologic and oncologic diseases. It is estimated that the National Marrow Donor Program (NMDP) will facilitate 10,000 transplants by 2015, double the current number. To better understand the existing personnel and center infrastructure for HCT in the country and to address system capacity challenges to the future growth of HCT, the NMDP convened a diverse group of stakeholders and thought leaders representing HCT physicians, physician assistants, nurse practitioners, nurses, pharmacists, other healthcare providers, HCT program directors, hospital administrators, payors, and professional organizations. Working groups were formed to identify: capacity issues because of shortages in human resources, structural constraints, and patient access barriers including diversity and healthcare disparity challenges; recommendations to address challenges; and stakeholders to engage. This report details the deliberations and recommendations of a national symposium, "Hematopoietic Cell Transplantation in 2020: A Health Care Resource and Infrastructure Assessment," held in September 2010. C1 [Denzen, Ellen M.] Natl Marrow Donor Program, Hlth Serv Res, Off Patient Advocacy, Minneapolis, MN 55413 USA. [Majhail, Navneet S.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Anasetti, Claudio] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Bracey, Arthur] St Lukes Episcopal Hosp, Houston, TX 77030 USA. [Burns, Linda] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Champlin, Richard; Neumann, Joyce] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hubbard, Norman] Seattle Canc Care Alliance, Seattle, WA USA. [Markowitz, Miriam] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Medoff, Erin; Snyder, Edward L.] Yale Univ, Yale New Haven Hosp, New Haven, CT USA. [Schmit-Pokorny, Kim] Univ Nebraska Med Ctr, Omaha, NE USA. [Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Raley, Deborah S. Yolin] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Denzen, EM (reprint author), Natl Marrow Donor Program, Hlth Serv Res, Off Patient Advocacy, 3001 Broadway St NE,Suite 100, Minneapolis, MN 55413 USA. EM edenzen@nmdp.org FU NCI NIH HHS [P30 CA016672] NR 17 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 BP 172 EP 182 DI 10.1016/j.bbmt.2011.10.004 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HP UT WOS:000299398500004 PM 22178961 ER PT J AU Armand, P Kim, HT Zhang, MJ Perez, WS Dal Cin, PS Klumpp, TR Waller, EK Litzow, MR Liesveld, JL Lazarus, HM Artz, AS Gupta, V Savani, BN McCarthy, PL Cahn, JY Schouten, HC Finke, J Ball, ED Aljurf, MD Cutler, CS Rowe, JM Antin, JH Isola, LM Di Bartolomeo, P Camitta, BM Alan, M Cairo, MS Stockerl-Goldstein, K Sierra, J Savoie, ML Halter, J Stiff, PJ Nabhan, C Jakubowski, AA Bunjes, DW Petersdorf, EW Devine, SM Maziarz, RI Bornhauser, M Lewis, VA Marks, DI Bredeson, CN Soiffer, RJ Weisdorf, DJ AF Armand, Philippe Kim, Haesook T. Zhang, Mei-Jie Perez, Waleska S. Dal Cin, Paola S. Klumpp, Thomas R. Waller, Edmund K. Litzow, Mark R. Liesveld, Jane L. Lazarus, Hillard M. Artz, Andrew S. Gupta, Vikas Savani, Bipin N. McCarthy, Philip L. Cahn, Jean-Yves Schouten, Harry C. Finke, Juergen Ball, Edward D. Aljurf, Mahmoud D. Cutler, Corey S. Rowe, Jacob M. Antin, Joseph H. Isola, Luis M. Di Bartolomeo, Paolo Camitta, Bruce M. Miller, Alan M. Cairo, Mitchell S. Stockerl-Goldstein, Keith Sierra, Jorge Savoie, M. Lynn Halter, Joerg Stiff, Patrick J. Nabhan, Chadi Jakubowski, Ann A. Bunjes, Donald W. Petersdorf, Effie W. Devine, Steven M. Maziarz, Richard I. Bornhauser, Martin Lewis, Victor A. Marks, David I. Bredeson, Christopher N. Soiffer, Robert J. Weisdorf, Daniel J. TI Classifying Cytogenetics in Patients with Acute Myelogenous Leukemia in Complete Remission Undergoing Allogeneic Transplantation: A Center for International Blood and Marrow Transplant Research Study SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE AML; SCT; Karyotype ID ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; RETROSPECTIVE ANALYSIS; AML-10 TRIAL; DE-NOVO; SURVIVAL; THERAPY; CLASSIFICATION; RELAPSE; IMPACT AB Cytogenetics play a major role in determining the prognosis of patients with acute myelogenous leukemia (AML). However, existing cytogenetics classifications were developed in chemotherapy-treated patients and might not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent HCT for AML in first or second complete remission between 1999 and 2004. We compared the ability of the 6 existing classifications to stratify patients by overall survival. We then defined a new scheme specifically applicable to patients undergoing HCT using this patient cohort. Under this scheme, inv(16) is favorable, a complex karyotype (4 or more abnormalities) is adverse, and all other classified abnormalities are intermediate in predicting survival after HCT (5-year overall survival, 64%, 18%, and 50%, respectively; P = .0001). This scheme stratifies patients into 3 groups with similar non-relapse mortality, but significantly different incidences of relapse, overall and leukemia-free survival. It applies to patients regardless of disease status (first or second complete remission), donor type (matched related or unrelated), or conditioning intensity (myeloablative or reduced intensity). This transplantation-specific classification could be adopted for prognostication purposes and to stratify patients with AML and karyotypic abnormalities entering HCT clinical trials. C1 [Armand, Philippe] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Zhang, Mei-Jie] Ctr Int Blood & Marrow Transplant Res, Dept Biostat, Milwaukee, WI USA. [Perez, Waleska S.] Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI USA. [Dal Cin, Paola S.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Klumpp, Thomas R.] Temple Univ, Bone Marrow Transplant Program, Bone & Marrow Transplant Program, Philadelphia, PA 19122 USA. [Waller, Edmund K.] Emory Univ Hosp, Dept Bone & Marrow Stem Cell Transplantat, Atlanta, GA 30322 USA. [Litzow, Mark R.] Mayo Clin, Dept Hematol & Internal Med, Rochester, MN USA. [Liesveld, Jane L.] Univ Rochester, Strong Mem Hosp, Med Ctr, Dept Hematol & Oncol, Rochester, NY 14642 USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Dept Med Oncol, Cleveland, OH USA. [Artz, Andrew S.] Univ Chicago Hosp, Dept Hematol & Oncol, Chicago, IL 60637 USA. [Gupta, Vikas] Princess Margaret Hosp, Dept Hematol, Toronto, ON M4X 1K9, Canada. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Hematol & Oncol, Nashville, TN USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Cahn, Jean-Yves] CHU Grenoble, Hosp A Michallon, Dept Hematol, F-38043 Grenoble, France. [Schouten, Harry C.] Acad Ziekenhuis, Dept Med, Maastricht, Netherlands. [Finke, Juergen] Univ Freiburg Klinikum, Dept Hematol & Oncol, Freiburg, Germany. [Ball, Edward D.] Univ Calif San Diego, Dept Med, Med Ctr, La Jolla, CA 92093 USA. [Aljurf, Mahmoud D.] King Faisal Specialist Hosp & Res Ctr, Dept Hematol, Riyadh 11211, Saudi Arabia. [Cutler, Corey S.] Dana Farber Canc Inst, Dept Med Oncol & Hematol Malignancies, Boston, MA 02115 USA. [Rowe, Jacob M.] Rambam Med Ctr, Dept Hematol, Haifa, Israel. [Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Isola, Luis M.] Mt Sinai Med Ctr, Dept Hematol & Oncol, New York, NY 10029 USA. [Di Bartolomeo, Paolo] Osped Civile, BMT Ctr Pescara, Dept Hematol, Pescara, Italy. [Camitta, Bruce M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Miller, Alan M.] Baylor Univ, Med Ctr, Dept Oncol, Dallas, TX USA. [Cairo, Mitchell S.] Columbia Univ, Med Ctr, Morgan Stanley Childrens Hosp New York Presbyteri, Dept Pediat Hematol & Oncol, New York, NY USA. [Stockerl-Goldstein, Keith] Washington Univ, Sch Med, Dept Bone Marrow Transplant, St Louis, MO USA. [Sierra, Jorge] Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain. [Savoie, M. Lynn] Tom Baker Canc Clin, Dept Med Oncol, Calgary, AB, Canada. [Halter, Joerg] Univ Basel Hosp, Dept Internal Med, CH-4031 Basel, Switzerland. [Stiff, Patrick J.] Loyola Univ, Med Ctr, Dept Hematol & Oncol, Maywood, IL 60153 USA. [Nabhan, Chadi] Advocate Lutheran Gen Hosp, Dept Hematol & Oncol, Park Ridge, IL USA. [Jakubowski, Ann A.] Mem Sloan Kettering Canc Ctr, Dept Hematol Oncol, New York, NY 10021 USA. [Bunjes, Donald W.] Univ Ulm Klinikum, Dept Med, Ulm, Germany. [Petersdorf, Effie W.] Fred Hutchinson Canc Res Ctr, Dept Oncol, Seattle, WA 98104 USA. [Devine, Steven M.] James Canc Ctr, Ohio State Med Ctr, Dept Blood & Marrow Transplant, Columbus, OH USA. [Maziarz, Richard I.] Oregon Hlth & Sci Univ, Dept Bone Marrow Transplant, Portland, OR 97201 USA. [Bornhauser, Martin] Univ Klinikum Carl Gustav Carus, Dept Med, Dresden, Germany. [Lewis, Victor A.] Alberta Childrens Prov Gen Hosp, Dept Hematol & Oncol, Calgary, AB T2T 5C7, Canada. [Marks, David I.] Bristol Childrens Hosp, Dept Hematol, Bristol, Avon, England. [Bredeson, Christopher N.] Froedert Mem Lutheran Hosp, Dept Med, Milwaukee, WI USA. [Soiffer, Robert J.] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Weisdorf, Daniel J.] Univ Minnesota, Dept Med, Med Ctr, Minneapolis, MN 55455 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM parmand@partners.org RI Halter, Joerg/C-9487-2012; Lopez, Dulce/A-7700-2013; Cahn, Jean-Yves/M-6493-2014 FU American Society of Hematology; American Society of Clinical Oncology; National Institute of Allergy and Infectious Diseases (NIAID) [U19 AI 29530]; National Heart, Lung and Blood Institute (NHLBI) [PO1 HL 070149]; Public Health Service from the National Cancer Institute [U24-CA76518]; NHLBI [5U01HL069294]; NIAID; National Cancer Institute; Health Resources and Services Administration [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos; Amgen; Angioblast FX Philippe Armand is supported by an American Society of Hematology Scholar Award and an American Society of Clinical Oncology Career Development Award. This work was also supported by National Institute of Allergy and Infectious Diseases (NIAID) Grant U19 AI 29530 and National Heart, Lung and Blood Institute (NHLBI) Grant PO1 HL 070149. The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute, NHLBI, and NIAID; Grant/Cooperative Agreement 5U01HL069294 from the NHLBI and National Cancer Institute; Contract HHSH234200637015C with the Health Resources and Services Administration; Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Amgen, Angioblast, anonymous donation to the Medical College of Wisconsin, Ariad, Be the Match Foundation, Blue Cross and Blue Shield Association, Buchanan Family Foundation, CaridianBCT, Celgene, CellGenix, Children's Leukemia Research Association, Fresenius-Biotech North America, Gamida Cell Teva Joint Venture, Genentech, Genzyme, GlaxoSmithKline, Kiadis Pharma, Leukemia and Lymphoma Society, Medical College of Wisconsin, Millennium Pharmaceuticals, Milliman USA, Miltenyi Biotec, National Marrow Donor Program, Optum Healthcare Solutions, Otsuka America Pharmaceutical, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, Swedish Orphan Biovitrum, THERAKOS, and Wellpoint. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government. NR 21 TC 33 Z9 34 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 BP 280 EP 288 DI 10.1016/j.bbmt.2011.07.024 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HP UT WOS:000299398500017 PM 21810400 ER PT J AU Lu, YH Zhang, GL Shen, C Uygun, K Yarmush, ML Meng, Q AF Lu, Yanhua Zhang, Guoliang Shen, Chong Uygun, Korkut Yarmush, Martin L. Meng, Qin TI A novel 3D liver organoid system for elucidation of hepatic glucose metabolism SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE rat hepatocytes; 3D organoid culture; hollow fiber bioreactor; glucose metabolism ID DRUG-INDUCED HEPATOTOXICITY; CULTURED RAT HEPATOCYTES; GENE-EXPRESSION; GLYCOGEN-METABOLISM; OXIDATIVE STRESS; HOLLOW FIBERS; CELL-LINES; LONG-TERM; DEXAMETHASONE; INSULIN AB Hepatic glucose metabolism is a key player in diseases such as obesity and diabetes as well as in antihyperglycemic drugs screening. Hepatocytes culture in two-dimensional configurations is limited in vitro model for hepatocytes to function properly, while truly practical platforms to perform three-dimensional (3D) culture are unavailable. In this work, we present a practical organoid culture method of hepatocytes for elucidation of glucose metabolism under nominal and stress conditions. Employing this new method of culturing cells within a hollow fiber reactor, hepatocytes were observed to self-assemble into 3D spherical organoids with preservation of tight junctions and display increased liver-specific functions. Compared to both monolayer culture and sandwich culture, the hepatocyte organoids displayed higher intracellular glycogen content, glucose consumption, and gluconeogenesis and approached the in vivo values, as also confirmed by gene expression of key enzymes. Moreover, hepatocyte organoids demonstrated more realistic sensitivity to hormonal challenges with insulin, glucagon, and dexamethasone. Finally, the exposure to high glucose demonstrated toxicities including alteration of mitochondrial membrane potential, lipid accumulation, and reactive oxygen species formation, similar to the in vivo responses, which was not captured by monolayer cultures. Collectively, hepatocyte organoids mimicked the in vivo functions better than hepatocyte monolayer and sandwich cultures, suggesting suitability for applications such as antihyperglycemic drugs screening. Biotechnol. Bioeng. 2012; 109:595604. (c) 2011 Wiley Periodicals, Inc. C1 [Lu, Yanhua; Shen, Chong; Meng, Qin] Zhejiang Univ, Dept Chem & Biol Engn, Hangzhou 310027, Zhejiang, Peoples R China. [Zhang, Guoliang] Zhejiang Univ Technol, Inst Biol & Environm Engn, Hangzhou 310012, Zhejiang, Peoples R China. [Uygun, Korkut; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA USA. [Uygun, Korkut; Yarmush, Martin L.] Shriners Burns Hosp, Boston, MA USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Meng, Q (reprint author), Zhejiang Univ, Dept Chem & Biol Engn, 38 Zheda Rd, Hangzhou 310027, Zhejiang, Peoples R China. EM mengq@zju.edu.cn FU NSFC (National Natural Science Foundation of China) [20576119, 30772614]; National Institutes of Health [R01DK59766, R00DK080942] FX This research was supported by grants (No. 20576119 and 30772614) from NSFC (National Natural Science Foundation of China). K.U. and M.Y were supported partially by National Institutes of Health (R01DK59766 and R00DK080942). NR 50 TC 11 Z9 11 U1 4 U2 21 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD FEB PY 2012 VL 109 IS 2 BP 595 EP 604 DI 10.1002/bit.23349 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 861LP UT WOS:000298020700030 PM 22006574 ER PT J AU Singh, H Giardina, TD Forjuoh, SN Reis, MD Kosmach, S Khan, MM Thomas, EJ AF Singh, Hardeep Giardina, Traber Davis Forjuoh, Samuel N. Reis, Michael D. Kosmach, Steven Khan, Myrna M. Thomas, Eric J. TI Electronic health record-based surveillance of diagnostic errors in primary care SO BMJ QUALITY & SAFETY LA English DT Article ID ADVERSE DRUG EVENTS; MALPRACTICE CLAIMS; CANCER-DIAGNOSIS; PATIENT SAFETY; MISSED OPPORTUNITIES; GENERAL-PRACTICE; MEDICAL-RECORD; UNITED-STATES; CLASSIFICATION; STRATEGIES AB Background: Diagnostic errors in primary care are harmful but difficult to detect. The authors tested an electronic health record (EHR)-based method to detect diagnostic errors in routine primary care practice. Methods: The authors conducted a retrospective study of primary care visit records 'triggered' through electronic queries for possible evidence of diagnostic errors: Trigger 1: A primary care index visit followed by unplanned hospitalisation within 14 days and Trigger 2: A primary care index visit followed by >= 1 unscheduled visit(s) within 14 days. Control visits met neither criterion. Electronic trigger queries were applied to EHR repositories at two large healthcare systems between 1 October 2006 and 30 September 2007. Blinded physician-reviewers independently determined presence or absence of diagnostic errors in selected triggered and control visits. An error was defined as a missed opportunity to make or pursue the correct diagnosis when adequate data were available at the index visit. Disagreements were resolved by an independent third reviewer. Results: Queries were applied to 212 165 visits. On record review, the authors found diagnostic errors in 141 of 674 Trigger 1-positive records (positive predictive value (PPV)=20.9%, 95% CI 17.9% to 24.0%) and 36 of 669 Trigger 2-positive records (PPV=5.4%, 95% CI 3.7% to 7.1%). The control PPV of 2.1% (95% CI 0.1% to 3.3%) was significantly lower than that of both triggers (p <= 0.002). Inter-reviewer reliability was modest, though higher than in comparable previous studies (K=0.37 (95% CI 0.31 to 0.44)). Conclusions: While physician agreement on diagnostic error remains low, an EHR-facilitated surveillance methodology could be useful for gaining insight into the origin of these errors. C1 [Singh, Hardeep; Giardina, Traber Davis; Khan, Myrna M.] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Singh, Hardeep; Giardina, Traber Davis; Khan, Myrna M.] Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. [Forjuoh, Samuel N.; Reis, Michael D.] Texas A&M Hlth Sci Ctr, Coll Med, Dept Family & Community Med, Scott & White Healthcare, Temple, TX USA. [Kosmach, Steven] Univ Texas Hlth Sci Ctr Houston, Div Biostat, Sch Publ Hlth, Houston, TX USA. [Thomas, Eric J.] Univ Texas Houston, Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. [Thomas, Eric J.] Univ Texas Med Sch Houston, Div Gen Med, Dept Med, Houston, TX USA. RP Singh, H (reprint author), Baylor Coll Med, VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu OI Davis Giardina, Traber/0000-0002-9184-6524 FU NIH [K23CA125585]; Agency for Health Care Research and Quality Health Services [R18HS17244-02]; Houston VA HSR&D Center of Excellence [HFP90-020] FX The study was supported by an NIH K23 career development award (K23CA125585) to HS, Agency for Health Care Research and Quality Health Services Research Demonstration and Dissemination Grant (R18HS17244-02) to EJT and in part by the Houston VA HSR&D Center of Excellence (HFP90-020). These sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. NR 48 TC 28 Z9 28 U1 3 U2 13 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD FEB PY 2012 VL 21 IS 2 BP 93 EP 100 DI 10.1136/bmjqs-2011-000304 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 879JF UT WOS:000299324800002 PM 21997348 ER PT J AU Higgins, MJ Prowell, TM Blackford, AL Byrne, C Khouri, NF Slater, SA Jeter, SC Armstrong, DK Davidson, NE Emens, LA Fetting, JH Powers, PP Wolff, AC Green, H Thibert, JN Rae, JM Folkerd, E Dowsett, M Blumenthal, RS Garber, JE Stearns, V AF Higgins, Michaela J. Prowell, Tatiana M. Blackford, Amanda L. Byrne, Celia Khouri, Nagi F. Slater, Shannon A. Jeter, Stacie C. Armstrong, Deborah K. Davidson, Nancy E. Emens, Leisha A. Fetting, John H. Powers, Pendleton P. Wolff, Antonio C. Green, Hannah Thibert, Jacklyn N. Rae, James M. Folkerd, Elizabeth Dowsett, Mitchell Blumenthal, Roger S. Garber, Judy E. Stearns, Vered TI A short-term biomarker modulation study of simvastatin in women at increased risk of a new breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Simvastastin; Breast density; Chemoprevention; Breast cancer; Contralateral breast ID SURGICAL ADJUVANT BREAST; C-REACTIVE PROTEIN; STAR P-2 TRIAL; POSTMENOPAUSAL WOMEN; MAMMOGRAPHIC DENSITY; AROMATASE INHIBITOR; ESTRONE SULFATE; DEHYDROEPIANDROSTERONE-SULFATE; HORMONE-LEVELS; BOWEL PROJECT AB Observational studies have demonstrated a decreased incidence of cancers among users of HMG CoA reductase inhibitors (statins) and a reduced risk of recurrence among statin users diagnosed with early stage breast cancer. We initiated a prospective study to identify potential biomarkers of simvastatin chemopreventive activity that can be validated in future trials. The contralateral breast of women with a previous history of breast cancer was used as a high-risk model. Eligible women who had completed all planned treatment of a prior stage 0-III breast cancer received simvastatin 40 mg orally daily for 24-28 weeks. At baseline and end-of-study, we measured circulating concentrations of high-sensitivity C-reactive protein (hsCRP), estrogens, and fasting lipids; breast density on contralateral breast mammogram; and quality of life by Rand Short Form 36-Item health survey. Fifty women were enrolled with a median age of 53 years. Total cholesterol, LDL cholesterol, triglyceride, and hsCRP fell significantly during the study (P values < 0.001, < 0.001, 0.003, and 0.05, respectively). Estrone sulfate concentrations decreased with simvastatin treatment (P = 0.01 overall), particularly among post-menopausal participants (P = 0.006). We did not observe a significant change in circulating estradiol or estrone concentrations, contralateral mammographic breast density, or reported physical functioning or pain scores. This study demonstrates the feasibility of short-term biomarker modulation studies using the contralateral breast of high-risk women. Simvastatin appears to modulate estrone sulfate concentrations and its potential chemopreventive activity in breast cancer warrants further investigation. C1 [Higgins, Michaela J.; Prowell, Tatiana M.; Blackford, Amanda L.; Khouri, Nagi F.; Slater, Shannon A.; Jeter, Stacie C.; Armstrong, Deborah K.; Davidson, Nancy E.; Emens, Leisha A.; Fetting, John H.; Powers, Pendleton P.; Wolff, Antonio C.; Blumenthal, Roger S.; Stearns, Vered] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, CRBI, Baltimore, MD 21231 USA. [Byrne, Celia] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Green, Hannah; Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Thibert, Jacklyn N.; Rae, James M.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Folkerd, Elizabeth; Dowsett, Mitchell] Royal Marsden Hosp, Acad Dept Biochem, London SW3 6JJ, England. RP Stearns, V (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, CRBI, 1650 Orleans St,Room 144, Baltimore, MD 21231 USA. EM vstearn1@jhmi.edu RI Byrne, Christopher/D-2824-2016; Byrne, Celia/K-2964-2015; OI Byrne, Celia/0000-0001-8289-4252; Wolff, Antonio/0000-0003-3734-1063 FU National Cancer Institutes-AVON Progress for Patients [P50CA88843-AV82P P50CA89393]; Breast Cancer Research Foundation; Merck; Novartis; Pfizer Inc; Genentech, Inc.; Roche, Inc. FX The study was supported by National Cancer Institutes-AVON Progress for Patients (P50CA88843-AV82P P50CA89393 to VS and JG), the Breast Cancer Research Foundation (VS and JMR). Six month supply of simvastatin was provided by Merck & Co. Ltd. The 36-Item Health Survey was developed at RAND as part of the Medical Outcomes Study.; Dr. Stearns is the recipient of investigator-initiated grants from Merck, Novartis and Pfizer Inc and has received honoraria from AstraZeneca. Dr. Emens received funding from Genentech, Inc. and Roche, Inc., and is a consultant to Genentech, Inc. Prof. Dowsett received honoraria, funding, and is an advisor to AstraZeneca. All of the other authors declare that they have no conflict of interest. NR 51 TC 24 Z9 25 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2012 VL 131 IS 3 BP 915 EP 924 DI 10.1007/s10549-011-1858-7 PG 10 WC Oncology SC Oncology GA 879QE UT WOS:000299346100019 PM 22076478 ER PT J AU Collins, LC Marotti, JD Gelber, S Cole, K Ruddy, K Kereakoglow, S Brachtel, EF Schapira, L Come, SE Winer, EP Partridge, AH AF Collins, L. C. Marotti, J. D. Gelber, S. Cole, K. Ruddy, K. Kereakoglow, S. Brachtel, E. F. Schapira, L. Come, S. E. Winer, E. P. Partridge, A. H. TI Pathologic features and molecular phenotype by patient age in a large cohort of young women with breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Molecular phenotypes; Young women; Prognosis; Luminal ID GENE-EXPRESSION PATTERNS; BASAL-LIKE SUBTYPE; TUMOR SUBTYPES; SURVIVAL; CARCINOMA; PROGNOSIS; DIAGNOSIS; DISEASE; RACE AB Prior studies have suggested a higher prevalence of high grade, ER-negative, HER2-positive, and basal-like carcinomas in young women with breast cancer. However, the precise distribution of poor prognostic features in this population remains unclear. We examined the pathologic features and distribution of molecular phenotype in relation to patient age in a large group of young women (a parts per thousand currency sign40 years) with invasive breast cancer. Medical records were reviewed for clinical characteristics, tumor stage, and receptor status. Pathologic features, including those features associated with basal-like carcinomas, were examined by central review. Using tumor grade and biomarker expression, cancers were categorized as luminal A (ER+ and/or PR+ and HER2-, histologic grade 1 or 2); luminal B (ER+ and/or PR+ and HER2+, or ER and/or PR+, HER2- and grade 3); HER2 (ER and PR- and HER2+); and triple negative (ER-, PR-, and HER2-). Among 399 women of a parts per thousand currency sign40 years, 33% had luminal A tumors, 35% luminal B, 11% HER2 (ER-negative), and 21% triple negative. Compared to published results for all breast cancers, a greater proportion of young women had luminal B tumors, and a lesser proportion had luminal A. There were no significant differences in molecular phenotype, tumor stage or grade among the different age groups of young women. However, this population of young women presented with a different distribution of molecular phenotypes compared to the general population of women with breast cancer. These findings may have implications with regard to the etiology and prognosis of breast cancer in young women. C1 [Collins, L. C.; Come, S. E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Collins, L. C.; Ruddy, K.; Brachtel, E. F.; Schapira, L.; Come, S. E.; Winer, E. P.; Partridge, A. H.] Harvard Univ, Sch Med, Boston, MA USA. [Marotti, J. D.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Marotti, J. D.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Gelber, S.; Ruddy, K.; Kereakoglow, S.; Winer, E. P.; Partridge, A. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cole, K.] Metrow Med Ctr, Framingham, MA USA. [Brachtel, E. F.; Schapira, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Collins, LC (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM lcollins@bidmc.harvard.edu RI Yu, Keith/K-8488-2013 NR 35 TC 71 Z9 75 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2012 VL 131 IS 3 BP 1061 EP 1066 DI 10.1007/s10549-011-1872-9 PG 6 WC Oncology SC Oncology GA 879QE UT WOS:000299346100035 PM 22080245 ER PT J AU Pichon, S de Gelder, B Grezes, J AF Pichon, Swann de Gelder, Beatrice Grezes, Julie TI Threat Prompts Defensive Brain Responses Independently of Attentional Control SO CEREBRAL CORTEX LA English DT Article DE attention; defense; emotion; fMRI; threat ID DYNAMIC BODY EXPRESSIONS; PREFRONTAL CORTICAL PROJECTIONS; MIDBRAIN PERIAQUEDUCTAL GRAY; FEAR-POTENTIATED STARTLE; MEDIAL FRONTAL-CORTEX; MOTOR AREAS; EMOTIONAL EXPRESSION; FACIAL EXPRESSIONS; CEREBRAL-CORTEX; FUNCTIONAL SPECIALIZATION AB Negative emotional signals are known to influence task performance, but so far, investigations have focused on how emotion interacts with perceptual processes by mobilizing attentional resources. The attention-independent effects of negative emotional signals are less well understood. Here, we show that threat signals trigger defensive responses independently of what observers pay attention to. Participants were scanned using functional magnetic resonance imaging while watching short video clips of threatening actions and performed either color or emotion judgments. Seeing threatening actions interfered with performance in both tasks. Amygdala activation reflected both stimulus and task conditions. In contrast, threat stimuli prompted a constant activity in a network underlying reflexive defensive behavior (periaqueductal gray, hypothalamus, and premotor cortex). Threat stimuli also disrupted ongoing behavior and provoked motor conflict in prefrontal regions during both tasks. The present results are consistent with the view that emotions trigger adaptive action tendencies independently of task settings. C1 [Pichon, Swann; Grezes, Julie] Ecole Normale Super, Cognit Neurosci Lab, Dept Cognit Studies, INSERM,U960, F-75005 Paris, France. [Pichon, Swann] Univ Geneva, Lab Behav Neurol & Imaging Cognit, Dept Neurosci, Sch Med, CH-1211 Geneva, Switzerland. [de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. [de Gelder, Beatrice] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Grezes, J (reprint author), Ecole Normale Super, Cognit Neurosci Lab, Dept Cognit Studies, INSERM,U960, F-75005 Paris, France. EM julie.grezes@ens.fr RI pichon, swann/M-2966-2014; Grezes, Julie/E-5060-2016 OI pichon, swann/0000-0001-5697-702X; FU Human Frontier Science program [HFSP-RGP0054/2004-C]; European Union [FP6-2005-NEST-Path Imp 043403]; Bettencourt Schueller Foundation FX Human Frontier Science program (HFSP-RGP0054/2004-C) and the European Union research funding NEST program (FP6-2005-NEST-Path Imp 043403). The Cognitive Neuroscience Laboratory is supported by the Bettencourt Schueller Foundation. NR 120 TC 48 Z9 48 U1 9 U2 30 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD FEB PY 2012 VL 22 IS 2 BP 274 EP 285 DI 10.1093/cercor/bhr060 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 876RD UT WOS:000299124400004 PM 21666127 ER PT J AU Takahashi, E Folkerth, RD Galaburda, AM Grant, PE AF Takahashi, Emi Folkerth, Rebecca D. Galaburda, Albert M. Grant, Patricia E. TI Emerging Cerebral Connectivity in the Human Fetal Brain: An MR Tractography Study SO CEREBRAL CORTEX LA English DT Article DE brain; development; diffusion imaging; human fetus; tractography ID WHITE-MATTER; NEURONAL MIGRATION; DIFFUSION TENSOR; CORTEX; PATHWAYS; SYSTEM; SCHIZOPHRENIA; MONKEY; DIFFERENTIATION; POLYMICROGYRIA AB Cerebral axonal connections begin to develop before birth during radial migration in each brain area. A number of theories are still actively debated regarding the link between neuronal migration, developing connectivity, and gyrification. Here, we used high angular resolution diffusion tractography on postmortem fetal human brains (postconception week (W) 17-40) to document the regression of radial and tangential organization likely to represent migration pathways and the emergence of corticocortical organization and gyrification. The dominant radial organization at W17 gradually diminished first in dorsal parieto-occipital and later in ventral frontotemporal regions with regional variation: radial organization persisted longer in the crests of gyri than at the depths of sulci. The dominant tangential organization of the ganglionic eminence at W17 also gradually disappeared by term, together with the disappearance of the ganglionic eminence. A few immature long-range association pathways were visible at W17, gradually became evident by term. Short-range corticocortical tracts emerged prior to gyrification in regions where sulci later developed. Our results suggest that the regional regression of radial organization and regional emergence of fetal brain connectivity proceeds in general from posterodorsal to anteroventral with local variations. C1 [Takahashi, Emi; Grant, Patricia E.] Harvard Univ, Sch Med, Dept Med, Div Newborn Med,Childrens Hosp Boston, Boston, MA 02115 USA. [Takahashi, Emi; Grant, Patricia E.] Harvard Univ, Sch Med, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Childrens Hosp Boston, Boston, MA 02115 USA. [Takahashi, Emi; Grant, Patricia E.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02119 USA. [Folkerth, Rebecca D.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Folkerth, Rebecca D.] Harvard Univ, Sch Med, Dept Pathol, Childrens Hosp Boston, Boston, MA 02115 USA. [Galaburda, Albert M.] Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Grant, Patricia E.] Harvard Univ, Sch Med, Dept Radiol, Childrens Hosp Boston, Boston, MA 02115 USA. RP Takahashi, E (reprint author), Harvard Univ, Sch Med, Dept Med, Div Newborn Med,Childrens Hosp Boston, Boston, MA 02115 USA. EM emi@nmr.mgh.harvard.edu FU Ellison Medical Foundation [208556]; NICHD [PO1 HD057853]; Children's Hospital Boston FX Ellison Medical Foundation (#208556); NICHD grant (PO1 HD057853) to A.M.G; and Children's Hospital Boston. NR 71 TC 62 Z9 62 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD FEB PY 2012 VL 22 IS 2 BP 455 EP 464 DI 10.1093/cercor/bhr126 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 876RD UT WOS:000299124400020 PM 21670100 ER PT J AU Huddleston, JI Wang, Y Uquillas, C Herndon, JH Maloney, WJ AF Huddleston, James I. Wang, Yun Uquillas, Carlos Herndon, James H. Maloney, William J. TI Age and Obesity Are Risk Factors for Adverse Events After Total Hip Arthroplasty SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Scientific Meeting of the Hip-Society/Annual Meeting of the American-Academy-of-Orthopaedic-Surgeons CY 2011 CL San Diego, CA SP Hip Soc, Amer Acad Orthopaed Surg ID UNITED-STATES; KNEE; OSTEOARTHRITIS; MORTALITY; OUTCOMES AB Defining the epidemiology of adverse events after THA will aid in the development of strategies to enhance perioperative care. We identified (1) risk factors for adverse events in Medicare beneficiaries while hospitalized after THA and (2) trends in the rates of adverse events. Data were abstracted from medical records of 1809 Medicare beneficiaries who underwent THA from 2002 to 2007. We used the hierarchical generalized linear modeling approach to assess the odds of change in adverse events over time, the association of adverse events with outcomes, and the relationship of adverse events with patient characteristics by modeling the log-odds of adverse events as a function of demographic and clinical variables adjusted for year variable. The overall rate of adverse events was 5.8%; the 30-day mortality rate was 1.00%. Increased age, obesity, and year of procedure were risk factors for experiencing any adverse event. Annual rates of adverse events from 2002 to 2007 were 9.1%, 8.2%, 4.9%, 4.1%, 3.5%, and 3.0%, respectively. Experiencing any adverse event was associated with an increased length of stay and an increased chance of readmission but not with an increased chance of mortality. The annual rate of all adverse events decreased from 2002-2004 to 2005-2007 (odds ratio = 0.83; 95% confidence interval, 0.74-0.92). Older and obese patients should be counseled regarding their increased risk for the development of adverse events after THA. The cause of the decline in the rate of adverse events between two time periods is unclear and warrants further investigation to confirm and identify the cause. C1 [Huddleston, James I.; Uquillas, Carlos; Maloney, William J.] Stanford Med Outpatient Ctr, Dept Orthopaed Surg, Redwood City, CA 94063 USA. [Wang, Yun] Qualidigm Inc, Middletown, CT USA. [Wang, Yun] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Herndon, James H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Huddleston, JI (reprint author), Stanford Med Outpatient Ctr, Dept Orthopaed Surg, 450 Broadway St,Mailcode 6324, Redwood City, CA 94063 USA. EM jhuddleston@stanford.edu NR 14 TC 41 Z9 42 U1 0 U2 4 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 FEB PY 2012 VL 470 IS 2 BP 490 EP 496 DI 10.1007/s11999-011-1967-y PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 875SU UT WOS:000299056000022 PM 21796477 ER PT J AU Silva, GS Schwamm, LH AF Silva, Gisele Sampaio Schwamm, Lee H. TI Use of Telemedicine and Other Strategies to Increase the Number of Patients That May Be Treated with Intravenous Thrombolysis SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Telemedicine; Telestroke; Acute stroke care; Intravenous thrombolysis ID ACUTE ISCHEMIC-STROKE; PLASMINOGEN-ACTIVATOR; ALTEPLASE TREATMENT; TELESTROKE; CARE; ASSOCIATION; MANAGEMENT; BARRIERS; TRIALS; IMPLEMENTATION AB Stroke is the fourth leading killer in the United States and a leading cause of adult long-term disability. The American Heart Association estimates that only 3% to 5% of patients with acute ischemic stroke are treated with intravenous thrombolysis. A way to improve the rates of treatment with thrombolysis in patients with acute ischemic stroke is the creation of telemedicine stroke networks. Data from many studies support the safety of expanding intravenous tissue plasminogen activator use with the help of telemedicine. In this article we discuss the current evidence for the use of telemedicine within stroke systems of care, the importance of coordinating care within the transferring facilities in the telestroke networks, telestroke economics and applicability, and how to potentially use the telestroke systems to increase recruitment of patients into acute stroke thrombolysis trials. C1 [Silva, Gisele Sampaio] Univ Fed Sao Paulo, Dept Neurol & Neurosurg, Sao Paulo, Brazil. [Silva, Gisele Sampaio] Albert Einstein Hosp, Albert Einstein Neurol Program, Sao Paulo, Brazil. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, TeleStroke Serv, Boston, MA 02114 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Acute Stroke Serv, Boston, MA 02114 USA. [Schwamm, Lee H.] Harvard Univ, Sch Med, Boston, MA USA. RP Silva, GS (reprint author), Dr Altino Arantes Ave 741,81, BR-04042033 Sao Paulo, Brazil. EM giselesampaio@hotmail.com; lschwamm@partners.org OI Schwamm, Lee/0000-0003-0592-9145 NR 45 TC 12 Z9 12 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD FEB PY 2012 VL 12 IS 1 BP 10 EP 16 DI 10.1007/s11910-011-0235-6 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 875TA UT WOS:000299056600002 PM 21997715 ER PT J AU Kerlikowske, K AF Kerlikowske, Karla TI Screening mammography in women less than age 50 years SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Review DE benefits and harms; digital mammography; risk-based screening; screening mammography ID CARCINOMA IN-SITU; SERVICES TASK-FORCE; BREAST-CANCER RISK; FALSE-POSITIVE MAMMOGRAMS; COST-EFFECTIVENESS; SURVEILLANCE CONSORTIUM; ABNORMAL MAMMOGRAMS; AMERICAN-COLLEGE; FILM MAMMOGRAPHY; UNITED-STATES AB Purpose of review For women aged 40-49 years, to describe the benefits and harms of performing screening mammography, accuracy of digital mammography, and new evidence on the effectiveness of risk-based screening. Recent findings New data support a 15% reduction in breast cancer mortality for women aged 40-49 years after 10 years of screening; however, the absolute benefit is small and not outweighed by important harms. Digital mammography is more sensitive, but less specific than film mammography in women aged 40-49 years. Risk-based screening that identifies and screens women aged 40-49 years with breast cancer risk similar to an average-risk woman aged 50-59 years results in similar benefits and harms of screening these high-risk women as screening average-risk 50-year-old women. Summary Practitioners should discuss with women aged 40-49 years the benefits and harms of undergoing screening mammography before offering them screening. If women elect to undergo screening mammography, they should undergo biennial screening with digital mammography. Targeting screening for those women aged 40-49 years with risk factors that substantially increase the risk of breast cancer, such as high breast density, family history of breast cancer, and history of benign breast biopsy, could maximize the benefits and minimizes the harms of screening this age group. C1 [Kerlikowske, Karla] Univ Calif San Francisco, Gen Internal Med Sect, Dept Vet Affairs, San Francisco, CA 94143 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Kerlikowske, K (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM Karla.Kerlikowske@ucsf.edu NR 46 TC 6 Z9 6 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-872X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD FEB PY 2012 VL 24 IS 1 BP 38 EP 43 DI 10.1097/GCO.0b013e32834da49a PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 876PD UT WOS:000299118800007 PM 22037165 ER PT J AU Egede, LE Dismuke, CE AF Egede, Leonard E. Dismuke, Clara E. TI Serious Psychological Distress and Diabetes: A Review of the Literature SO CURRENT PSYCHIATRY REPORTS LA English DT Review DE Kessler; Psychological distress; Serious psychological distress; Diabetes; Depression; Schizophrenia; Post-traumatic stress disorder; PTSD; Diabetes distress; Anxiety ID CORONARY-HEART-DISEASE; MAJOR DEPRESSION; GLYCEMIC CONTROL; MEDICATION ADHERENCE; COMORBID DEPRESSION; GENERAL-POPULATION; PROSPECTIVE COHORT; MENTAL-ILLNESS; HEALTH-CARE; LOW-INCOME AB With the development of a measure of serious psychological distress (SPD) in 2002, more attention is being paid to the association of SPD with diabetes outcomes and processes of care. We review the literature on the relationship between SPD and diabetes processes of care and outcomes, as well as the literature on the relationship between specific mental health diagnoses and diabetes processes of care and outcomes during the 2010 to 2011 period. There is an extensive literature on the association of mental health diagnoses with diabetes outcomes, especially for depression. Because the Kessler scale measures a much broader range of mental health issues than any specific DSM-IV/Structured Clinical Interview for DSM Disorders diagnosis and is designed to assess SPD at the population level, additional research needs to be conducted both in clinical settings and using large administrative datasets to examine the association between SPD and diabetes outcomes and processes of care. C1 [Egede, Leonard E.; Dismuke, Clara E.] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29425 USA. [Egede, Leonard E.; Dismuke, Clara E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU Center for Disease Prevention and Health Interventions for Diverse Populations HSRD [REA 08-261] FX The authors acknowledge and appreciate the resources provided by the Center for Disease Prevention and Health Interventions for Diverse Populations HSR&D program (grant REA 08-261) and the Ralph H. Johnson Veterans Affairs Medical Center. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 65 TC 35 Z9 35 U1 11 U2 31 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD FEB PY 2012 VL 14 IS 1 BP 15 EP 22 DI 10.1007/s11920-011-0240-0 PG 8 WC Psychiatry SC Psychiatry GA 876FJ UT WOS:000299092700003 PM 22002804 ER PT J AU Hazlett, EA Goldstein, KE Kolaitis, JC AF Hazlett, Erin A. Goldstein, Kim E. Kolaitis, Jeanine C. TI A Review of Structural MRI and Diffusion Tensor Imaging in Schizotypal Personality Disorder SO CURRENT PSYCHIATRY REPORTS LA English DT Review DE Schizotypal personality disorder; Schizotypy; MRI; Diffusion tensor; Diffusion tensor imaging; Fractional anisotropy; DTI; White matter; Gray matter; Morphometry; Schizophrenia; Schizophrenia spectrum; Brain volume; Frontal lobe; Temporal lobe; Superior temporal gyrus; Cingulate; Cingulum ID SUPERIOR TEMPORAL GYRUS; WHITE-MATTER INTEGRITY; LOBE GRAY-MATTER; ANTERIOR CINGULATE; SCHIZOPHRENIA SPECTRUM; INTERNAL CAPSULE; ONSET SCHIZOPHRENIA; UNCINATE FASCICULUS; HUMAN BRAIN; VOLUME AB Individuals with schizotypal personality disorder (SPD) share genetic, phenomenologic, and cognitive abnormalities with people diagnosed with schizophrenia. To date, 15 structural MRI studies of the brain have examined size, and 3 diffusion tensor imaging studies have examined white matter connectivity in SPD. Overall, both types of structural neuroimaging modalities have shown temporal lobe abnormalities similar to those observed in schizophrenia, while frontal lobe regions appear to show more sparing. This intriguing pattern suggests that frontal lobe sparing may suppress psychosis, which is consistent with the idea of a possible neuroprotective factor. In this paper, we review these 18 studies and discuss whether individuals with SPD who both resemble and differ from schizophrenia patients in their phenomenology, share some or all of the structural brain imaging characteristics of schizophrenia. We attempt to group the MRI abnormalities in SPD into three patterns: 1) a spectrum of severity-abnormalities are similar to those observed in schizophrenia but not so severe; 2) a spectrum of region-abnormalities affecting some, but not all, brain regions affected in schizophrenia; and 3) a spectrum of compensation-abnormalities reflecting greater-than-normal white matter volume, possibly serving as a buffer or compensatory mechanism protecting the individual with SPD from the frank psychosis observed in schizophrenia. C1 [Hazlett, Erin A.; Kolaitis, Jeanine C.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN3, Bronx, NY 10468 USA. [Hazlett, Erin A.; Kolaitis, Jeanine C.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Goldstein, Kim E.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. RP Hazlett, EA (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN3, 130 W Kingsbridge Rd,Room 6A-45, Bronx, NY 10468 USA. EM erin.hazlett@mssm.edu FU VA MERIT [I01 CX000261] FX Support for this work came from VA MERIT I01 CX000261 (to Dr. Hazlett). NR 70 TC 25 Z9 26 U1 2 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD FEB PY 2012 VL 14 IS 1 BP 70 EP 78 DI 10.1007/s11920-011-0241-z PG 9 WC Psychiatry SC Psychiatry GA 876FJ UT WOS:000299092700010 PM 22006127 ER PT J AU Brisman, JL Pile-Spellman, J Konstas, AA AF Brisman, Jonathan L. Pile-Spellman, John Konstas, Angelos A. TI Clinical utility of quantitative magnetic resonance angiography in the assessment of the underlying pathophysiology in a variety of cerebrovascular disorders SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Quantitative MRA; Phase-contrast; Parvus-tardus; Volumetric flow rates ID CEREBRAL-BLOOD-FLOW; ARTERY-STENOSIS; DISEASE; MALFORMATIONS AB Background: Quantitative MRA (qMRA) is a relatively new technique that uses traditional time-of-flight and phase-contrast MRI to visualize extracranial and intracranial vascular anatomy and measure volumetric blood flow. We aimed to assess the clinical utility of qMRA in assessing the hypothesized pathophysiology (HP) in a range of cerebrovascular diseases. Moreover, we postulated that evaluation of the arterial waveforms, can improve the evaluation of the hypothesized pathophysiology by qMRA. Methods: We reviewed studies from 10 patients who underwent qMRA examinations before and after their treatments. Two reviewers assessed the anatomy, volumetric flow rates and arterial waveforms for each vessel sampled and reached a consensus as to whether the above parameters supported the clinical diagnosis/hypothesized pathophysiology and the subsequent management. Findings: All 20 qMRA studies were technically adequate. qMRA supported the HP in all 10 patients as determined by abnormal volumetric flow values in the affected vessels before treatment and by the correction of these abnormal values in the patients whose treatment was successful. Each of our five patients with occlusive disease/vasoconstriction demonstrated evidence of dampening of the arterial waveforms distally to the narrowed artery (parvus-tardus phenomenon). The parvus-tardus effect disappeared after treatment. Conclusion: qMRA is unique in combining time-of-flight MRA in a complementary manner with phase-contrast MRA to obtain volumetric flow values and potentially important physiologic information from arterial waveform analysis in patients with a range of cerebrovascular diseases during the course of a single MR examination. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Brisman, Jonathan L.; Pile-Spellman, John] Wintrop Univ Hosp, Lake Success, NY 11042 USA. [Konstas, Angelos A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Konstas, Angelos A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Brisman, JL (reprint author), Wintrop Univ Hosp, 1991 Marcus Ave,Suite 108, Lake Success, NY 11042 USA. EM jbrisman@nspc.com NR 19 TC 7 Z9 7 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD FEB PY 2012 VL 81 IS 2 BP 298 EP 302 DI 10.1016/j.ejrad.2010.12.079 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 876MF UT WOS:000299110900032 PM 21316169 ER PT J AU Grudzen, CR Richardson, LD Koenig, WJ Hoffman, JR Lorenz, KA Asch, SM AF Grudzen, Corita R. Richardson, Lynne D. Koenig, William J. Hoffman, Jerome R. Lorenz, Karl A. Asch, Steven M. TI Translation of Evidence-Based Clinical Standards into a New Prehospital Resuscitation Policy in Los Angeles County SO HEALTH SERVICES RESEARCH LA English DT Article DE End-of-life; health policy; clinical practice guidelines; Emergency Medical Services ID INTENSIVE-CARE-UNIT; POSTTRAUMATIC STRESS; FAMILY-MEMBERS; CARDIAC-ARREST; INFORMATION; INDICATORS; SYMPTOMS; MAKERS AB Objective. To translate a set of evidence-based clinical standards designed to allow paramedics to forgo unnecessary and potentially harmful resuscitation attempts into a feasible new policy. Data Sources/Setting. Policy documents, meeting minutes, and personal communications between a large urban Emergency Medical Services (EMS) agency serving all of Los Angeles County (LAC) and a research group were reviewed over 12 months. Study Design. LAC EMS and University of California, Los Angeles (UCLA) formed a partnership (the EMS-UCLA Collaborative) to develop and translate the standards into new EMS protocols. Clinical indicators considered appropriate and feasible by an expert panel were submitted to the agency for inclusion in the new policy. Findings. The Collaborative submitted the results to the LAC EMS Commission and a physician advisory group for review. Of the 41 indicators approved by the expert panel, 22 would have resulted in changes to the current policy. All six involved asking family members about or honoring written and verbal Do Not Attempt Resuscitate requests, but only 4 of the 16 indicators based on clinical characteristics were included in the new policy. Ultimately, 10 of the 22 indicators that would have changed policy were approved and implemented. Conclusions. By collaboration, a large EMS agency and a research team were able to develop and implement a revised resuscitation policy within 1 year. C1 [Grudzen, Corita R.; Richardson, Lynne D.] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Grudzen, Corita R.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Koenig, William J.] Los Angeles Cty Emergency Med Agcy, Los Angeles, CA USA. [Hoffman, Jerome R.] Univ Calif Los Angeles, Dept Emergency Med, Los Angeles, CA USA. [Hoffman, Jerome R.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Lorenz, Karl A.] VA Greater Angeles, Los Angeles, CA USA. [Asch, Steven M.] VA Palo Alto, Palo Alto, CA USA. RP Grudzen, CR (reprint author), Mt Sinai Sch Med, Dept Emergency Med, Box 1620,1 Gustave L Levy Pl, New York, NY 10029 USA. EM corita.grudzen@mssm.edu OI Grudzen, Corita/0000-0003-3039-8497 FU California Health Care Foundation; Robert Wood Johnson Clinical Scholars Program FX This work was supported by the California Health Care Foundation and the Robert Wood Johnson Clinical Scholars Program. NR 21 TC 1 Z9 1 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2012 VL 47 IS 1 BP 363 EP 379 DI 10.1111/j.1475-6773.2011.01341.x PN 2 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 875OU UT WOS:000299041600004 PM 22091960 ER PT J AU Kullgren, JT McLaughlin, CG Mitra, N Armstrong, K AF Kullgren, Jeffrey T. McLaughlin, Catherine G. Mitra, Nandita Armstrong, Katrina TI Nonfinancial Barriers and Access to Care for U.S. Adults SO HEALTH SERVICES RESEARCH LA English DT Article DE Access to care; nonfinancial barriers; health reform ID SHARED MEDICAL APPOINTMENTS; HEALTH-CARE; VETERANS; SERVICES; SATISFACTION; CHILDREN; MODEL; TELEMEDICINE; PHYSICIANS; COVERAGE AB Objective. To identify prevalences and predictors of nonfinancial barriers that lead to unmet need or delayed care among U.S. adults. Data Source. 2007 Health Tracking Household Survey. Study Design. Reasons for unmet need or delayed care in the previous 12 months were assigned to one of five dimensions in the Penchansky and Thomas model of access to care. Prevalences of barriers in each nonfinancial dimension were estimated for all adults and for adults with affordability barriers. Multivariable logistic regression models were used to estimate associations between individual, household, and insurance characteristics and barriers in each access dimension. Principal Findings. Eighteen percent of U.S. adults experienced affordability barriers and 21 percent experienced nonfinancial barriers that led to unmet need or delayed care. Two-thirds of adults with affordability barriers also reported nonfinancial barriers. Young adults, women, individuals with lower incomes, parents, and persons with at least one chronic illness had higher adjusted prevalences of nonfinancial barriers. Conclusions. Nonfinancial barriers are common reasons for unmet need or delayed care among U.S. adults and frequently coincide with affordability barriers. Failure to address nonfinancial barriers may limit the impact of policies that seek to expand access by improving the affordability of health care. C1 [Kullgren, Jeffrey T.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Robert Wood Johnson Fdn Clin Scholars, Philadelphia, PA 19104 USA. [Kullgren, Jeffrey T.; Armstrong, Katrina] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [McLaughlin, Catherine G.] Mathematica Policy Res Inc, Ann Arbor, MI USA. [McLaughlin, Catherine G.] Univ Michigan, Sch Publ Hlth, Dept Hlth Management & Policy, Ann Arbor, MI 48109 USA. [Mitra, Nandita] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Armstrong, Katrina] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Armstrong, Katrina] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Kullgren, JT (reprint author), Univ Penn, Philadelphia Vet Affairs Med Ctr, Robert Wood Johnson Fdn Clin Scholars, 1303B Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kullgren@mail.med.upenn.edu FU Brigham and Women's Hospital Department of Medicine FX These contents do not represent the views of the Department of Veterans Affairs or the United States Government. This work was supported in part by a grant from the Brigham and Women's Hospital Department of Medicine Martin Solomon Medical Education Fund. Abstracts from this study were presented at the Society of General Internal Medicine Mid-Atlantic Regional Meeting in Baltimore, MD, on March 18, 2011 and the Society of General Internal Medicine 34th Annual Meeting in Phoenix, AZ, on May 6, 2011. An abstract from this study was also presented at the Academy Health Annual Research Meeting in Seattle, WA, on June 14, 2011. No other disclosures. NR 58 TC 26 Z9 26 U1 4 U2 23 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2012 VL 47 IS 1 BP 462 EP 485 DI 10.1111/j.1475-6773.2011.01308.x PN 2 PG 24 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 875OU UT WOS:000299041600010 PM 22092449 ER PT J AU Lankiewicz, JD Yokoe, DS Olsen, MA Onufrak, F Fraser, VJ Stevenson, K Khan, Y Hooper, D Platt, R Huang, SS AF Lankiewicz, Julie D. Yokoe, Deborah S. Olsen, Margaret A. Onufrak, Fallon Fraser, Victoria J. Stevenson, Kurt Khan, Yosef Hooper, David Platt, Richard Huang, Susan S. TI Beyond 30 Days: Does Limiting the Duration of Surgical Site Infection Followup Limit Detection? SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID SURVEILLANCE; MEDICARE C1 [Lankiewicz, Julie D.; Onufrak, Fallon; Platt, Richard] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. [Lankiewicz, Julie D.; Onufrak, Fallon; Platt, Richard] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Yokoe, Deborah S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Olsen, Margaret A.; Fraser, Victoria J.] Washington Univ, Sch Med, Dept Med, Div Infect Dis, St Louis, MO 63110 USA. [Olsen, Margaret A.] Washington Univ, Sch Med, Dept Surg, Div Populat Hlth Sci, St Louis, MO 63110 USA. [Stevenson, Kurt; Khan, Yosef] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Hooper, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Huang, Susan S.] Univ Calif Irvine, Sch Med, Div Infect Dis, Irvine, CA 92717 USA. [Huang, Susan S.] Univ Calif Irvine, Sch Med, Hlth Policy Res Inst, Irvine, CA 92717 USA. RP Lankiewicz, JD (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM julie_lankiewicz@hphc.org FU NCPDCID CDC HHS [U01 CI000333, U01 CI000344, U01CI0000333, U01CI000344]; NIAID NIH HHS [K24 AI067794, K24AI067794, K01 AI065808, K01AI065808] NR 10 TC 11 Z9 12 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD FEB PY 2012 VL 33 IS 2 BP 202 EP 204 DI 10.1086/663715 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 876CS UT WOS:000299085400017 PM 22227993 ER PT J AU D'Mello, S Trauernicht, A Ryan, A Bonkowski, E Willson, T Trapnell, BC Frank, SJ Kugasathan, S Denson, LA AF D'Mello, Sharon Trauernicht, Anna Ryan, Anne Bonkowski, Erin Willson, Tara Trapnell, Bruce C. Frank, Stuart J. Kugasathan, Subra Denson, Lee A. TI Innate dysfunction promotes linear growth failure in pediatric Crohn's disease and growth hormone resistance in murine ileitis SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE granulocyte-macrophage colony stimulating factor; pediatric Crohn's disease; linear growth; caspase recruitment domain family member 15; nucleotide-binding oligomerization domain containing 2 ID INFLAMMATORY-BOWEL-DISEASE; BINDING-PROTEIN; ADULT HEIGHT; CHILDREN; RETARDATION; RECEPTOR; AUTOANTIBODIES; SEVERITY; COLITIS; ONSET AB Background: Growth failure remains a common complication of pediatric Crohn's disease (CD) and has been associated with small bowel involvement and need for surgery. We have reported that patients with elevated (=1.6 mu g/mL) granulocyte macrophage colony stimulating factor autoantibodies (GM-CSF Ab) are more likely to experience complicated ileal disease requiring surgery. We hypothesized that concurrent GM-CSF Ab and CARD15 risk allele carriage (C15(+)GMAb(+)) would be associated with growth failure in CD and growth hormone (GH) resistance in murine ileitis. Methods: We enrolled 229 pediatric CD patients at two sites and determined CARD15 genotype, serum GM-CSF Ab, and GH binding protein (GHBP), and height (HTz) and weight (WTz) z-scores at diagnosis. Ileitis was induced in card15-deficient mice by GM-CSF neutralization and nonsteroidal antiinflammatory drug (NSAID) exposure. Hepatic GH receptor (GHR) abundance and GH-dependent Stat5 activation were determined by western blot and Igf-I mRNA expression by real-time polymerase chain reaction (PCR). Results: Mean (95% confidence interval [CI]) HTz at diagnosis was reduced to -0.48 (-4.2, 2.3) in C15(+)GMAb(+) patients, compared to -0.07 (-4.9, 3.4) in disease controls (P <= 0.05). Circulating GHBP, as a marker for tissue GHR abundance, was reduced in C15(+)GMAb(+) patients. Hepatic GHR abundance, GH induction of Stat5 tyrosine phosphorylation, and Igf-I mRNA expression were reduced in male card15-deficient mice with ileitis due to GM-CSF neutralization and NSAID exposure. Conclusions: Innate dysfunction due to concurrent genetic variation in CARD15 and neutralizing GM-CSF Ab is associated with linear growth failure in pediatric CD, and hepatic GH resistance in murine ileitis. C1 [D'Mello, Sharon; Trauernicht, Anna; Ryan, Anne; Bonkowski, Erin; Willson, Tara; Trapnell, Bruce C.; Denson, Lee A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [D'Mello, Sharon; Trauernicht, Anna; Ryan, Anne; Bonkowski, Erin; Willson, Tara; Trapnell, Bruce C.; Denson, Lee A.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Willson, Tara; Denson, Lee A.] Univ Cincinnati, Dept Canc & Cell Biol, Cincinnati, OH USA. [Frank, Stuart J.] Univ Alabama, Dept Med, Med Sch Birmingham, Birmingham, AL 35294 USA. [Frank, Stuart J.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Kugasathan, Subra] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. RP Denson, LA (reprint author), MLC 2010,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM lee.denson@cchmc.org FU Crohn's & Colitis Foundation of America; Broad Medical Research Program; Integrative Morphology core of the National Institutes of Health (NIH) [1P30DK078392-01]; NIH [R01 DK078683, DK068164, T32 DK007727]; VA Merit Review grant FX Supported by the Crohn's & Colitis Foundation of America through a generous gift from the Litwin Foundation, the Broad Medical Research Program, the Integrative Morphology core of the National Institutes of Health (NIH)-supported Cincinnati Children's Hospital Research Foundation Digestive Health Center (1P30DK078392-01), NIH grants R01 DK078683 (to LD.), DK068164 (to L. D.), and T32 DK007727 (to S. D., A. T.), and a VA Merit Review grant (to S.F.). NR 25 TC 9 Z9 9 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD FEB PY 2012 VL 18 IS 2 BP 236 EP 245 DI 10.1002/ibd.21689 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 874LD UT WOS:000298957800007 PM 21337672 ER PT J AU Ustyugova, IV Zhi, L Wu, MX AF Ustyugova, Irina V. Zhi, Liang Wu, Mei X. TI Reciprocal regulation of the survival and apoptosis of Th17 and Th1 cells in the colon SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Th1 and Th17 cell subsets; IEX-1; apoptosis ID INFLAMMATORY-BOWEL-DISEASE; DEXTRAN SULFATE SODIUM; COLITIS IN-VIVO; INTESTINAL INFLAMMATION; CROHNS-DISEASE; T-LYMPHOCYTES; ULCERATIVE-COLITIS; MICE; IEX-1; GENE AB Background: The immediate early response gene X-1 (IEX-1) is a stress-inducible gene involved in the regulation of cell growth, apoptosis and inflammation. Methods: Acute colitis was induced by treatment of IEX-1 knockout (KO) and wild type (WT) control mice with dextran sulfate sodium (DSS), whereas chronic colitis was induced in Rag-/- mice by adoptive transfer of CD4(+)CD45RB(hi) T cells isolated from the two strains of mice. The diseases and responses of lamina propria lymphocytes were analyzed in the mice. Results: IEX-1 KO mice produced IL-17 in the colon significantly greater than WT control mice following DSS treatment owing to better survival and differentiation of both IL-17-secreting gamma delta T cells and Th17 cells. The altered level of IL-17 production contributed critically to the reduced colon inflammation in IEX-1 KO mice, and administration of neutralizing anti-IL-17 antibody increased susceptibility of the animal to the disease. Strikingly, in contrast to the better survival of T cells producing IL-17, lack of IEX-1 enhanced apoptosis in proinflammatory T cells producing interferon gamma (IFN-gamma). Enhanced apoptosis in Th1 cells and better survival of Th17 cells may both result in a delayed onset of colitis in Rag-/- mice receiving pathogenic CD4(+)CD45RB(hi) hi T cells isolated from IEX-1 KO animals compared to those mice transferred with WT counterparts Conclusions: The present study demonstrates the refractoriness of IEX-1 knockout (KO) mice to DSS-induced colitis and diminished pathogenesis of IEX-1-deficient CD4(+)CD45RB(hi) T cells. These data demonstrate that IEX-1 reciprocally regulates T-cell survival and apoptosis in a subset- dependent fashion. Inhibition of IEX-1 may thus offer novel strategies for colitis treatment by simultaneous induction of apoptosis in proinflammatory Th1 cells while promoting the survival and differentiation of a protective T-cell subset. C1 [Ustyugova, Irina V.; Zhi, Liang; Wu, Mei X.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol, Boston, MA 02114 USA. [Ustyugova, Irina V.; Zhi, Liang; Wu, Mei X.] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Mei X.] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Ustyugova, IV (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol, Edwards 222,50 Blossom St, Boston, MA 02114 USA. EM mwu2@partners.org FU National Institutes of Health (NIH) [AI050822, AI070785]; Crohn's & Colitis Foundation of America FX Supported by National Institutes of Health (NIH) grants AI050822 and AI070785, and a Senior Research Award from the Crohn's & Colitis Foundation of America (to M.X.W.). NR 38 TC 8 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD FEB PY 2012 VL 18 IS 2 BP 333 EP 343 DI 10.1002/ibd.21772 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 874LD UT WOS:000298957800018 PM 21618360 ER PT J AU Ochtman, AEA Ring, D AF Ochtman, Alida E. A. Ring, David TI Combined posterior and medial plate fixation of complex proximal ulna fractures SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article ID CORONOID PROCESS; ELBOW; DISLOCATIONS; OLECRANON C1 [Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr,Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr,Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Wright Medical; Stryker; Biomet FX Royalties: Wright Medical; Consultant: Wright Medical, Acumed, Skeletal Dynamics, Biomet; Research Grants: Stryker, Biomet. NR 10 TC 3 Z9 5 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD FEB PY 2012 VL 43 IS 2 BP 254 EP 256 DI 10.1016/j.injury.2011.10.018 PG 3 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 879EF UT WOS:000299311800026 PM 22075448 ER PT J AU Townsend, K Corry, JM Quigley, BH George, M AF Townsend, Kristen Corry, James M. Quigley, Beth Hogan George, Maureen TI A Feasibility Study of Q-sort to Determine Recall of Skin Test Results and Environmental Remediation Education SO JOURNAL OF ASTHMA LA English DT Article; Proceedings Paper CT Meeting on Excerpts from the Occupational and Environmental CY NOV, 2010 CL Tel Aviv Univ, Tel Aviv, ISRAEL HO Tel Aviv Univ DE African American; allergies; asthma; Q-sort; self-management; triggers; urban ID ASTHMA MANAGEMENT; ACCURACY; INTERVENTION AB Objective. Allergic asthma is common in urban minority children and evidence suggests that remediation tailored to the child's allergic profile is the most effective management strategy. The purpose of this pilot study therefore was to examine the caregiver's recall of their child's skin test results and the accuracy of planned remediation similar to 4 months after testing. Methods. Caregivers were asked to recall their child's skin test results similar to 4 months after their skin testing but before any follow-up visit. A Q-sort was then used to determine the knowledge of the recommended remediation. In this Q-sort, caregivers placed 52 cards, each representing one intervention for an indoor allergen, on a response board that prioritized the interventions. At the conclusion of the Q-sort, caregivers received feedback on the accuracy of their recall and prioritization. Results. African American caregivers (5 females; mean age 33.6) of 5 children (4 males; mean age 7.8) were enrolled. No caregiver's recall of skin test results was concordant with the actual results for type or number of allergens. Caregiver's accuracy in prioritizing strategies was 33-100% for cat dander, 40-70% for molds, 70-87% for dust mite allergens, and 100% for the one dog allergic child. Subjects preferred Q-sort to traditional methods of receiving remediation education. Conclusions. Caregivers do not accurately recall skin test results and this may, in part, impede their ability to implement appropriate interventions. A low-literacy game-style approach is a novel strategy to provide complex teaching that warrants further investigation. C1 [Quigley, Beth Hogan; George, Maureen] Univ Penn, Dept Family & Community Hlth, Sch Nursing, Philadelphia, PA 19104 USA. [Corry, James M.] Childrens Hosp Philadelphia, Div Allergy, Philadelphia, PA 19104 USA. [George, Maureen] Univ Penn, Ctr Hlth Equ Res, Sch Nursing, Philadelphia, PA 19104 USA. RP George, M (reprint author), Univ Penn, Dept Family & Community Hlth, Sch Nursing, 418 Curie Blvd, Philadelphia, PA 19104 USA. EM mgeorge@nursing.upenn.edu NR 23 TC 2 Z9 2 U1 2 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PD FEB PY 2012 VL 49 IS 1 BP 83 EP 89 DI 10.3109/02770903.2011.635832 PG 7 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 875SD UT WOS:000299054100016 PM 22124168 ER PT J AU Faraone, SV Spencer, TJ Kollins, SH Glatt, SJ Goodman, D AF Faraone, Stephen V. Spencer, Thomas J. Kollins, Scott H. Glatt, Stephen J. Goodman, David TI Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults With ADHD: An Exploratory Study SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE ADHD; dose-response; lisdexamfetamine dimesylate; amphetamine; stimulants ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND; PARALLEL-GROUP; CHILDREN; METHYLPHENIDATE; EFFICACY; MEDICATIONS; RELEASE AB Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) criteria for ADHD. Results: Nearly all participants assigned to an LDX dose achieved their assigned dose with the exception of about 4% of participants assigned to the 50 mg or 14% assigned to the 70 mg doses. Higher doses of LDX led to greater improvements in ADHD-rating scale scores, independent of prior pharmacotherapy. This was evident for both inattentive and hyperactive-impulsive symptoms. The authors found some evidence for an interaction between LDX dose and baseline severity of ADHD symptoms. Conclusion: For LDX doses between 30 and 70 mg/d, the dose-response efficacy effect for LDX is not affected by prior pharmacotherapy, but patients with a greater severity of illness may benefit more from higher doses, especially for hyperactive-impulsive symptoms. The results do not provide information about doses above 70 mg/d, which is the maximum approved dose of LDX and the highest dose studied in ADHD clinical trials. (J. of Att. Dis. 2012; 16(2) 118-127) C1 [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. [Spencer, Thomas J.] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Spencer, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. [Kollins, Scott H.] Duke Univ, Med Sch Ctr, Durham, NC USA. [Glatt, Stephen J.] SUNY Upstate Med Univ, Med Genet Res Ctr, Syracuse, NY 13210 USA. [Glatt, Stephen J.] SUNY Upstate Med Univ, Psychiat Genet Epidemiol & Neurobiol Lab, PsychGENe Lab, Syracuse, NY 13210 USA. [Goodman, David] Johns Hopkins Sch Med, Baltimore, MD USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu RI Kollins, Scott/G-2965-2012; OI Glatt, Stephen/0000-0002-0360-7567; Faraone, Stephen/0000-0002-9217-3982 FU Shire; National Institutes of Health (NIH); McNeil; Janssen; Novartis; Pfizer; Eli Lilly; Shire Laboratories; Shire Laboratories Inc; Cephalon; Eli Lilly Company; Glaxo-Smith Kline; McNeil Pharmaceutical; Novartis Pharmaceuticals; NIMH; Addrenex Pharmaceuticals; Comentis, Inc.; Shire Pharmaceuticals; NIDA; NINDS; NIEHS; EPA; New River Pharmaceuticals FX The authors have either received research support, consulting fees, or speaker's fees from Shire who manufactures and distributes lisdexamfetamine.; The authors disclosed receipt of the following financial support for the research and/or authorship of this article: In the past year, Dr. Faraone received consulting fees and was on Advisory Boards for Shire Development and received research support from Shire and the National Institutes of Health (NIH). In previous years, he received consulting fees or was on Advisory Boards or participated in continuing medical education programs sponsored by Shire, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. In previous years, he received research support from Eli Lilly, Shire, Pfizer and the NIH. Dr. Faraone receives royalties from a book published by Guilford Press: Straight Talk About Your Child's Mental Health. Dr. Stephen Glatt is currently receiving research support from the National Institutes of Health. In previous years, Dr. Glatt has received research support, consulting fees or has been a speaker for the following sources: Shire Laboratories, and the National Institutes of Health. Dr. Thomas Spencer receives research support from the following sources: Shire Laboratories Inc, Cephalon, Eli Lilly & Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, Novartis Pharmaceuticals, Pfizer, and NIMH. Dr. Thomas Spencer is a speaker for the following speaker's bureaus: Shire Laboratories, Inc, Eli Lilly & Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, Novartis Pharmaceuticals. Dr. Thomas Spencer has been on advisory boards for the following pharmaceutical companies: Shire Laboratories Inc, Cephalon, Eli Lilly & Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, Novartis Pharmaceuticals, and Pfizer. Dr. Kollins has received research support from the following sources in the past 24 months: Addrenex Pharmaceuticals, Comentis, Inc., Shire Pharmaceuticals, NIDA, NIMH, NINDS, NIEHS, & EPA. Dr. Kollins has received consulting fees from the following sources in the past 24 months: Addrenex Pharmaceuticals, Comentis, Inc., Shire Pharmaceuticals, and NIDA. Dr. Goodman has received research support from Shire Laboratories Inc, Cephalon, Eli Lilly & Company, McNeil Pharmaceutical, New River Pharmaceuticals. Dr. Goodman is a speaker for Shire Laboratories, Inc, McNeil Pharmaceutical, Wyeth and Forest. Dr. Goodman has been on advisory boards and/or consultant to Shire Laboratories Inc, McNeil Pharmaceutical, Clinical Global Advisors, Thompson Reuters. NR 23 TC 3 Z9 3 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 J9 J ATTEN DISORD JI J. Atten. Disord. PD FEB PY 2012 VL 16 IS 2 BP 118 EP 127 DI 10.1177/1087054711403716 PG 10 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA 877ID UT WOS:000299170200004 PM 21527575 ER PT J AU Choi, J Kung, HJ Macias, CE Muratoglu, OK AF Choi, Jeeyoung Kung, Hsiang J. Macias, Celia E. Muratoglu, Orhun K. TI Highly lubricious poly(vinyl alcohol)-poly(acrylic acid) hydrogels SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE hydrogel; poly(vinyl alcohol); poly(acrylic acid); lubricity; creep; water content; annealing; cartilage ID ARTICULAR-CARTILAGE; ALCOHOL) HYDROGELS; MECHANICAL-PROPERTIES; POLY(ACRYLIC ACID); CROSS-LINKING; FRICTION; DEFECTS; SURFACE; REPAIR; KNEE AB Poly(vinyl alcohol) (PVA) hydrogels have desirable characteristics for use as artificial cartilage, such as biocompatibility, high water content, and surface lubricity. However, PVA hydrogels are not strong enough to withstand the demanding load-bearing environment in human joints. Thermal annealing can greatly improve compressive strength, but it also causes substantial loss in water content and lubricity. We demonstrated that incorporating anionic moieties of poly(acrylic acid) improves surface lubricity, whereas adding poly(ethylene-glycol) prevents pore collapse during thermal annealing, yielding a tough hydrogel with high lubricity. We also found a super-lubricous response from the gels when they were annealed in air versus argon gas. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 524532, 2012. C1 [Choi, Jeeyoung; Kung, Hsiang J.; Macias, Celia E.; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Lab, Boston, MA 02114 USA. [Choi, Jeeyoung; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Boston, MA USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Lab, Boston, MA 02114 USA. EM omuratoglu@partners.org FU Zimmer Inc.; Departmental funds FX Contract grant sponsors: Zimmer Inc., Departmental funds NR 36 TC 6 Z9 6 U1 2 U2 29 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD FEB PY 2012 VL 100B IS 2 BP 524 EP 532 DI 10.1002/jbm.b.31980 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 872EV UT WOS:000298792500026 PM 22120954 ER PT J AU Szostak, JW AF Szostak, Jack W. TI Comment Attempts to Define Life Do Not Help to Understand the Origin of Life SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Editorial Material C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute NR 1 TC 15 Z9 15 U1 4 U2 23 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD FEB PY 2012 VL 29 IS 4 BP 599 EP 600 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 876SN UT WOS:000299128100002 PM 22208251 ER PT J AU Tavakoli-Tabasi, S Bagree, A AF Tavakoli-Tabasi, Shahriar Bagree, Ameena TI A Longitudinal Cohort Study of Mucocutaneous Drug Eruptions During Interferon and Ribavirin Treatment of Hepatitis C SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE drug rash; interferon; ribavirin; eczema; hepatitis C ID NUMMULAR ECZEMA SECONDARY; PLUS RIBAVIRIN; VIRUS-INFECTION; PEGINTERFERON ALPHA-2B; COMBINATION THERAPY; CUTANEOUS REACTIONS; INITIAL TREATMENT; HYPERPIGMENTATION; PREVALENCE; PATIENT AB Goals: To describe dermatologic side effects encountered during treatment of patients with chronic hepatitis C, and analyze factors predisposing to such reactions. Background: Treatment of hepatitis C virus (HCV) infection with interferon (IFN) and ribavirin is associated with a number of mucocutaneous adverse reactions that have not been adequately studied. Study: A retrospective cohort study design was used to longitudinally describe mucocutaneous drug eruptions during IFN and ribavirin therapy in HCV-infected patients. Factors predictive of mucocutaneous eruptions were analyzed by the use of Kaplan-Meier curves and Cox proportional hazard model. Results: A total of 286 HCV-infected consecutive patients were treated with one of the IFN alpha formulations plus ribavirin. The mean age was 51.1 years (SD 5.6). There were 6 female patients. There were 5 patients who were also infected with human immunodeficiency virus (HIV). Fifty-six percent of the patients were white, 37% were African American, and 14% were Hispanic. Twenty-one percent of all study patients developed mucocutaneous drug eruptions. The most common drug eruptions were eczematous drug eruptions (48%), seborrheic dermatitis (11%), and xerosis (8%). Dermatologic eruptions were a contributing factor in the decision to discontinue antiviral treatment in 10% of cases. Use of Pegylated IFN formulations (hazard ratio = 1.86; 95% confidence interval, 1.04-3.34) and presence of HIV coinfection (hazard ratio = 4.46; 95% confidence interval, 1.61-12.92) were associated with increased rate of skin reactions. Conclusions: Mucocutaneous reactions during IFN and ribavirin treatment of hepatitis C are common and are associated with HIV infection and use of Pegylated IFN. C1 [Tavakoli-Tabasi, Shahriar] Michael E DeBakey Vet Adm Med Ctr, Houston, TX 77030 USA. [Tavakoli-Tabasi, Shahriar] Baylor Coll Med, Houston, TX 77030 USA. [Bagree, Ameena] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. RP Tavakoli-Tabasi, S (reprint author), Michael E DeBakey Vet Adm Med Ctr, 2002 Holcombe Blvd,111PC, Houston, TX 77030 USA. EM shahriar@bcm.edu FU Michael E DeBakey VA Medical Center, Houston, TX FX This work was conducted at, and was supported by the Michael E DeBakey VA Medical Center, Houston, TX. NR 24 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD FEB PY 2012 VL 46 IS 2 BP 162 EP 167 DI 10.1097/MCG.0b013e318228b5f6 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 876OZ UT WOS:000299118400013 PM 21814144 ER PT J AU Gorman, A Kaye, EK Apovian, C Fung, TT Nunn, M Garcia, RI AF Gorman, Andrea Kaye, Elizabeth Krall Apovian, Caroline Fung, Teresa T. Nunn, Martha Garcia, Raul I. TI Overweight and obesity predict time to periodontal disease progression in men SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE body mass index; obesity; overweight; periodontal disease; waist circumference; waist circumference-to-height ratio ID TO-HEIGHT RATIO; WAIST CIRCUMFERENCE; CARDIOVASCULAR RISK; UNITED-STATES; TOOTH LOSS; ADULTS; POPULATION; INDICATORS; HEALTH; ASSOCIATION AB Aims: To examine whether overweight and obesity indicators -body mass index (BMI), waist circumference (WC), and WC-to-height ratio -predict progression of periodontal disease in men. Material and Methods: Participants were 1038 medically healthy, non-Hispanic, white males in the VA Dental Longitudinal Study who were monitored with triennial oral and medical examinations between 1969 and 1996. Periodontal disease progression in an individual was defined as having two or more teeth advance to levels of alveolar bone loss >= 40%, probing pocket depth similar to 5 mm, or clinical attachment loss > 5 mm after baseline. Extended Cox regression analyses estimated hazards of experiencing periodontal disease progression events due to overweight/ obesity status, controlling for age, smoking, education, diabetes, recent periodontal treatment, recent prophylaxis, and number of filled/ decayed surfaces. Results: Body mass index and WC-to-height ratio were significantly associated with hazards of experiencing periodontal disease progression events regardless of periodontal disease indicator. Adjusted hazard ratios for periodontal disease progression were 41-72% higher in obese men (BMI >= 30 kg/m(2)) relative to men with both normal weight and WC-to-height ratio (>= 50%). Conclusion: Both overall obesity and central adiposity are associated with an increased hazards of periodontal disease progression events in men. C1 [Gorman, Andrea; Apovian, Caroline] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kaye, Elizabeth Krall; Garcia, Raul I.] Boston Univ, Dept Hlth Policy, Henry M Goldman Sch Dent Med, Boston, MA 02118 USA. [Fung, Teresa T.] Simmons Coll, Sch Nutr, Boston, MA 02115 USA. [Nunn, Martha] Creighton Univ, Sch Dent, Omaha, NE 68178 USA. [Garcia, Raul I.] VA Boston Healthcare Syst, Boston, MA USA. RP Gorman, A (reprint author), Boston Univ, Sch Med, 72 E Concord St, Boston, MA 02118 USA. EM agorman@lifespan.org OI Apovian, Caroline/0000-0002-8029-1922; Garcia, Raul/0000-0003-2153-4629; Kaye, Elizabeth/0000-0001-7529-2501 FU US Department of Veterans Affairs; VA Health Services Research and Development Service; National Institute of Dental and Craniofacial Research [R01 DE019833, K24 DE00419] FX The Dental Longitudinal Study and Normative Aging Study are components of the Massachusetts Veterans Epidemiology Research and Information Center which is supported by the US Department of Veterans Affairs Cooperative Studies Program. Dr Garcia was a recipient of a Veterans Affairs Career Development Award in Health Services Research from the VA Health Services Research and Development Service. This study was supported by National Institute of Dental and Craniofacial Research R01 DE019833 and K24 DE00419. The views expressed in this paper are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. NR 34 TC 43 Z9 44 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD FEB PY 2012 VL 39 IS 2 BP 107 EP 114 DI 10.1111/j.1600-051X.2011.01824.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 875XZ UT WOS:000299070000001 PM 22150475 ER PT J AU Kirchner, JE Parker, LE Bonner, LM Fickel, JJ Yano, EM Ritchie, MJ AF Kirchner, JoAnn E. Parker, Louise E. Bonner, Laura M. Fickel, Jacqueline J. Yano, Elizabeth M. Ritchie, Mona J. TI Roles of managers, frontline staff and local champions, in implementing quality improvement: stakeholders' perspectives SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article DE champions; frontline providers; implementation; managers; primary care; mental health; quality improvement ID PRACTICE GUIDELINES; OPINION LEADERS; HEALTH-CARE; CONCEPTUAL-FRAMEWORK; PARTICIPATION; SATISFACTION; KNOWLEDGE; TAXONOMY; SYSTEMS; WORK AB Background Translating promising research findings into routine clinical care has proven difficult to achieve; even highly efficacious programmes remain unadopted. Critical to changing care is an understanding of the context within which the improvement effort occurs, including the climate or culture. Health care systems are multicultural due to the wide variety of professionals, subgroups, divisions and teams within them. Yet, little work describes and compares different stakeholders' views on their and others' roles in promoting successful quality improvement implementation. C1 [Kirchner, JoAnn E.; Parker, Louise E.; Ritchie, Mona J.] HSR&D Ctr Mental Healthcare & Outcomes Res, N Little Rock, AR 72114 USA. [Kirchner, JoAnn E.; Parker, Louise E.; Ritchie, Mona J.] Mental Hlth Qual Enhancement Res Initiat, N Little Rock, AR USA. [Kirchner, JoAnn E.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Bonner, Laura M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Bonner, Laura M.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Fickel, Jacqueline J.; Yano, Elizabeth M.] Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Kirchner, JE (reprint author), HSR&D Ctr Mental Healthcare & Outcomes Res, 2200 Ft Roots Dr,Bldg 58, N Little Rock, AR 72114 USA. EM kirchnerjoanne@uams.edu FU Cost and Value of Evidenced-Based Solutions for Depression Study (COVES) [MNT 02-209]; VA HSR&D Research Career Scientist award [05-195] FX Work on this manuscript was supported by the Cost and Value of Evidenced-Based Solutions for Depression Study (COVES) MNT 02-209. Dr Yano's time is supported by VA HSR&D Research Career Scientist award (Project #05-195). We would like to thank Lisa Rubenstein, MD, MPH, and Edmund Chaney, PhD, for their leadership on TIDES Implementation, Geoffrey Curran, PhD, for his review, Penny White for her administrative support, and Valorie Shue for her assistance with editing the manuscript. NR 43 TC 14 Z9 14 U1 1 U2 21 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1356-1294 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD FEB PY 2012 VL 18 IS 1 BP 63 EP 69 DI 10.1111/j.1365-2753.2010.01518.x PG 7 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA 872XL UT WOS:000298844600011 PM 20738467 ER PT J AU Bishop, AL Tarique, AA Patimalla, B Calderwood, SB Qadri, F Camilli, A AF Bishop, Anne L. Tarique, Abdullah A. Patimalla, Bharathi Calderwood, Stephen B. Qadri, Firdausi Camilli, Andrew TI Immunization of Mice With Vibrio cholerae Outer-Membrane Vesicles Protects Against Hyperinfectious Challenge and Blocks Transmission SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SUCKLING MOUSE MODEL; TOXR REGULON; EL-TOR; IMMUNITY; VACCINE; EXPRESSION; ANTIBODIES; INFECTION; VIRULENCE; EFFICACY AB Background. Vibrio cholerae excreted by cholera patients is "hyperinfectious'' ( HI), which can be modeled by passage through infant mice. Immunization of adult female mice with V. cholerae outer-membrane vesicles (OMVs) passively protects suckling mice from challenge. Although V. cholerae is unable to colonize protected pups, the bacteria survive passage and have the potential to be transmitted to susceptible individuals. Here, we investigated the impact of OMV immunization and the HI state on V. cholerae transmission. Methods. Neonatal mice suckled by OMV- or sham-immunized dams were challenged with HI V. cholerae. The infectivity of spatially and temporally separate V. cholerae populations obtained from infected naive or protected pups was tested. Recombination-based in vivo expression technology was used to assess virulence gene expression within these populations. Results. OMV immunization significantly reduced colonization of neonates challenged with HI V. cholerae. Vibrio cholerae that had colonized the naive host was HI, whereas V. cholerae excreted by neonates born to OMV-immunized dams, although viable, was hypoinfectious and failed to fully induce virulence gene expression. Conclusions. OMV immunization can significantly reduce the V. cholerae burden upon challenge with HI V. cholerae and can also block transmission from immune mice by reducing the infectivity of shed bacteria. C1 [Bishop, Anne L.; Patimalla, Bharathi; Camilli, Andrew] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Bishop, Anne L.; Patimalla, Bharathi; Camilli, Andrew] Howard Hughes Med Inst, Boston, MA 02111 USA. [Tarique, Abdullah A.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Div Sci Lab, Dhaka 1000, Bangladesh. [Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Tarique, Abdullah A.] Erasmus MC, Dept Immunol, Rotterdam, Netherlands. RP Camilli, A (reprint author), Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. EM andrew.camilli@tufts.edu RI Tarique, Abdullah/M-2860-2013 OI Tarique, Abdullah/0000-0003-3782-345X FU US National Institutes of Health (NIH) [AI055058]; NIH [AI058935] FX This work was supported by the US National Institutes of Health (NIH) grant AI055058 awarded to A. C. and NIH grant AI058935 to S. B. C. A. C. is a Howard Hughes Medical Institute investigator. NR 23 TC 18 Z9 19 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2012 VL 205 IS 3 BP 412 EP 421 DI 10.1093/infdis/jir756 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 876HA UT WOS:000299097200010 PM 22147790 ER PT J AU Duailibi, MT Kulikowski, LD Duailibi, SE Lipay, MVN Melaragno, MI Ferreira, LM Vacanti, JP Yelick, PC AF Duailibi, Monica Talarico Kulikowski, Leslie Domenici Duailibi, Silvio Eduardo Nunes Lipay, Monica Vannucci Melaragno, Maria Isabel Ferreira, Lydia Masako Vacanti, Joseph Phillip Yelick, Pamela Crotty TI Cytogenetic instability of dental pulp stem cell lines SO JOURNAL OF MOLECULAR HISTOLOGY LA English DT Article DE Chromosomal abnormalities; Cell transplantation; Tooth tissue engineering; Human dental stem cells ID CHROMOSOME STABILITY; NUCLEAR TRANSFER; IN-VITRO; CULTURE; ABNORMALITIES; POPULATION; KARYOTYPE; INTEGRITY; TOOTH; BONE AB Human adult stem cells (hASCs) offer a potentially renewable source of cell types that are easily isolated and rapidly expanded for use in regenerative medicine and cell therapies without the complicating ethical problems that are associated with embryonic stem cells. However, the eventual therapeutic use of hASCs requires that these cells and their derivatives maintain their genomic stability. There is currently a lack of systematic studies that are aimed at characterising aberrant chromosomal changes in cultured ASCs over time. However, the presence of mosaicism and accumulation of karyotypic abnormalities within cultured cell subpopulations have been reported. To investigate cytogenetic integrity of cultured human dental stem cell (hDSC) lines, we analysed four expanded hDSC cultures using classical G banding and fluorescent in situ hybridisation (FISH) with X chromosome specific probe. Our preliminary results revealed that about 70% of the cells exhibited karyotypic abnormalities including polyploidy, aneuploidy and ring chromosomes. The heterogeneous spectrum of abnormalities indicates a high frequency of chromosomal mutations that continuously arise upon extended culture. These findings emphasise the need for the careful analysis of the cytogenetic stability of cultured hDSCs before they can be used in clinical therapies. C1 [Kulikowski, Leslie Domenici] Univ Sao Paulo, Dept Pathol, Cytogenom Lab, BR-05403000 Sao Paulo, Brazil. [Duailibi, Monica Talarico; Duailibi, Silvio Eduardo; Ferreira, Lydia Masako] Univ Fed Sao Paulo, Dept Plast Surg, Ctr Cellular & Mol Therapy, UNIFESP CTCMol, Sao Paulo, Brazil. [Duailibi, Monica Talarico; Duailibi, Silvio Eduardo] INCT Biofabris, Natl Inst Sci & Technol, Biofabricat Inst, Sao Paulo, Brazil. [Duailibi, Silvio Eduardo] UNIFESP Sao Jose Campos, Sci & Technol Inst Biomed Engn, Sao Paulo, Brazil. [Nunes Lipay, Monica Vannucci] Univ Fed Sao Paulo, Div Endocrinol, Sao Paulo, Brazil. [Vacanti, Joseph Phillip] Massachusetts Gen Hosp, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. [Vacanti, Joseph Phillip] Harvard Univ, Sch Med, Boston, MA USA. [Vacanti, Joseph Phillip] Dept Surg, Boston, MA USA. [Yelick, Pamela Crotty] Tufts Univ, Dept Oral & Maxillofacial Pathol, Boston, MA 02111 USA. RP Kulikowski, LD (reprint author), Univ Sao Paulo, Dept Pathol, Cytogenom Lab, LIM 03,Av Dr Ene Carvalho Aguiar 255, BR-05403000 Sao Paulo, Brazil. EM lesliekulik@hc.usp.br RI Lipay, Monica/C-4867-2012; Ferreira, Lydia/B-7511-2012; Kulikowski, Leslie/F-4524-2012; Biofabris, Inct/I-2418-2013; Melaragno, Maria/F-9013-2012 OI Kulikowski, Leslie/0000-0003-2236-3956; FU INCT-Biofabrication Institute; CNPq [573661/2008-1]; FAPESP [08/57860-3, 07-58856-7, 07-51227-4, 07-59488-1]; Rede Biofab, Ibero-American Network of Biofabrication-BIOFAB-CYTED [208RT0340]; NIH/NIDCR [R01DE016132, R03TW007665] FX We wish to thank the INCT-Biofabrication Institute, CNPq 573661/2008-1, FAPESP 08/57860-3, and the Rede Biofab, Ibero-American Network of Biofabrication-BIOFAB-CYTED (208RT0340). This work was supported by FAPESP grants 07-58856-7, 07-51227-4, 07-59488-1, and NIH/NIDCR R01DE016132 (PCY), and R03TW007665 (PCY, MTD, SED) awards. We are also grateful to Dr. Waldyr Antonio Jorge, Ph.D., Oral Maxillofacial Surgery Course of Dental School, FFO-FOUSP Professor of University of Sao Paulo for contribution of the biological material access. NR 30 TC 4 Z9 4 U1 0 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1567-2379 J9 J MOL HISTOL JI J. Mol. Histol. PD FEB PY 2012 VL 43 IS 1 BP 89 EP 94 DI 10.1007/s10735-011-9373-z PG 6 WC Cell Biology SC Cell Biology GA 880AL UT WOS:000299376400011 PM 22109772 ER PT J AU Agudelo, JF Flierl, MA Smith, WR Moore, EE Williams, AE Eckels, PC Morgan, SJ Stahel, PF AF Agudelo, Juan F. Flierl, Michael A. Smith, Wade R. Moore, Ernest E. Williams, Allison E. Eckels, Philip C. Morgan, Steven J. Stahel, Philip F. TI Influence of Preoperative 7.5% Hypertonic Saline on Neutrophil Activation After Reamed Intramedullary Nailing of Femur Shaft Fractures: A Prospective Randomized Pilot Study SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE hypertonic saline; intramedullary nailing; femur shaft fracture; neutrophil ID MULTIPLE ORGAN FAILURE; RESPIRATORY-DISTRESS-SYNDROME; INFLAMMATORY RESPONSE SYNDROME; TRAUMATIC HEMORRHAGIC-SHOCK; CONTROL ORTHOPEDIC-SURGERY; L-SELECTIN; DAMAGE CONTROL; CYTOTOXIC RESPONSE; FEMORAL FRACTURES; HYPOVOLEMIC SHOCK AB Objectives: Femoral reaming and intramedullary nailing (IMN) primes polymorphonuclear leukocytes (PMNL) and thereby increases the posttraumatic systemic inflammatory response. Resuscitation with hypertonic saline (HTS) attenuates PMNL activation after trauma-hemorrhage. We hypothesized that preoperative administration of 7.5% HTS attenuates PMNL priming after IMN of unilateral femur shaft fractures compared with 0.9% normal saline. Design: Prospective, randomized, double-blind study. Setting: Level I trauma center. Patients: Twenty patients between 18 and 80 years of age with an Injury Severity Score less than 25 and a unilateral femur shaft fracture amenable to IMN fixation within 24 hours after injury. Intervention: Patients were allocated to equally sized HTS or normal saline treatment groups (n = 10) before surgery. Solutions were administered in a blinded bag as a single bolus of 4 mL/kg body weight immediately before surgery. Whole blood samples were collected directly before saline application (t(0)) and at 6, 12, and 24 hours after surgery. Main Outcome Measurements: PMNL surface expression of CD11b and CD62L, as determined by flow cytometry analysis. Results: Demographic characteristics of both treatment groups were comparable. Baseline expression of CD11b and CD62L cell markers was in a similar range in the two cohorts. The expression levels of CD11b were comparable between the two groups throughout the observation time, whereas CD62L levels were significantly higher in the HTS group at 6 and 24 hours after surgery. Conclusion and Significance: Preoperative infusion of HTS appears to exert an anti-inflammatory effect by attenuating the extent of postoperative PMNL activation after reamed IMN for femoral shaft fractures. C1 [Stahel, Philip F.] Univ Colorado, Sch Med, Denver Hlth Med Ctr, Dept Orthopaed Surg,Dept Neurosurg, Denver, CO 80204 USA. [Smith, Wade R.] Geisinger Med Ctr, Dept Orthopaed Surg, Danville, PA 17822 USA. [Williams, Allison E.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Stahel, PF (reprint author), Univ Colorado, Sch Med, Denver Hlth Med Ctr, Dept Orthopaed Surg,Dept Neurosurg, 777 Bannock St, Denver, CO 80204 USA. EM philip.stahel@dhha.org FU Orthopaedic Trauma Association (OTA) FX This study was supported by a grant from the Orthopaedic Trauma Association (OTA). NR 67 TC 4 Z9 4 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD FEB PY 2012 VL 26 IS 2 BP 86 EP 91 DI 10.1097/BOT.0b013e31821cfd2a PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 877RQ UT WOS:000299200000010 PM 21904224 ER PT J AU Laggner, C Kokel, D Setola, V Tolia, A Lin, H Irwin, JJ Keiser, MJ Cheung, CYJ Minor, DL Roth, BL Peterson, RT Shoichet, BK AF Laggner, Christian Kokel, David Setola, Vincent Tolia, Alexandra Lin, Henry Irwin, John J. Keiser, Michael J. Cheung, Chung Yan J. Minor, Daniel L., Jr. Roth, Bryan L. Peterson, Randall T. Shoichet, Brian K. TI Chemical informatics and target identification in a zebrafish phenotypic screen SO NATURE CHEMICAL BIOLOGY LA English DT Article ID SMALL MOLECULES; PHARMACOLOGY AB Target identification is a core challenge in chemical genetics. Here we use chemical similarity to computationally predict the targets of 586 compounds that were active in a zebrafish behavioral assay. Among 20 predictions tested, 11 compounds had activities ranging from 1 nM to 10,000 nM on the predicted targets. The roles of two of these targets were tested in the original zebrafish phenotype. Prediction of targets from chemotype is rapid and may be generally applicable. C1 [Setola, Vincent; Roth, Bryan L.] Univ N Carolina Chapel Hill Sch Med, Dept Pharmacol, Chapel Hill, NC 27515 USA. [Laggner, Christian; Lin, Henry; Irwin, John J.; Keiser, Michael J.; Shoichet, Brian K.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA USA. [Kokel, David; Cheung, Chung Yan J.; Peterson, Randall T.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Dept Med,Massachusetts Gen Hosp, Charlestown, MA USA. [Kokel, David; Cheung, Chung Yan J.; Peterson, Randall T.] Harvard Univ, Sch Med, Div Cardiol, Dept Med,Massachusetts Gen Hosp, Charlestown, MA USA. [Kokel, David; Cheung, Chung Yan J.; Peterson, Randall T.] Broad Inst, Cambridge, MA USA. [Setola, Vincent; Roth, Bryan L.] Univ N Carolina Chapel Hill Sch Med, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Chapel Hill, NC USA. [Tolia, Alexandra; Minor, Daniel L., Jr.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Tolia, Alexandra; Minor, Daniel L., Jr.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. RP Roth, BL (reprint author), Univ N Carolina Chapel Hill Sch Med, Dept Pharmacol, Chapel Hill, NC 27515 USA. EM bryan_roth@med.unc.edu; peterson@cvrc.mgh.harvard.edu; shoichet@cgl.ucsf.edu RI Roth, Bryan/F-3928-2010; Keiser, Michael/F-2825-2016; OI Keiser, Michael/0000-0002-1240-2192; kokel, david/0000-0002-1981-1511; Irwin, John/0000-0002-1195-6417 FU US National Institutes of Health [GM71896, AG02132, MH085205, MH086867, MH091449, R01 MH093603, R01 NS49272]; Rogers Family Foundation; National Institutes of Mental Health [U19MH82441]; Michael Hooker Chair; Max Kade Foundation; European Molecular Biology Organization FX We thank S. Morris for help with Cytoscape. This work was supported by US National Institutes of Health grants GM71896 (to J.J.I. and B.K.S.), AG02132 (to S. Prusiner and B.K.S.), MH085205 and MH086867 (to R.P.), MH091449 (to D.K.), R01 MH093603 and R01 NS49272 (to D.L.M.); a Rogers Family Foundation award (to M.J.K.); the National Institutes of Mental Health Psychoactive Drug Screening Program, grant U19MH82441; the Michael Hooker Chair (to B.L.R.); and fellowships from the Max Kade Foundation (to C.L.) and the European Molecular Biology Organization (to A.T.). NR 25 TC 63 Z9 63 U1 3 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD FEB PY 2012 VL 8 IS 2 BP 144 EP 146 DI 10.1038/nchembio.732 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 879IP UT WOS:000299323200005 PM 22179068 ER PT J AU Typas, A Banzhaf, M Gross, CA Vollmer, W AF Typas, Athanasios Banzhaf, Manuel Gross, Carol A. Vollmer, Waldemar TI From the regulation of peptidoglycan synthesis to bacterial growth and morphology SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID D-AMINO ACIDS; DAUGHTER CELL-SEPARATION; ATOMIC-FORCE MICROSCOPY; ESCHERICHIA-COLI-CELLS; DIVISION PROTEIN FTSN; PENICILLIN-BINDING PROTEINS; GRAM-NEGATIVE BACTERIA; TOL-PAL COMPLEX; CAULOBACTER-CRESCENTUS; BACILLUS-SUBTILIS AB How bacteria grow and divide while retaining a defined shape is a fundamental question in microbiology, but technological advances are now driving a new understanding of how the shape-maintaining bacterial peptidoglycan sacculus grows. In this Review, we highlight the relationship between peptidoglycan synthesis complexes and cytoskeletal elements, as well as recent evidence that peptidoglycan growth is regulated from outside the sacculus in Gram-negative bacteria. We also discuss how growth of the sacculus is sensitive to mechanical force and nutritional status, and describe the roles of peptidoglycan hydrolases in generating cell shape and of D-amino acids in sacculus remodelling. C1 [Vollmer, Waldemar] Newcastle Univ, Inst Cell & Mol Biosci, Ctr Bacterial Cell Biol, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England. [Typas, Athanasios; Gross, Carol A.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [Typas, Athanasios] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany. [Banzhaf, Manuel] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Gross, Carol A.] Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94158 USA. RP Vollmer, W (reprint author), Newcastle Univ, Inst Cell & Mol Biosci, Ctr Bacterial Cell Biol, Richardson Rd, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England. EM w.vollmer@ncl.ac.uk OI Banzhaf, Manuel/0000-0002-4682-1037; Typas, Athanasios/0000-0002-0797-9018 FU UK Biotechnology and Biological Sciences Research Council [BB/G015902/1, BBI020012/1]; European Commission [DIVINOCELL HEALTH-F3-2009-223,431]; Royal Society; US National Institutes of Health [R01 GM085697, ARRA GM085697-01S1, R01 GM036278, K99GM092984] FX This work was supported by grants from the UK Biotechnology and Biological Sciences Research Council (BB/G015902/1 and BBI020012/1 to W. V.), the European Commission (DIVINOCELL HEALTH-F3-2009-223,431 to W. V.), the Royal Society (to W. V.) and the US National Institutes of Health (R01 GM085697, ARRA GM085697-01S1 and R01 GM036278 to C. A. G., and K99GM092984 to A.T.). NR 138 TC 271 Z9 274 U1 31 U2 200 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 FEB PY 2012 VL 10 IS 2 BP 123 EP 136 DI 10.1038/nrmicro2677 PG 14 WC Microbiology SC Microbiology GA 876NS UT WOS:000299115000012 ER PT J AU Xie, PX Kranzler, HR Zhang, HP Oslin, D Anton, RF Farrer, LA Gelernter, J AF Xie, Pingxing Kranzler, Henry R. Zhang, Huiping Oslin, David Anton, Raymond F. Farrer, Lindsay A. Gelernter, Joel TI Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with alpha 5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE CHRNA5; childhood adversity; gene-environment interaction; nicotine dependence; Fagerstrom test for nicotine dependence score ID GENOMEWIDE LINKAGE SCAN; SEMISTRUCTURED ASSESSMENT; EPIGENETIC REGULATION; POSTTRAUMATIC-STRESS; ALCOHOLISM SSADDA; OPIOID DEPENDENCE; SMOKING-BEHAVIOR; DRUG-DEPENDENCE; SEX-DIFFERENCES; ABUSE AB The relative importance of specific genetic and environmental factors in regulating nicotine dependence (ND) risk, including the effects on specific forms of childhood adversity on smoking risk, have been understudied. Genome-wide association studies and rodent models have demonstrated that the alpha 5 nicotinic acetylcholine receptor gene (CHRNA5) is important in regulating nicotine intake. Childhood adversity increases the methylation level of the CHRNA5 promoter region in European Americans (EAs), an effect that was observed only in males (Zhang et al, submitted for publication). In view of this potential sex difference in the effects of early life experience on smoking, we investigated the presence of a sex-specific gene-by-environment effect of this marker on ND risk. A nonsynonymous SNP in CHRNA5 previously associated to ND and several related traits, rs16969968, was genotyped in 2206 EAs (1301 men and 905 women). The main and interactive effects of childhood adversity and rs16969968 genotype on diagnosis of ND and ND defined by dichotomized Fagerstrom test for ND (FTND) scores were explored. Men and women were analyzed separately to test for sex differences. Childhood adversity significantly increased ND risk in both sexes, and the effect in women was twice than that in men. Significant interactive effects of childhood adversity and rs16969968 genotype were observed in men (ND: OR = 1.80, 95% CI = 1.18-2.73, P = 0.0044; FTND: OR = 1.79, 95% CI = 1.11-2.88, P = 0.012). No interaction was found in women. This study provides evidence of a sex-specific gene x environment effect of CHRNA5 and childhood adversity on the risk for ND. Neuropsychopharmacology (2012) 37, 669-676; doi: 10.1038/npp.2011.240; published online 19 October 2011 C1 [Xie, Pingxing; Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Xie, Pingxing; Zhang, Huiping; Gelernter, Joel] VA CT Healthcare Ctr, West Haven, CT USA. [Kranzler, Henry R.; Oslin, David] Univ Penn, Dept Psychiat, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Zhang, Huiping; Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Anton, Raymond F.] Med Univ S Carolina, Dept Psychiat, Ctr Alcohol & Drug Programs, Charleston, SC 29425 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Med, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Ophthalmol, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Genet & Genom, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Gelernter, J (reprint author), Yale Univ, Sch Med, Dept Psychiat, Div Human Genet Psychiat,VA CT Healthcare Ctr 116, 950 Campbell Ave, West Haven, CT 06516 USA. EM joel.gelernter@yale.edu OI Farrer, Lindsay/0000-0001-5533-4225 FU NIH [R01 DA12690, R01 DA12849, R01 AA11330]; Alkermes; GlaxoSmithKline; Gilead; Lundbeck; Merck; Eli Lilly; Janssen; Schering Plough; Abbott; Johnson Johnson; ACTIVE FX We thank the individuals and families participating in this work and the interviewers at all the participating sites for collecting the data. This study was supported by NIH Grants R01 DA12690, R01 DA12849, and R01 AA11330.; Dr Kranzler has received consulting fees from Alkermes, GlaxoSmithKline, Gilead, and Lundbeck and research support from Merck. Dr Anton reports for the last 2 years, being a consultant for Eli Lilly, GlaxoSmithKline, and Alkermes. Drs Kranzler and Anton also report associations with Eli Lilly, Merck, Janssen, Schering Plough, Lundbeck, Alkermes, GlaxoSmithKline, Abbott, and Johnson & Johnson, as these companies provide support to the ACNP Alcohol Clinical Trials Initiative (ACTIVE) and they receive support from ACTIVE. Dr Gelernter reports that he has received compensation for professional services in the previous 3 years from the following entities: Yale University School of Medicine, Veterans Affairs Healthcare System (VA), and the National Institutes of Health (NIAAA, NIDA, and NIMH), and related to academic lectures and editorial functions in various scientific venues (including the ACNP). The other authors declared no conflict of interest. NR 45 TC 18 Z9 18 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2012 VL 37 IS 3 BP 669 EP 676 DI 10.1038/npp.2011.240 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 876OV UT WOS:000299117900009 PM 22012472 ER PT J AU Hoexter, MQ Duran, FLD D'Alcante, CC Dougherty, DD Shavitt, RG Lopes, AC Diniz, JB Deckersbach, T Batistuzzo, MC Bressan, RA Miguel, EC Busatto, GF AF Hoexter, Marcelo Queiroz de Souza Duran, Fabio Luis D'Alcante, Carina Chaubet Dougherty, Darin Dean Shavitt, Roseli Gedanke Lopes, Antonio Carlos Diniz, Juliana Belo Deckersbach, Thilo Batistuzzo, Marcelo Camargo Bressan, Rodrigo Affonseca Miguel, Euripedes Constantino Busatto, Geraldo Filho TI Gray Matter Volumes in Obsessive-Compulsive Disorder Before and After Fluoxetine or Cognitive-Behavior Therapy: A Randomized Clinical Trial SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE OCD; neuroimaging; magnetic resonance imaging; serotonin reuptake inhibitors; cognitive-behavior therapy; randomized clinical trial ID VENTROMEDIAL PREFRONTAL CORTEX; VOXEL-BASED MORPHOMETRY; CEREBRAL-BLOOD-FLOW; SEROTONIN REUPTAKE INHIBITORS; GLUCOSE METABOLIC-RATE; FEAR EXTINCTION; MAJOR DEPRESSION; CELL-PROLIFERATION; PEDIATRIC-PATIENTS; HUMAN BRAIN AB Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n = 38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n = 36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n = 26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n = 13), whereas no significant GM volume changes were observed in CBT-treated patients (n = 13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action. Neuropsychopharmacology (2012) 37, 734-745; doi: 10.1038/npp.2011.250; published online 26 October 2011 C1 [Hoexter, Marcelo Queiroz; de Souza Duran, Fabio Luis; D'Alcante, Carina Chaubet; Shavitt, Roseli Gedanke; Lopes, Antonio Carlos; Diniz, Juliana Belo; Batistuzzo, Marcelo Camargo; Miguel, Euripedes Constantino; Busatto, Geraldo Filho] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. [Hoexter, Marcelo Queiroz; de Souza Duran, Fabio Luis; D'Alcante, Carina Chaubet; Shavitt, Roseli Gedanke; Lopes, Antonio Carlos; Diniz, Juliana Belo; Batistuzzo, Marcelo Camargo; Miguel, Euripedes Constantino; Busatto, Geraldo Filho] Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. [Hoexter, Marcelo Queiroz; Bressan, Rodrigo Affonseca] Univ Fed Sao Paulo UNIFESP, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LiNC, Sao Paulo, Brazil. [Hoexter, Marcelo Queiroz; Dougherty, Darin Dean; Deckersbach, Thilo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Hoexter, MQ (reprint author), Ctr Med Nucl HC FMUSP, Lab Neuroimagem Psiquiatria LIM2I, Rua Ovidio Pires Campos S-N,3 Andar, BR-05403911 Sao Paulo, Brazil. EM mqhoexter@gmail.com RI Miguel, Euripedes/B-2871-2008; Hoexter, Marcelo/D-7620-2013; Diniz, Juliana/D-2503-2011; Duran, Fabio/A-9744-2013; Busatto, Geraldo/D-4431-2009; Duran, Fabio/L-1371-2013; Duran, Fabio/I-5704-2012; Bressan, Rodrigo/E-9178-2010; Batistuzzo, Marcelo/H-7790-2015 OI Hoexter, Marcelo/0000-0002-9302-4380; Diniz, Juliana/0000-0001-9486-3779; Duran, Fabio/0000-0002-7603-6152; Duran, Fabio/0000-0002-7603-6152; Duran, Fabio/0000-0003-2494-7250; Bressan, Rodrigo/0000-0002-0868-4449; FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo) [2005/55628-8]; FAPESP [06/61459-7, 06/50273-0, 2008/10257-0, 06/58286-3, 2005/04206-6]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Agency for Support and Evaluation of Graduate Education) [4375/08-4]; Medtronic; Eli Lilly; McNeil; Cyberonics; NIMH; NARSAD; TSA; OCF; Tufts University; MGH Psychiatry Academy; BrainCells; Systems Research and Applications Corporation; Boston University; Catalan Agency for Health Technology Assessment and Research; National Association of Social Workers Massachusetts; Massachusetts Medical Society; NIDA; German Research Foundation/Federal Ministry for Education and Research; Oxford University Press; NIH; NIA; AHRQ; Janssen Pharmaceuticals; Forest Research Institute; Shire Development; Northstar; Janssen; AstraZeneca; Lundbeck; Solvay FX We thank Dr Cristina Belotto-Silva, Ms Sonia Borcatto, Dr Ana Gabriela Hounie, Ms Marines Alves Joaquim, Ms Ana Carolina Ferreira Rosa, and Ms Luciana Cristina Santos whose help was critical to the conduction of this project. We also thank Ms Dianne M Hezel for helpful comments on the manuscript. This study received financial support in the form of grants provided by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo) to Dr Miguel (2005/55628-8) and from FAPESP scholarships to Dr Shavitt (06/61459-7), to Dr Diniz (06/50273-0), to Dr Lopes (2008/10257-0), and to Ms D'Alcante (06/58286-3). Dr Hoexter is supported by a PhD scholarship from FAPESP (2005/04206-6) and by a doctorate 'sandwich' scholarship from the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Agency for Support and Evaluation of Graduate Education) (4375/08-4). This work was presented in part at the 48th Annual Meeting of the American College of Neuropsychopharmacology, 6-10 December 2009, Hollywood, Florida, USA.; Dr Hoexter, Dr Duran, Ms D'Alcante, Dr Shavitt, Dr Lopes, Dr Diniz, Mr Batistuzzo, and Dr Busatto have declared no conflict of interest. Dr Dougherty has acted as a consultant for Medtronic, Eli Lilly, Brand Ideas, McNeil, and Reed Elsevier, and has received research funding from Medtronic, Eli Lilly, McNeil, and Cyberonics. Dr Deckersbach's research has been funded by NIMH, NARSAD, TSA, OCF, and Tufts University. He has received honoraria, consultation fees, and/or royalties from the MGH Psychiatry Academy, BrainCells, Systems Research and Applications Corporation, Boston University, the Catalan Agency for Health Technology Assessment and Research, the National Association of Social Workers Massachusetts, the Massachusetts Medical Society, Tufts University, NIDA, German Research Foundation/Federal Ministry for Education and Research, and Oxford University Press. He has also participated in research funded by NIH, NIA, AHRQ, Janssen Pharmaceuticals, The Forest Research Institute, Shire Development, Medtronic, Cyberonics, and Northstar. Dr Bressan has received honoraria and/or consultations fees from Novartis, Eli Lilly, Janssen, and AstraZeneca. Dr Miguel has received lecture fees from Lundbeck and Solvay. NR 80 TC 43 Z9 46 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2012 VL 37 IS 3 BP 734 EP 745 DI 10.1038/npp.2011.250 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 876OV UT WOS:000299117900015 PM 22030709 ER PT J AU Garnick, MB AF Garnick, Marc B. TI THE GREAT PROSTATE CANCER DEBATE SO SCIENTIFIC AMERICAN LA English DT Article C1 [Garnick, Marc B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Garnick, Marc B.] Bostons Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Garnick, MB (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0036-8733 J9 SCI AM JI Sci.Am. PD FEB PY 2012 VL 306 IS 2 BP 38 EP 43 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 880GZ UT WOS:000299394600016 PM 22295676 ER PT J AU Janeway, KA Weldon, CB AF Janeway, Katherine A. Weldon, Christopher B. TI Pediatric gastrointestinal stromal tumor SO SEMINARS IN PEDIATRIC SURGERY LA English DT Article DE Gastrointestinal stromal tumor; GIST; Pediatric; Review ID FINE-NEEDLE-ASPIRATION; OF-THE-LITERATURE; TYROSINE KINASE INHIBITORS; GUIDED TRUCUT BIOPSY; TERM-FOLLOW-UP; ENDOSCOPIC ULTRASOUND; IMATINIB MESYLATE; SURGICAL-MANAGEMENT; CELL TUMORS; PROGNOSTIC-FACTORS AB Pediatric gastrointestinal stromal tumor (GIST) is a rare entity that can be quite different from its adult counterpart. This report provides a comprehensive review on the diagnosis and management of this tumor in children and adolescents, including its oncogenesis and associated syndromes. Surgery remains a mainstay of treatment, but there are no standard guidelines available at this time regarding the best practice for multimodality therapy as our understanding of the biology of GIST is still in evolution. Therefore, pediatric patients with GIST should be ideally treated in the context of clinical trials at specialized, multidisciplinary centers throughout the course of their disease, especially because these patients may live for years after diagnosis. (C) 2012 Elsevier Inc. All rights reserved. C1 [Weldon, Christopher B.] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Janeway, Katherine A.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Weldon, CB (reprint author), Childrens Hosp, Dept Surg, 300 Longwood Ave,Fegan 3, Boston, MA 02115 USA. EM christopher.weldon@childrens.harvard.edu NR 107 TC 10 Z9 10 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1055-8586 EI 1532-9453 J9 SEMIN PEDIATR SURG JI Semin. Pediatr. Surg. PD FEB PY 2012 VL 21 IS 1 BP 31 EP 43 DI 10.1053/j.sempedsurg.2011.10.003 PG 13 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 878GH UT WOS:000299243000005 PM 22248968 ER PT J AU Langdale, LA AF Langdale, Lorrie A. TI WHAT'S NEW IN SHOCK, FEBRUARY 2012? SO SHOCK LA English DT Editorial Material C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Langdale, LA (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 16 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD FEB PY 2012 VL 37 IS 2 BP 127 EP 130 DI 10.1097/SHK.0b013e31824255b3 PG 4 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 879FS UT WOS:000299315700001 PM 22249217 ER PT J AU Kitchens, WH Yeh, HD Van Cott, EM Elias, N Kawai, T Markmann, JF Hertl, M AF Kitchens, William H. Yeh, Heidi Van Cott, Elizabeth M. Elias, Nahel Kawai, Tatsuo Markmann, James F. Hertl, Martin TI Protein S deficiency in a living liver donor SO TRANSPLANT INTERNATIONAL LA English DT Article DE coagulation disorders; living donor evaluation; living donor liver transplantation; protein S deficiency; thrombophilia ID VENOUS THROMBOSIS; INHERITED THROMBOPHILIA; FAMILY COHORT; TRANSPLANTATION; RISK; PREVALENCE; GENE AB Protein S deficiency is a thrombophilia associated with increased risk of thromboembolic episodes in affected patients. Traditionally, protein S deficiency in a potential donor was considered an absolute contraindication to living donor liver transplantation, both due to the increased risk incurred by the thrombophilic donor as well as the risk of transmitting the thrombophilia to the liver recipient, as protein S is predominantly produced by the liver. We present the first successful case of living donor liver transplantation using a donor with asymptomatic protein S deficiency. Interestingly, whereas the donor continued to have protein S levels approximately 50% of normal, the recipient maintained normal levels of protein S post-transplant, potentially due to compensation by extra-hepatic protein S production. We discuss the prior literature of protein S deficiency acquired via liver transplantation, and we evaluate potential criteria by which the safety of transplants utilizing this pool of donors may be enhanced. C1 [Yeh, Heidi; Elias, Nahel; Kawai, Tatsuo; Markmann, James F.; Hertl, Martin] Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Hertl, M (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, White Bldg 546C,55 Fruit St, Boston, MA 02114 USA. EM mhertl@partners.org NR 21 TC 0 Z9 0 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0934-0874 J9 TRANSPL INT JI Transpl. Int. PD FEB PY 2012 VL 25 IS 2 BP E23 EP E26 DI 10.1111/j.1432-2277.2011.01404.x PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA 876JM UT WOS:000299103800001 PM 22175543 ER PT J AU Biederman, J Petty, CR O'Connor, KB Hyder, LL Faraone, SV AF Biederman, J. Petty, C. R. O'Connor, K. B. Hyder, L. L. Faraone, S. V. TI Predictors of persistence in girls with attention deficit hyperactivity disorder: results from an 11-year controlled follow-up study SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE attention deficit hyperactivity disorder; persistence; predictors; longitudinal; young adult ID AGE-DEPENDENT DECLINE; MAJOR LIFE ACTIVITIES; DEFICIT/HYPERACTIVITY DISORDER; CONDUCT PROBLEMS; GENDER-DIFFERENCES; PSYCHIATRIC STATUS; ANXIETY DISORDERS; EARLY ADOLESCENCE; CHILDREN; ADHD AB Objective: This study sought to examine the age-dependent persistence of attention deficit hyperactivity disorder (ADHD) and its predictors in a large sample of girls with and without ADHD followed prospectively for 11 years into young adulthood. Method: Participants were girls with (N = 96) and without (N = 91) ADHD and were 6-17 years old at the baseline assessment (mean age, 11 years) and 15-30 years old at the follow-up assessment (mean: 22 years). Participants were comprehensively and blindly assessed with structured diagnostic interviews and assessments of cognitive, social, school, and family functioning. Results: At the 11-year follow-up, 33.3% met full criteria for ADHD, 29.2% showed partial persistence of the disorder, 10.4% had impaired functioning, and 4.2% were remitted but treated (77.1% of the sample). Predictors of persistence were psychiatric comorbidity, family history of psychopathology, and family and school functioning at baseline. Conclusion: These long-term, prospective, follow-up findings extend to girls findings that ADHD is persistent over the long term and can be predicted from psychosocial adversity and psychiatric comorbidity ascertained 11 years earlier. C1 [Biederman, J.; Petty, C. R.; O'Connor, K. B.; Hyder, L. L.] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. [Biederman, J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Faraone, S. V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, S. V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 55 Fruit St,YAW 6A-6900, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Eli Lilly and Company Foundation; Pediatric Psychopharmacology Philanthropy Fund. FX This work was supported, in part by a grant from the Eli Lilly and Company Foundation and the Pediatric Psychopharmacology Philanthropy Fund. NR 48 TC 33 Z9 33 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD FEB PY 2012 VL 125 IS 2 BP 147 EP 156 DI 10.1111/j.1600-0447.2011.01797.x PG 10 WC Psychiatry SC Psychiatry GA 874GZ UT WOS:000298944700006 PM 22097933 ER PT J AU Dennerlein, JT Hopcia, K Sembajwe, G Kenwood, C Stoddard, AM Tveito, TH Hashimoto, DM Sorensen, G AF Dennerlein, Jack T. Hopcia, Karen Sembajwe, Grace Kenwood, Christopher Stoddard, Anne M. Tveito, T. Helene Hashimoto, Dean M. Sorensen, Glorian TI Ergonomic practices within patient care units are associated with musculoskeletal pain and limitations SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE musculoskeletal symptoms; health care; ergonomics; low back pain; organizational policy and practice ID DISABILITY MANAGEMENT-PRACTICES; LOW-BACK-PAIN; WORK DISABILITY; SYMPTOMS; WORKPLACES; NURSES; QUESTIONNAIRE; INTERVENTION; RELIABILITY; PREVENTION AB Background With the high prevalence of musculoskeletal disorders (MSDs) for patient care unit workers, prevention efforts through ergonomic practices within units may be related to symptoms associated with typical work-related MSDs. Methods We completed a cross-sectional survey of patient care workers (n = 1,572) in two large academic hospitals in order to evaluate relationships between self-reported musculoskeletal pain, work interference due to this pain, and limitations during activities of daily living (functional limitations) and with ergonomic practices and other organizational policy and practices metrics within the unit. Bivariate and multiple logistic regression analyses tested the significance of these associations. Results Prevalence of self-reported musculoskeletal symptoms in the past 3 months was 74% with 53% reporting pain in the low back. 32.8% reported that this pain interfered with their work duties and 17.7% reported functional limitations in the prior week. Decreased ergonomic practices were significantly associated with reporting pain in four body areas (low back, neck/shoulder, arms, and lower extremity) in the previous 3 months, interference with work caused by this pain, symptom severity, and limitations in completing activities of daily living in the past week. Except for low back pain and work interference, these associations remained significant when psychosocial covariates such as psychological demands were included in multiple logistic regressions. Conclusions Ergonomic practices appear to be associated with many of the musculoskeletal symptoms denoting their importance for prevention efforts in acute health care settings. Am. J. Ind. Med. 55: 107-116, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Dennerlein, Jack T.; Sembajwe, Grace; Tveito, T. Helene] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Dennerlein, Jack T.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Hopcia, Karen; Sembajwe, Grace; Hashimoto, Dean M.] Partners HealthCare Inc, Dept Occupat Hlth, Boston, MA USA. [Kenwood, Christopher; Stoddard, Anne M.] New England Res Inst, Watertown, MA 02172 USA. [Tveito, T. Helene] Univ Bergen, Bergen, Norway. [Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Sorensen, Glorian] Dana Faber Canc Inst, Ctr Community Based Res, Boston, MA USA. RP Dennerlein, JT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM jax@hsph.harvard.edu OI Dennerlein, Jack/0000-0001-7703-643X FU National Institute for Occupational Safety and Health [U19 OH008861] FX Contract grant sponsor: National Institute for Occupational Safety and Health; Contract grant number: U19 OH008861. Disclosure Statement: The authors report no conflicts of interests. NR 36 TC 16 Z9 17 U1 3 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD FEB PY 2012 VL 55 IS 2 BP 107 EP 116 DI 10.1002/ajim.21036 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 871JL UT WOS:000298734000002 PM 22113975 ER PT J AU Boden, LI Sembajwe, G Tveito, TH Hashimoto, D Hopcia, K Kenwood, C Stoddard, AM Sorensen, G AF Boden, Leslie I. Sembajwe, Grace Tveito, Torill H. Hashimoto, Dean Hopcia, Karen Kenwood, Christopher Stoddard, Anne M. Sorensen, Glorian TI Occupational injuries among nurses and aides in a hospital setting SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE occupational injuries; OSHA-recordable injuries; hospital injury rates; healthcare workers ID HEALTH-CARE WORKERS; NURSING PERSONNEL; BACK INJURIES; RISK-FACTORS; COMPENSATION; WORKPLACE; ILLNESS; SURVEILLANCE; DISORDERS; RATES AB Background Patient care workers in acute care hospitals are at high risk of injury. Recent studies have quantified risks and demonstrated a higher risk for aides than for nurses. However, no detailed studies to date have used OSHA injury definitions to allow for better comparability across studies. Methods We linked records from human resources and occupational health services databases at two large academic hospitals for nurses (n = 5,991) and aides (n 1,543) in patient care units. Crude rates, rate ratios, and confidence intervals were calculated for injuries involving no days away and those involving at least 1 day away from work. Results Aides have substantially higher injury rates per 100 full-time equivalent workers (FTEs) than nurses for both injuries involving days away from work (11.3 vs. 7.2) and those involving no days away (9.9 vs. 5.7). Back injuries were the most common days away (DA) injuries, while sharps injuries were the most common no days away (NDA) injuries. Pediatric/neonatal units and non-inpatient units had the lowest injury rates. Operating rooms and the float pool had high DA injury rates for both occupations, and stepdown units had high rates for nurses. NDA injuries were highest in the operating room for both nurses and aides. Conclusions This study supports the importance of a continuing emphasis on preventing back and sharps injuries and reducing risks faced by aides in the hospital setting. Uniform injury definitions and work time measures can help benchmark safety performance and focus prevention efforts. Am. J. Ind. Med. 55: 117-126, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Boden, Leslie I.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02118 USA. [Sembajwe, Grace; Tveito, Torill H.; Hashimoto, Dean] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Tveito, Torill H.] Univ Bergen, Bergen, Norway. [Hashimoto, Dean; Hopcia, Karen; Sorensen, Glorian] Partners HealthCare Syst, Occupat Hlth Serv, Boston, MA USA. [Hashimoto, Dean; Hopcia, Karen; Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Kenwood, Christopher; Stoddard, Anne M.] New England Res Inst, Watertown, MA 02172 USA. [Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Boden, LI (reprint author), Boston Univ, Sch Publ Hlth, Dept Environm Hlth, 715 Albany St, Boston, MA 02118 USA. EM lboden@bu.edu OI Boden, Leslie/0000-0002-9779-207X FU National Institute for Occupational Safety and Health [5U19 OH008861] FX Contract grant sponsor: National Institute for Occupational Safety and Health; Contract grant number: 5U19 OH008861. NR 32 TC 15 Z9 15 U1 2 U2 24 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD FEB PY 2012 VL 55 IS 2 BP 117 EP 126 DI 10.1002/ajim.21018 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 871JL UT WOS:000298734000003 PM 22025077 ER PT J AU Clements, PJ Tan, M McLaughlin, VV Oudiz, RJ Tapson, VF Channick, RN Rubin, LJ Langer, A AF Clements, Philip J. Tan, Mary McLaughlin, Vallerie V. Oudiz, Ronald J. Tapson, Victor F. Channick, Richard N. Rubin, Lewis J. Langer, Anatoly CA Pulm Arterial Hypertension Quality TI The pulmonary arterial hypertension quality enhancement research initiative: comparison of patients with idiopathic PAH to patients with systemic sclerosis-associated PAH SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID SURVIVAL; REGISTRY; GUIDELINES; DIAGNOSIS; REVEAL; ERA AB Objective The objective of this report is to compare baseline, management and survival characteristics in idiopathic pulmonary arterial hypertension (IPAH) with systemic sclerosis-associated pulmonary arterial hypertension (SSc-APAH) using data from the prospectively enrolled PAH Quality Enhancement Research Initiative. Methods Between August 2005 and July 2007, patients with IPAH and SSc-APAH were enrolled across 60 US sites and followed up for 3 years. Data on diagnostic tests, clinical variables, pulmonary arterial hypertension (PAH) medication and outcomes were recorded. Results With some exceptions, baseline clinical and laboratory characteristics were similar between the 279 patients with IPAH and the 228 with SSc-APAH. Patients with SSc-APAH were older at the time of PAH diagnosis, were more likely to be female and were antinuclear antibody positive. Patients with SSc-APAH had poorer spirometric results. During the 3-year follow-up, both groups were managed with prostacyclin and prostacyclin analogue treatment, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors (PDE5i) singly or in combination. At 3 years, patients with SSc-APAH were more likely to be treated with PDE5i alone or with an endothelin receptor antagonist. Patients with SSc-APAH had a significantly lower survival rate compared to patients with IPAH (60% vs 77%, p<0.0001). Conclusions The cohort with SSc-APAH was older, was more severely ill, was more likely to be female, was managed with PDE5i and had reduced 3-year survival compared with the cohort with IPAH. C1 [Clements, Philip J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Tan, Mary; Langer, Anatoly] Canadian Heart Res Ctr, Toronto, ON, Canada. [McLaughlin, Vallerie V.] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA. [Oudiz, Ronald J.] Harbor UCLA Med Ctr, Dept Med, Biomed Res Inst, Los Angeles, CA USA. [Tapson, Victor F.] Duke Univ, Med Ctr, Dept Med, Durham, NC USA. [Channick, Richard N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rubin, Lewis J.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. RP Clements, PJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 1000 Veteran Ave, Los Angeles, CA 90095 USA. EM pclements@mednet.ucla.edu FU Gilead Sciences; Actelion Pharmaceuticals US; Bayer; United Therapeutics; Novartis Pharmaceuticals; LungRx; Pfizer; Arena FX PJC has received consulting fees from Gilead Sciences. MT has no competing interests. VVMcL has received consulting/speaking fees from Actelion Pharmaceuticals US, Bayer, Gilead Sciences and United Therapeutics. VVMcL has received research grants from Actelion Pharmaceuticals US, Gilead Sciences, Novartis Pharmaceuticals and United Therapeutics. RJO has received consulting fees and research grants from Actelion Pharmaceuticals US, Bayer, Gilead Sciences, LungRx, Pfizer and United Therapeutics. VFT has received research grants from Arena, Bayer, Gilead Sciences, LungRx and United Therapeutics. RNC has received consulting fees from Actelion Pharmaceuticals US and received research grants from Gilead Sciences. LJR has received research grants from Actelion Pharmaceuticals US, Gilead Sciences, Pfizer and United Therapeutics. AL has received research grants from Actelion Pharmaceuticals US. NR 18 TC 23 Z9 25 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 FEB PY 2012 VL 71 IS 2 BP 249 EP 252 DI 10.1136/annrheumdis-2011-200265 PG 4 WC Rheumatology SC Rheumatology GA 870PQ UT WOS:000298681800016 PM 21998119 ER PT J AU Makimura, H Feldpausch, MN Stanley, TL Sun, N Grinspoon, SK AF Makimura, Hideo Feldpausch, Meghan N. Stanley, Takara L. Sun, Noelle Grinspoon, Steven K. TI Reduced growth hormone secretion in obesity is associated with smaller LDL and HDL particle size SO CLINICAL ENDOCRINOLOGY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; LECITHIN-CHOLESTEROL ACYLTRANSFERASE; TRANSFER PROTEIN ACTIVITIES; CORONARY-ARTERY DISEASE; ESTER TRANSFER PROTEIN; INSULIN-RESISTANCE; LIPOPROTEIN SUBCLASSES; REPLACEMENT THERAPY; MEN; DEFICIENT AB Objective Reduced growth hormone (GH) secretion is observed in obesity and may contribute to increases in cardiovascular disease (CVD) risk. Lipoprotein characteristics including increased small dense low-density lipoprotein (LDL) particles are known independent risk factors for CVD. We hypothesized that reduced GH secretion in obesity would be associated with a more atherogenic lipid profile including increased small dense LDL particles. C1 [Makimura, Hideo; Feldpausch, Meghan N.; Stanley, Takara L.; Sun, Noelle; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Makimura, Hideo; Feldpausch, Meghan N.; Stanley, Takara L.; Sun, Noelle; Grinspoon, Steven K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Stanley, Takara L.] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Makimura, Hideo] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Makimura, H (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 211, Boston, MA 02114 USA. EM hmakimura@partners.org FU National Institutes of Health [R01HL085268, K24DK064545, K23DK087857, K23DK089910, M01RR01066, UL1RR025758]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources FX We gratefully acknowledge the MGH bionutrition and nursing staffs and the research volunteers for their participation in the study. In addition, we would like to acknowledge the following funding sources for their financial support: National Institutes of Health grant R01HL085268 to SKG, K24DK064545 to SKG, K23DK087857 to HM, K23DK089910 to TLS and M01RR01066 and UL1RR025758, Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. This study was registered at http://www.clinicaltrials.gov as NCT00562796. NR 27 TC 11 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD FEB PY 2012 VL 76 IS 2 BP 220 EP 227 DI 10.1111/j.1365-2265.2011.04195.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 872ED UT WOS:000298790600011 PM 21819438 ER PT J AU Kinlay, S AF Kinlay, Scott TI Role of C-Reactive Protein When Prescribing a Statin SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE C-reactive protein; CRP; LDL cholesterol; Screening; High-risk strategy; Variability; Prediction ID CORONARY-HEART-DISEASE; RISK-FACTORS; CARDIOVASCULAR-DISEASE; HEALTHY-ADULTS; ATHEROSCLEROSIS; JUPITER; EVENTS; ATORVASTATIN; INFLAMMATION; METAANALYSIS AB The clinical value of measuring C-reactive protein (CRP) to guide statin therapy is uncertain. It has no value in patients at high risk who would be treated regardless of CRP (eg, patients with coronary disease or of equivalent risk), in patients at low risk who do not warrant treatment, and those with other acute or chronic inflammatory conditions that amplify CRP. Drawbacks to the widespread clinical use of CRP include its small impact on risk prediction beyond other risk factors, and evidence from JUPITER and other trials that baseline CRP is unable to identify patients who obtain greater absolute benefits from statin therapy. Furthermore, the within-person variability of CRP is about the same as the reduction in CRP from intensive statin therapy, and this leads to many patients registering an increase in CRP with treatment. For these reasons, CRP has no clear role in determining who should receive statin therapy or for monitoring the success of treatment. C1 [Kinlay, Scott] VA Boston Healthcare Syst, Div Cardiovasc, W Roxbury, MA 02132 USA. [Kinlay, Scott] Harvard Univ, Sch Med, Boston, MA USA. [Kinlay, Scott] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Div Cardiovasc, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM scott.kinlay@va.gov NR 40 TC 1 Z9 2 U1 0 U2 0 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 FEB PY 2012 VL 14 IS 1 BP 26 EP 32 DI 10.1007/s11883-011-0218-8 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 874YW UT WOS:000298995900004 PM 22125118 ER PT J AU Schwartz, GG AF Schwartz, Gregory G. TI New Horizons for Cholesterol Ester Transfer Protein Inhibitors SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE Cholesterol ester transfer protein; High density lipoprotein; Torcetrapib; Anacetrapib; Dalcetrapib ID DENSITY-LIPOPROTEIN CHOLESTEROL; TYPE-2 DIABETES-MELLITUS; RANDOMIZED CONTROLLED-TRIAL; LIPID-LEVEL MANAGEMENT; CORONARY-HEART-DISEASE; CETP INHIBITOR; ENDOTHELIAL FUNCTION; HEALTHY-SUBJECTS; HDL CHOLESTEROL; CLINICAL-TRIAL AB High-density lipoprotein (HDL) cholesterol levels bear an inverse relationship to cardiovascular risk. To date, however, no intervention specifically targeting HDL has been demonstrated to reduce cardiovascular risk. Cholesterol ester transfer protein (CETP) mediates transfer of cholesterol ester from HDL to apolipoprotein B-containing particles. Most, but not all observational cohort studies indicate that genetic polymorphisms of CETP associated with reduced activity and higher HDL cholesterol levels are also associated with reduced cardiovascular risk. Some, but not all studies indicate that CETP inhibition in rabbits retards atherosclerosis, whereas transgenic CETP expression in mice promotes atherosclerosis. Torcetrapib, the first CETP inhibitor to reach phase III clinical development, was abandoned due to excess mortality associated with increases in aldosterone and blood pressure. Two other CETP inhibitors have entered phase III clinical development. Anacetrapib is a potent inhibitor of CETP that produces very large increases in HDL cholesterol and large reductions in low-density lipoprotein (LDL) cholesterol, beyond those achieved with statins. Dalcetrapib is a less potent CETP inhibitor that produces smaller increases in HDL cholesterol with minimal effect on LDL cholesterol. Both agents appear to allow efflux of cholesterol from macrophages to HDL in vitro, and neither agent affects blood pressure or aldosterone in vivo. Two large cardiovascular outcomes trials, one with anacetrapib and one with dalcetrapib, should provide a conclusive test of the hypothesis that inhibition of CETP decreases cardiovascular risk. C1 [Schwartz, Gregory G.] Denver VA Med Ctr, Denver, CO 80220 USA. [Schwartz, Gregory G.] Univ Colorado, Denver, CO 80202 USA. [Schwartz, Gregory G.] VA Med Ctr, Denver, CO USA. RP Schwartz, GG (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM Gregory.Schwartz@va.gov FU Roche Laboratories FX G.G. Schwartz has received research grants from Roche Laboratories. NR 45 TC 11 Z9 11 U1 0 U2 1 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 FEB PY 2012 VL 14 IS 1 BP 41 EP 48 DI 10.1007/s11883-011-0217-9 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 874YW UT WOS:000298995900006 PM 22083134 ER PT J AU Wei, NJ Wexler, DJ AF Wei, Nancy J. Wexler, Deborah J. TI Basal-Bolus Insulin Protocols Enter the Computer Age SO CURRENT DIABETES REPORTS LA English DT Article DE Basal-bolus insulin protocols; Inpatient glycemic management; Computerized order entry; Electronic decision support; Standardized insulin order sets; Hyperglycemia ID CRITICALLY-ILL PATIENTS; ASSOCIATION CONSENSUS STATEMENT; QUALITY IMPROVEMENT EFFORTS; INPATIENT GLYCEMIC CONTROL; ORDER SET; CLINICAL ENDOCRINOLOGISTS; AMERICAN ASSOCIATION; GLUCOSE CONTROL; HEMOGLOBIN A1C; HYPERGLYCEMIA AB Diabetes affects approximately one quarter of all hospitalized patients. Poor inpatient glycemic control has been associated with increased risk for multiple adverse events including surgical site infections, prolonged hospital length of stay, and mortality. Inpatient glycemic control protocols based on physiologic basal-bolus insulin regimens have been shown to improve glycemia and clinical outcomes and are recommended by the American Diabetes Association, the American Association of Clinical Endocrinologists, and the Society of Hospital Medicine for inpatient glycemic management of noncritically ill patients. The 2009 Health Information Technology for Economic and Clinical Health (HITECH) Act will catalyze widespread computerized medication order entry implementation over the next few years. Here, we focus on the noncritical care setting and review the background on inpatient glycemic management as it pertains to computerized order entry, the translation and efficacy of computerizing glycemic control protocols, and the barriers to computerizing glycemic protocols. C1 [Wei, Nancy J.; Wexler, Deborah J.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Wei, Nancy J.; Wexler, Deborah J.] Harvard Univ, Sch Med, Boston, MA USA. RP Wei, NJ (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 55 Fruit St, Boston, MA 02114 USA. EM ncwei@partners.org FU NIDDK [T32 DK007028-36, K23 DK 080 228] FX N.J. Wei is supported by an NIDDK training grant (T32 DK007028-36). D.J. Wexler is supported by an NIDDK Career Development Award (K23 DK 080 228). NR 48 TC 9 Z9 9 U1 1 U2 1 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD FEB PY 2012 VL 12 IS 1 BP 119 EP 126 DI 10.1007/s11892-011-0240-9 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 874AD UT WOS:000298926500016 PM 22015856 ER PT J AU Levitsky, LL AF Levitsky, Lynne L. TI Growth and development potpourri SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Pediat Endocrine Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Levitsky, LL (reprint author), Harvard Univ, Sch Med, Pediat Endocrine Unit, Massachusetts Gen Hosp, 175 Cambridge St 5th Floor, Boston, MA 02114 USA. EM LLevitsky@partners.org 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 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2012 VL 19 IS 1 BP 26 EP 27 DI 10.1097/MED.0b013e32834f0b70 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 866RV UT WOS:000298400600006 PM 22157407 ER PT J AU Stanley, T AF Stanley, Takara TI Diagnosis of growth hormone deficiency in childhood SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Review DE growth hormone; growth hormone deficiency; IGFBP-3; IGF-I ID FACTOR-BINDING PROTEIN-3; ISOLATED GH DEFICIENCY; SHORT STATURE; IGF-I; SERUM-LEVELS; PROMOTER POLYMORPHISM; PROVOCATIVE TESTS; SHORT CHILDREN; YOUNG-ADULTS; INSULIN AB Purpose of review The diagnosis of growth hormone deficiency (GHD) in childhood is challenging, in large part because of the lack of a true gold standard and the relatively poor performance of available diagnostic testing. This review discusses the recent literature on this topic. Recent findings Auxology and clinical judgment remain the foundation for the diagnosis of GHD. Provocative growth hormone testing is poorly reproducible, dependent on factors such as body composition and pubertal status, and further limited by significant variability among commercially available growth hormone assays. Measurement of insulin-like growth factor I and insulin-like growth factor-binding protein 3 is not diagnostically useful in isolation but is helpful in combination with other diagnostic measures. Neuroimaging is also useful to inform diagnosis, as pituitary abnormalities suggest a higher likelihood of GHD persisting into adulthood. Although genetic testing is not routinely performed in the diagnosis of GHD at the present time, multiple recent reports raise the possibility that it may play a more important role in diagnosing GHD in the future. Summary Beyond physicians' integrated assessment of auxology, clinical presentation, and bone age, current tools to diagnose GHD are suboptimal. Recent literature emphasizes the need to reappraise our current practice and to consider new tools for diagnosis. C1 [Stanley, Takara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab,Pediat Endocrine Unit, Boston, MA USA. RP Stanley, T (reprint author), LON5-207,55 Fruit St, Boston, MA 02114 USA. EM tstanley@partners.org FU National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases) [1K23DK089910] FX The author was supported by National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases) grant 1K23DK089910. NR 47 TC 19 Z9 22 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2012 VL 19 IS 1 BP 47 EP 52 DI 10.1097/MED.0b013e32834ec952 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 866RV UT WOS:000298400600010 PM 22157400 ER PT J AU Walford, GA Green, T Neale, B Isakova, T Rotter, JI Grant, SFA Fox, CS Pankow, JS Wilson, JG Meigs, JB Siscovick, DS Bowden, DW Daly, MJ Florez, JC AF Walford, G. A. Green, T. Neale, B. Isakova, T. Rotter, J. I. Grant, S. F. A. Fox, C. S. Pankow, J. S. Wilson, J. G. Meigs, J. B. Siscovick, D. S. Bowden, D. W. Daly, M. J. Florez, J. C. TI Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism SO DIABETOLOGIA LA English DT Article DE Common genetic variants; Diabetes mellitus; Genetics; Glycaemic progression; Impaired fasting glucose; Normal fasting glucose; Single nucleotide polymorphism; Type 2 diabetes ID TYPE-2 DIABETES RISK; FOLLOW-UP; ASSOCIATION ANALYSIS; TRIGLYCERIDE LEVELS; INSULIN-SECRETION; PLASMA-GLUCOSE; MTNR1B; LOCI; MELLITUS; DESIGN AB Common genetic variants have been associated with type 2 diabetes. We hypothesised that a subset of these variants may have different effects on the transition from normal fasting glucose (NFG) to impaired fasting glucose (IFG) than on that from IFG to diabetes. We identified 16 type 2 diabetes risk variants from the Illumina Broad Candidate-gene Association Resource (CARe) array genotyped in 26,576 CARe participants. Participants were categorised at baseline as NFG, IFG or type 2 diabetic (n = 16,465, 8,017 or 2,291, respectively). Using Cox proportional hazards and likelihood ratio tests (LRTs), we compared rates of progression by genotype for 4,909 (NFG to IFG) and 1,518 (IFG to type 2 diabetes) individuals, respectively. We then performed multinomial regression analyses at baseline, comparing the risk of assignment to the NFG, IFG or diabetes groups by genotype. The rate of progression from NFG to IFG was significantly greater in participants carrying the risk allele at MTNR1B (p = 1 x 10(-4)), nominally greater at GCK and SLC30A8 (p < 0.05) and nominally smaller at IGF2BP2 (p = 0.01) than the rate of progression from IFG to diabetes by the LRT. Results of the baseline, multinomial regression model were consistent with these findings. Common genetic risk variants at GCK, SLC30A8, IGF2BP2 and MTNR1B influence to different extents the development of IFG and the transition from IFG to type 2 diabetes. Our findings may have implications for understanding the genetic contribution of these variants to the development of IFG and type 2 diabetes. C1 [Walford, G. A.; Green, T.; Neale, B.; Daly, M. J.; Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Walford, G. A.; Florez, J. C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Walford, G. A.; Green, T.; Neale, B.; Daly, M. J.; Florez, J. C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Walford, G. A.; Isakova, T.; Florez, J. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Isakova, T.] Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. [Grant, S. F. A.] Childrens Hosp Philadelphia, Res Inst, Div Human Genet, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Grant, S. F. A.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Siscovick, D. S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Siscovick, D. S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Wilson, J. G.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Wilson, J. G.] VA Med Ctr, Dept Med, Jackson, MS USA. [Fox, C. S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Fox, C. S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Meigs, J. B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, J. B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Pankow, J. S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Bowden, D. W.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Ctr Human Genom, Winston Salem, NC 27103 USA. [Bowden, D. W.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Ctr Diabet Res, Winston Salem, NC 27103 USA. [Rotter, J. I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Simches Res Bldg CPZN 5-250,185 Cambridge St, Boston, MA 02114 USA. EM jcflorez@partners.org OI Pankow, James/0000-0001-7076-483X FU NIH [DK007028]; Scholars in Clinical Science programme of Harvard Catalyst-The Harvard Clinical and Translational Science Center [UL1 RR 025758]; Harvard University; NIDDK [K24 DK080140]; Doris Duke Charitable Foundation; National Heart, Lung, and Blood Institute FX G.A. Walford (Massachusetts General Hospital) received support from NIH training grant DK007028 and from the Scholars in Clinical Science programme of Harvard Catalyst-The Harvard Clinical and Translational Science Center (award UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic healthcare centres). J.B. Meigs (Massachusetts General Hospital) is supported in part by NIDDK K24 DK080140. J.C. Florez (Massachusetts General Hospital) is supported by a Clinical Scientist Development Award from the Doris Duke Charitable Foundation. The 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 involved in creating this resource for biomedical research. Specific funding information for the nine parent studies contributing to CARe can be found in the ESM text. This study was presented in poster form as a late-breaking abstract at the 2010 American Diabetes Association Scientific Sessions in Orlando, FL, USA. NR 34 TC 13 Z9 14 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2012 VL 55 IS 2 BP 331 EP 339 DI 10.1007/s00125-011-2353-8 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 866OZ UT WOS:000298392000008 PM 22038522 ER PT J AU Shyn, PB Oliva, MR Shah, SH Tatli, S Catalano, PJ Silverman, SG AF Shyn, Paul B. Oliva, M. Raquel Shah, Shaan H. Tatli, Servet Catalano, Paul J. Silverman, Stuart G. TI MRI contrast enhancement of malignant liver tumours following successful cryoablation SO EUROPEAN RADIOLOGY LA English DT Article DE Ablation techniques; Cryoablation; Liver Neoplasms; Magnetic Resonance Imaging; Contrast Media ID EXPERIENCE; INJURY AB Objectives To assess the incidence and degree of MRI contrast enhancement in liver tumours following successful percutaneous cryoablation. Methods Thirty-eight patients with liver metastases (n = 29) or hepatocellular carcinoma (n = 9) underwent percutaneous cryoablation of 45 tumours between March 2004 and June 2009, with complete ablation zone coverage of the tumour and no local recurrence on follow-up imaging to date (range 3-60 months, mean 16). Contrast-enhanced MRI was used to assess 45 tumours at 24 h, 32 tumours at 2-4 months, and 21 tumours at 5-7 months. Percentage of tumours with contrast enhancement was assessed using dynamic spoiled gradient echo T1-weighted images. Results Twenty-four hours post-cryoablation, 23 out of 45 tumours (51%) enhanced compared with 42 out of 43 (98%) pre-ablation (p < 0.001). Mean percentage tumour enhancement decreased from 157% (range 26-745%) pre-ablation, to 107% (27-260%) at 24 h (p = 0.003), and 43% (24-103%) at 2-4 months (p < 0.001). The incidence and degree of tumour enhancement decreased through 5-7 months. Conclusions Unlike previously reported studies of radiofrequency ablation, successful cryoablation of liver tumours is often associated with persistent tumour contrast enhancement on MRI performed at 24 h and decreasing over 2-7 months. Key Points Liver neoplasms often demonstrate MRI contrast enhancement following successful percutaneous cryoablation. This differs from radiofrequency ablation techniques where contrast enhancement suggests residual tumour This difference could potentially lead to important errors in follow up strategies. C1 [Shyn, Paul B.; Oliva, M. Raquel; Shah, Shaan H.; Tatli, Servet; Silverman, Stuart G.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Shyn, PB (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM pshyn@partners.org NR 13 TC 3 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD FEB PY 2012 VL 22 IS 2 BP 398 EP 403 DI 10.1007/s00330-011-2254-8 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 870ED UT WOS:000298651000017 PM 21898153 ER PT J AU Sonpavde, G Choueiri, TK Escudier, B Ficarra, V Hutson, TE Mulders, PF Patard, JJ Rini, BI Staehler, M Sternberg, CN Stief, CG AF Sonpavde, Guru Choueiri, Toni K. Escudier, Bernard Ficarra, Vincenzo Hutson, Thomas E. Mulders, Peter F. Patard, Jean-Jacques Rini, Brian I. Staehler, Michael Sternberg, Cora N. Stief, Christian G. TI Sequencing of Agents for Metastatic Renal Cell Carcinoma: Can We Customize Therapy? SO EUROPEAN UROLOGY LA English DT Review DE Renal cell carcinoma; Tyrosine kinase inhibitor; Second-line therapy; Axitinib; Everolimus ID PHASE-III TRIAL; GLOBAL EVALUATION TRIAL; INTERFERON-ALPHA; TARGETED THERAPY; RETROSPECTIVE ANALYSIS; SEQUENTIAL THERAPY; SUNITINIB; SORAFENIB; BEVACIZUMAB; EFFICACY AB Context: The expanding armamentarium of agents for the therapy of advanced clear cell renal cell carcinoma (RCC) warrants further investigation of optimal patient selection. Objective: To analyze the second and subsequent line of targeted therapies for advanced RCC while integrating clinical and molecular markers and imaging. Evidence acquisition: Data were acquired from research published in peer-reviewed literature or presented at major conferences. Evidence synthesis: Following first-line vascular endothelial growth factor (VEGF) inhibitors, second-line therapy with everolimus, a mammalian target of rapamycin inhibitor, and axitinib, a VEGF receptor tyrosine kinase inhibitor, have demonstrated benefits in progression-free survival (PFS). Sorafenib, pazopanib, and axitinib have demonstrated extension of PFS following cytokines. Optimal patient selection based on biomarkers is undergoing investigation. Clinical trials evaluating novel agents and combinations should be preferred. Conclusions: Currently, the sequence of therapy is based on patient and physician decision, which may be influenced by comorbidities and toxicity profiles. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved. C1 [Sonpavde, Guru] Texas Oncol, Houston, TX USA. [Sonpavde, Guru] Vet Affairs Med Ctr, Houston, TX 77030 USA. [Sonpavde, Guru] Baylor Coll Med, Houston, TX 77030 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Escudier, Bernard] Inst Gustave Roussy, Villejuif, France. [Ficarra, Vincenzo] Univ Padua, Padua, Italy. [Hutson, Thomas E.] Texas Oncol Baylor Sammons Canc Ctr, Dallas, TX USA. [Mulders, Peter F.] Univ Med Ctr Nijmegen, Nijmegen, Netherlands. [Patard, Jean-Jacques] Univ Paris 11, Bicetre Hosp, Le Kremlin Bicetre, France. [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Staehler, Michael] Univ Munich, Munich, Germany. [Sternberg, Cora N.] San Camillo Forlanini Hosp, Rome, Italy. RP Sonpavde, G (reprint author), Texas Oncol, 501 Med Ctr Blvd, Webster, TX 77598 USA. EM guru.sonpavde@usoncology.com RI Mulders, Peter/H-8076-2014 FU Novartis; Pfizer; Bayer/Onyx; GlaxoSmithKline FX I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Guru Sonpavde receives research support from Novartis and Pfizer, and is a speaker or on the advisory board for Novartis, Pfizer, and GSK. Toni K. Choueiri is on the advisory board of Pfizer, GSK, Aveo, Bayer/Onyx, Novartis, and Genentech. Bernard Escudier is a consultant for Pfizer, GSK, Aveo, Bayer, Novartis, and Roche. Vincenzo Ficarra is a speaker for Bayer and Pfizer. Thomas E. Hutson receives research support from Bayer/Onyx, Pfizer, and GlaxoSmithKline, and he is an advisory board/consultant for Bayer/Onyx and Pfizer and on the speaker's bureau for Bayer/Onyx, Pfizer, Amgen, Novartis, and Genentech. Jean-Jacques Patard is a consultant for Pfizer and GSK, and he receives research funding from Pfizer. Brian I. Rini is a consultant for Pfizer, Aveo, and GSK, and he receives research funding from Pfizer and GSK. Cora N. Sternberg is on the advisory board or a speaker for Pfizer, GSK, Novartis, and Aveo. Peter F. Mulders, Michael Staehler, and Christian G. Stief have nothing to disclose. NR 60 TC 31 Z9 33 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD FEB PY 2012 VL 61 IS 2 BP 307 EP 316 DI 10.1016/j.eururo.2011.10.032 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 864OE UT WOS:000298248700021 PM 22055147 ER PT J AU Jones, AM Beggs, AD Carvajal-Carmona, L Farrington, S Tenesa, A Walker, M Howarth, K Ballereau, S Hodgson, SV Zauber, A Bertagnolli, M Midgley, R Campbell, H Kerr, D Dunlop, MG Tomlinson, IPM AF Jones, A. M. Beggs, A. D. Carvajal-Carmona, L. Farrington, S. Tenesa, A. Walker, M. Howarth, K. Ballereau, S. Hodgson, S. V. Zauber, A. Bertagnolli, M. Midgley, R. Campbell, H. Kerr, D. Dunlop, M. G. Tomlinson, I. P. M. TI TERC polymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres SO GUT LA English DT Article ID GENOME-WIDE ASSOCIATION; DYSKERATOSIS-CONGENITA; GENETIC-VARIATION; HTERT EXPRESSION; LENGTH; RISK; MUTATIONS; CARCINOMA; APOPTOSIS; BIOLOGY AB Background and aims Shorter telomeres have been associated with increased risk of malignancy, including colorectal cancer (CRC). Telomere length is heritable and may be an intermediate phenotype linked to genetic susceptibility to CRC. Methods In a large sample, the study investigated whether candidate single nucleotide polymorphisms (SNP) in 'telomere biology' genes were associated with telomere length in leucocytes. SNP associated with an increased risk of CRC were searched for separately. Results Carriers of the common allele at SNP rs10936599, near the telomerase RNA component (TERC) locus, had significantly longer telomeres. It was independently found that the same rs10936599 allele was associated with increased risk of both CRC and colorectal adenomas. Neither telomere length nor CRC risk was associated with variation near telomerase reverse transcriptase or other telomere biology genes. In silico analysis showed that SNP rs2293607 was strongly correlated with rs10936599, mapped within TERC transcripts, had a predicted effect on messenger RNA folding and lay at a reported transcription factor binding site. TERC mRNA were expressed, differing only at the alleles of rs2293607, in CRC cell line HCT116. The long-telomere/CRC-risk allele was associated with higher levels of TERC mRNA and the formation of longer telomeres. Conclusions Common genetic variation at TERC is associated with both longer telomeres and an increased risk of CRC, a potential mechanism being reduced levels of cell senescence or death. This finding is somewhat paradoxical, given retrospective studies reporting that CRC cases have shorter telomeres than controls. One possibility is that that association actually results from poorer survival in patients with longer telomeres. C1 [Jones, A. M.; Beggs, A. D.; Carvajal-Carmona, L.; Howarth, K.; Tomlinson, I. P. M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Farrington, S.; Tenesa, A.; Walker, M.; Ballereau, S.; Dunlop, M. G.] Univ Edinburgh, Colon Canc Genet Grp, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Farrington, S.; Tenesa, A.; Walker, M.; Ballereau, S.; Dunlop, M. G.] MRC Human Genet Unit, Edinburgh, Midlothian, Scotland. [Hodgson, S. V.] St George Hosp, Sch Med, Dept Clin Genet, London, England. [Zauber, A.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Bertagnolli, M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Midgley, R.; Kerr, D.] Univ Oxford, Dept Clin Pharmacol, Oxford OX3 7BN, England. RP Tomlinson, IPM (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England. EM iant@well.ox.ac.uk RI Beggs, Andrew/F-5902-2010; Beggs, Andrew/A-6912-2013; Farrington, Susan/C-7319-2013; Dunlop, Malcolm/F-1973-2011; Carvajal-Carmona, Luis/B-3882-2010 OI Beggs, Andrew/0000-0003-0784-2967; Beggs, Andrew/0000-0003-0784-2967; Dunlop, Malcolm/0000-0002-3033-5851; Carvajal-Carmona, Luis/0000-0001-7129-2918 FU EU; Oxford Comprehensive Biomedical Research Centre; Cancer Research UK [C348/A12076]; Scottish Government Chief Scientist Office [K/OPR/2/2/D333]; Medical Research Council [G0000657-53203]; CORE as part of the Digestive Cancer Campaign; [090532/Z/09/Z] FX The Oxford group acknowledges funding from the EU FP7 CHIBCHA project, the Oxford Comprehensive Biomedical Research Centre and Cancer Research UK. The authors are also very grateful to Willem Ouwehand and colleagues for supplying the National Blood Service controls. The Edinburgh group were supported by grants from: Cancer Research UK (C348/A12076), Scottish Government Chief Scientist Office (K/OPR/2/2/D333), Medical Research Council (G0000657-53203) and a Centre Grant from CORE as part of the Digestive Cancer Campaign. Core infrastructure support to the Wellcome Trust Centre for Human Genetics, Oxford was provided by grant 090532/Z/09/Z. NR 41 TC 51 Z9 53 U1 0 U2 9 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD FEB PY 2012 VL 61 IS 2 BP 248 EP 254 DI 10.1136/gut.2011.239772 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 870JI UT WOS:000298665000012 PM 21708826 ER PT J AU Prentice, JC Fincke, BG Miller, DR Pizer, SD AF Prentice, Julia C. Fincke, B. Graeme Miller, Donald R. Pizer, Steven D. TI Primary Care and Health Outcomes among Older Patients with Diabetes SO HEALTH SERVICES RESEARCH LA English DT Article DE Access to care; mortality; primary care wait times; ambulatory-caresensitive conditions; diabetes ID INTENSIVE THERAPY; ADMINISTRATIVE DATA; COMPLICATIONS; ACCESS; COMORBIDITY; MORTALITY; QUALITY; VISITS; TRIAL AB Objective. The aim of this study was to measure the relationship between days spent waiting for primary care and health outcomes among patients diagnosed with diabetes, especially among the elderly population. Data Source. Secondary data from VA administrative databases and Medicare claims. Study Design. This is a retrospective observational study. Outcome variables include primary care utilization, mortality, heart attack, stroke, and ambulatory-care sensitive condition (ACSC) hospitalization. The main explanatory variable of interest is VA primary care wait time. Negative binomial models predict utilization and stacked logistic regression models predict the probability of experiencing each health outcome. Models are stratified by the presence of a selected health condition and age. Principal Findings. Longer wait times were predicted to decrease utilization between 2 and 4 percent. There was no significant relationship between wait times and health outcomes for the overall sample. In stratified analyses, longer waits were associated with undesirable outcomes for those over age 70 with one of the selected health conditions or in certain narrower 5-year age groups, but the overall pattern of results does not indicate a systematic and significant effect. Conclusions. There was a modest effect of long wait times on primary care utilization but no robust effect of longer wait times on health outcomes. Waiting for care did not significantly compromise long-term health outcomes for veterans with diabetes. C1 [Prentice, Julia C.] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA 02130 USA. [Fincke, B. Graeme; Miller, Donald R.; Pizer, Steven D.] Boston Univ, Sch Publ Hlth, Ctr Hlth Qual Outcomes & Econ Res, Edith Nourse Rogers Mem Hosp 152, Bedford, MA 02215 USA. [Pizer, Steven D.] Boston Univ, Dept Vet Affairs, Sch Publ Hlth Hlth Care Financing & Econ, VA Boston Healthcare Syst, Boston, MA 02215 USA. RP Prentice, JC (reprint author), Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, 150 S Huntington Ave,Mail Stop 152H, Boston, MA 02130 USA. EM julia.prentice@va.gov FU Health Services Research and Development Service, Department of Veterans Affairs [IAD-06-112, IIR 04-233]; Health Care Financing and Organization Initiative under the Robert Wood Johnson Foundation [62967] FX Funding for this research was provided by grant IAD-06-112 and IIR 04-233 from the Health Services Research and Development Service, Department of Veterans Affairs and grant 62967 from the Health Care Financing and Organization Initiative under the Robert Wood Johnson Foundation. The authors are indebted to Matthew Neuman and John Gardner, PhD, for programing support. The authors report no relationships or financial interests with any entity that would pose a conflict of interest. NR 41 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2012 VL 47 IS 1 BP 46 EP 67 DI 10.1111/j.1475-6773.2011.01307.x PN 1 PG 22 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 875OM UT WOS:000299040600005 PM 22092392 ER PT J AU Lichtenhan, JT AF Lichtenhan, Jeffery T. TI Effects of Low-Frequency Biasing on Otoacoustic and Neural Measures Suggest that Stimulus-Frequency Otoacoustic Emissions Originate Near the Peak Region of the Traveling Wave SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE amplitude modulation; low-frequency bias tone; cochlea; basilar membrane; auditory nerve; compound action potential; otoacoustic emissions ID GUINEA-PIG COCHLEA; TRANSDUCER OPERATING POINT; COHERENT REFLECTION; HAIR-CELLS; MECHANOELECTRICAL TRANSDUCTION; 2-TONE SUPPRESSION; BRAIN-STEM; MODEL; MODULATION; LATENCY AB Stimulus-frequency otoacoustic emissions (SFOAEs) have been used to study a variety of topics in cochlear mechanics, although a current topic of debate is where in the cochlea these emissions are generated. One hypothesis is that SFOAE generation is predominately near the peak region of the traveling wave. An opposing hypothesis is that SFOAE generation near the peak region is deemphasized compared to generation in the tail region of the traveling wave. A comparison was made between the effect of low-frequency biasing on both SFOAEs and a physiologic measure that arises from the peak region of the traveling wave-the compound action potential (CAP). SFOAE biasing was measured as the amplitude of spectral sidebands from varying bias tone levels. CAP biasing was measured as the suppression of CAP amplitude from varying bias tone levels. Measures of biasing effects were made throughout the cochlea. Results from cats show that the level of bias tone needed for maximum SFOAE sidebands and for 50% CAP reduction increased as probe frequency increased. Results from guinea pigs show an irregular bias effect as a function of probe frequency. In both species, there was a strong and positive relationship between the bias level needed for maximum SFOAE sidebands and for 50% CAP suppression. This relationship is consistent with the hypothesis that the majority of SFOAE is generated near the peak region of the traveling wave. C1 [Lichtenhan, Jeffery T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Lichtenhan, Jeffery T.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Lichtenhan, JT (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. EM jlichtenhan@gmail.com FU NIDCD, National Institutes of Health [F32 DC010112, RO1 DC00235, R01 DC03687, P30 DC005209] FX I thank John J. Guinan Jr. and Christopher A. Shera for their guidance through all stages of this project. For their valuable comments on the manuscript, I thank Maria A. Berezina, Nikolas A. Francis, Adam C. Furman, Ann E. Hickox, and three anonymous reviewers. This work was supported by grants F32 DC010112, RO1 DC00235, R01 DC03687, and P30 DC005209 from the NIDCD, National Institutes of Health. NR 48 TC 11 Z9 11 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD FEB PY 2012 VL 13 IS 1 BP 17 EP 28 DI 10.1007/s10162-011-0296-x PG 12 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 876FF UT WOS:000299092200002 PM 22002610 ER PT J AU Parmelee, PA Harralson, TL McPherron, JA DeCoster, J Schumacher, HR AF Parmelee, Patricia A. Harralson, Tina L. McPherron, Jesse A. DeCoster, Jamie Schumacher, H. Ralph TI Pain, Disability, and Depression in Osteoarthritis: Effects of Race and Sex SO JOURNAL OF AGING AND HEALTH LA English DT Article DE osteoarthritis; depression; disability; sex differences; ethnicity ID OLDER-ADULTS; KNEE OSTEOARTHRITIS; PHYSICAL-DISABILITY; RHEUMATOID-ARTHRITIS; ACTIVITY LIMITATIONS; ETHNIC-DIFFERENCES; RACIAL-DIFFERENCES; PRIMARY-CARE; WOMEN; SYMPTOMS AB Objectives: A cross-sectional study examined how race and sex affect associations among osteoarthritis (OA) pain, disability, and depression in 363 older adults with diagnosed knee OA. Method: African American (Black; N = 94) and non-Hispanic White (White; N = 269) men and women self-reported pain, disability, depressive symptoms, arthritis history, general health, and demographic information. Results: Women experienced greater pain and marginally greater disability than men; African Americans reported greater disability and marginally greater pain than non-Hispanic Whites. These effects varied with education, health, and arthritis history. In ordinary least squares regression analyses, race and pain independently predicted depression. Significant interactions of race, sex, and disability were driven by a lack of relationship between depression and disability among African American men. Discussion: Race and sex influence affective response to OA pain and disability in complex ways, with African American men showing paradoxical effects. Further research is needed to elucidate mechanisms of this moderation effect. C1 [Parmelee, Patricia A.] Univ Alabama, Ctr Mental Hlth & Aging, Tuscaloosa, AL 35487 USA. [Harralson, Tina L.] Polaris Hlth Direct, Langhorne, PA USA. [Schumacher, H. Ralph] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Parmelee, PA (reprint author), Univ Alabama, Ctr Mental Hlth & Aging, 207 Osband,Box 870315, Tuscaloosa, AL 35487 USA. EM pparmelee@ua.edu FU NIMH NIH HHS [1-R01-MH51800] NR 45 TC 15 Z9 15 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD FEB PY 2012 VL 24 IS 1 BP 168 EP 187 DI 10.1177/0898264311410425 PG 20 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 868YP UT WOS:000298562800008 PM 21693669 ER PT J AU Ono, N Nakashima, K Schipani, E Hayata, T Ezura, Y Soma, K Kronenberg, HM Noda, M AF Ono, Noriaki Nakashima, Kazuhisa Schipani, Ernestina Hayata, Tadayoshi Ezura, Yoichi Soma, Kunimichi Kronenberg, Henry M. Noda, Masaki TI Constitutively active PTH/PTHrP receptor specifically expressed in osteoblasts enhances bone formation induced by bone marrow ablation SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID STEM-CELL NICHE; PARATHYROID-HORMONE; IN-VIVO; DIFFERENTIATION; ARREST; SIZE AB Bone is maintained by continuous bone formation by osteoblasts provided by proliferation and differentiation of osteoprogenitors. Parathyroid hormone (PTH) activates bone formation, but because of the complexity of cells in the osteoblast lineage, how these osteoprogenitors are regulated by PTH in vivo is incompletely understood. To elucidate how signals by PTH in differentiated osteoblasts regulate osteoprogenitors in vivo, we conducted bone marrow ablation using Col1a1-constitutively active PTH/PTHrP receptor (caPPR) transgenic mice. These mice express caPPR specifically in osteoblasts by using 2.3kb Col1a1 promoter and showed higher trabecular bone volume under steady-state conditions. In contrast, after bone marrow ablation, stromal cells recruited from bone surface extensively proliferated in the marrow cavity in transgenic mice, compared to limited proliferation in wild-type mice. Whereas de novo bone formation was restricted to the ablated area in wild-type mice, the entire marrow cavity, including not only ablated area but also outside the ablated area, was filled with newly formed bone in transgenic mice. Bone mineral density was significantly increased after ablation in transgenic mice. Bone marrow cell culture in osteogenic medium revealed that alkaline phosphatase-positive area was markedly increased in the cells obtained from transgenic mice. Furthermore, mRNA expression of Wnt-signaling molecules such as LRP5, Wnt7b, and Wnt10b were upregulated after marrow ablation in bone marrow cells of transgenic mice. These results indicate that constitutive activation of PTH/PTHrP receptor in differentiated osteoblasts enhances bone marrow ablation-induced recruitment, proliferation, and differentiation of osteoprogenitors. J. Cell. Physiol. 227: 408415, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Noda, Masaki] Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Bunkyo Ku, Tokyo, Japan. [Ono, Noriaki; Nakashima, Kazuhisa; Noda, Masaki] Tokyo Med & Dent Univ, Int Res Ctr Mol Sci Tooth & Dis, Global Ctr Excellence Program, Tokyo, Japan. [Schipani, Ernestina; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Schipani, Ernestina; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA USA. [Soma, Kunimichi] Tokyo Med & Dent Univ, Grad Sch, Tokyo, Japan. [Noda, Masaki] Tokyo Med & Dent Univ, JSPS Core Core Program, ABJS Integrated Act Initiat, Tokyo, Japan. [Noda, Masaki] Tokyo Med & Dent Univ, Hard Tissue Genome Res Ctr, Tokyo, Japan. RP Noda, M (reprint author), Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Bunkyo Ku, 5-45 Yushima 1 Chome, Tokyo, Japan. EM noda.mph@mri.tmd.ac.jp RI Ezura, Yoichi/L-9485-2016 FU NIDCR NIH HHS [K99 DE022564]; NIDDK NIH HHS [P01 DK011794] NR 25 TC 11 Z9 11 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 2012 VL 227 IS 2 BP 408 EP 415 DI 10.1002/jcp.22986 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 862LQ UT WOS:000298092800002 PM 21866553 ER PT J AU Evans, CH Ghivizzani, SC Robbins, PD AF Evans, C. H. Ghivizzani, S. C. Robbins, P. D. TI Orthopedic gene therapyulost in translation? SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID RECOMBINANT ADENOASSOCIATED VECTOR; CHRONIC JOINT DISEASES; RHEUMATOID-ARTHRITIS; ANTAGONIST GENE; SAFETY; TOLERABILITY; EXPRESSION; INJECTION; DELIVERY; FUTURE AB Orthopedic gene therapy has been the topic of considerable research for two decades. The preclinical data are impressive and many orthopedic conditions are well suited to genetic therapies. But there have been few clinical trials and no FDA-approved product exists. This paper examines why this is so. The reasons are multifactorial. Clinical translation is expensive and difficult to fund by traditional academic routes. Because gene therapy is viewed as unsafe and risky, it does not attract major funding from the pharmaceutical industry. Start-up companies are burdened by the complex intellectual property environment and difficulties in dealing with the technology transfer offices of major universities. Successful translation requires close interactions between scientists, clinicians and experts in regulatory and compliance issues. It is difficult to create such a favorable translational environment. Other promising fields of biological therapy have contemplated similar frustrations approximately 20 years after their founding, so there seem to be more general constraints on translation that are difficult to define. Gene therapy has noted some major clinical successes in recent years, and a sense of optimism is returning to the field. We hope that orthopedic applications will benefit collaterally from this upswing and move expeditiously into advanced clinical trials. J. Cell. Physiol. 227: 416420, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Evans, C. H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Adv Orthopaed Studies, Boston, MA 02215 USA. [Ghivizzani, S. C.] Univ Florida, Coll Med, Dept Orthoped & Rehabil, Gene Therapy Lab, Gainesville, FL USA. [Robbins, P. D.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA. RP Evans, CH (reprint author), CAOS Beth Israel Deaconess Med Ctr, 330 Brookline Ave,RN-115, Boston, MA 02215 USA. EM cevans@bidmc.harvard.edu FU NIH [R01 AR43623, R21 AR049606, R01 AR048566, R01 AR057422, R01 AR051085, X01 NS066865]; Orthogen FX The author's research in this area has been funded by NIH grants R01 AR43623, R21 AR049606, R01 AR048566, R01 AR057422, R01 AR051085, X01 NS066865 and by Orthogen. We thank TWJ Huizinga, MD and Ryan Porter, PhD for reviewing an earlier draft of this manuscript. NR 38 TC 15 Z9 15 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 2012 VL 227 IS 2 BP 416 EP 420 DI 10.1002/jcp.23031 PG 5 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 862LQ UT WOS:000298092800003 PM 21948071 ER PT J AU Gibney, BC Chamoto, K Lee, GS Simpson, DC Miele, LF Tsuda, A Konerding, MA Wagers, A Mentzer, SJ AF Gibney, Barry C. Chamoto, Kenji Lee, Grace S. Simpson, Dinee C. Miele, Lino F. Tsuda, Akira Konerding, Moritz A. Wagers, Amy Mentzer, Steven J. TI Cross-circulation and cell distribution kinetics in parabiotic mice SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PROGENITOR CELLS; CONTRIBUTE; MIGRATION; GROWTH; REPAIR; SKIN; STEM AB Blood-borne nucleated cells participate not only in inflammation, but in tissue repair and regeneration. Because progenitor and stem cell populations have a low concentration in the blood, the circulation kinetics and tissue distribution of these cells is largely unknown. An important approach to tracking cell lineage is the use of fluorescent tracers and parabiotic models of cross-circulation. Here, we investigated the cross-circulation and cell distribution kinetics of C57/B6 GFP+/wild-type parabionts. Flow cytometry analysis of the peripheral blood after parabiosis demonstrated no evidence for a parabiotic barrier based on cell size or surface characterstics; all peripheral blood cell subpopulations in this study reached equilibrium within 14 days. Whole blood fluorescence analysis indicated that the mean exchange flow rate was 16 mu l/h or 0.66% of the circulating blood volume per hour. Studies of peripheral lymphoid organs indicated differential cell distribution kinetics. Some subpopulations, such as CD8+ and CD11c+, equilibrated in both lymph nodes and spleen indicating a residence time <28 days; in contrast, other lymphocyte subpopulations, such as B220+ and CD4+ cells, had not yet reached equilibrium at 28 days. We conclude that parabiosis can provide important insights into defining tissue distribution, residence times, and recirculating pools using fluorochrome markers of cell lineage. J. Cell. Physiol. 227: 821828, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Gibney, Barry C.; Chamoto, Kenji; Lee, Grace S.; Simpson, Dinee C.; Miele, Lino F.; Mentzer, Steven J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Adapt & Regenerat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Tsuda, Akira; Konerding, Moritz A.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Funct & Clin Anat, Mainz, Germany. [Wagers, Amy] Joslin Diabet Ctr, Dept Pathol, Boston, MA 02215 USA. RP Mentzer, SJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Adapt & Regenerat Biol, 75 Francis St, Boston, MA 02115 USA. EM smentzer@partners.org FU NIH [HL94567, HL75426, HL007734] FX Contract grant sponsor: NIH;; Contract grant numbers: HL94567, HL75426, HL007734. NR 23 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 2012 VL 227 IS 2 BP 821 EP 828 DI 10.1002/jcp.22796 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 862LQ UT WOS:000298092800045 PM 21503883 ER PT J AU Shaughnessy, M Michael, K Resnick, B AF Shaughnessy, Marianne Michael, Kathleen Resnick, Barbara TI Impact of Treadmill Exercise on Efficacy Expectations, Physical Activity, and Stroke Recovery SO JOURNAL OF NEUROSCIENCE NURSING LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SELF-EFFICACY; OLDER-ADULTS; INSULIN SENSITIVITY; PERFORMANCE; SURVIVORS; QUESTIONNAIRES; PERSPECTIVES; RELIABILITY; VALIDITY AB Stroke survivors are at high risk for cardiovascular mortality which can be in part mitigated by increasing physical activity. Self-efficacy for exercise is known to play a role in adoption of exercise behaviors. This study examines self-reported psychological outcomes in a group of 64 stroke survivors randomized to either a 6-month treadmill training program or a stretching program. Results indicated that, regardless of group, all study participants experienced increased self-efficacy (F = 2.95, p = .09) and outcome expectations for exercise (F = 13.23, p < 0.001) and improvements in activities of daily living as reported on the Stroke Impact Scale (F = 10.97, p = .002). No statistically significant between-group differences were noted, possibly because of the fact that specific interventions designed to enhance efficacy beliefs were not part of the study. Theoretically based interventions should be tested to clarify the role of motivation and potential influence on exercise and physical activity in the stroke survivor population. C1 [Shaughnessy, Marianne] US Dept Vet Affairs, Baltimore, MD USA. [Shaughnessy, Marianne] Baltimore Geriatr Res Educ & Clin Ctr, Vet Affairs Med Ctr, Baltimore, MD USA. [Shaughnessy, Marianne; Michael, Kathleen; Resnick, Barbara] Univ Maryland, Baltimore Sch Nursing, Baltimore, MD USA. RP Shaughnessy, M (reprint author), US Dept Vet Affairs, Baltimore, MD USA. EM mshaughn@grecc.umaryland.edu FU Department of Veterans Affairs and Veterans Affairs Medical Center Baltimore Geriatric Research, Education and Clinical Cente; University of Maryland School of Medicine Division of Gerontology and Geriatric Medicine; National Institute on Aging Claude D. Pepper Older Americans Independence Center [P30-AG028747]; Maryland Exercise and Robotics Center of Excellence FX This work was supported by the Department of Veterans Affairs and Veterans Affairs Medical Center Baltimore Geriatric Research, Education and Clinical Center; the University of Maryland School of Medicine Division of Gerontology and Geriatric Medicine; the National Institute on Aging Claude D. Pepper Older Americans Independence Center (P30-AG028747); and Maryland Exercise and Robotics Center of Excellence. NR 38 TC 10 Z9 10 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0888-0395 J9 J NEUROSCI NURS JI J. Neurosci. Nurs. PD FEB PY 2012 VL 44 IS 1 BP 27 EP 35 DI 10.1097/JNN.0b013e31823ae4b5 PG 9 WC Clinical Neurology; Nursing SC Neurosciences & Neurology; Nursing GA 869YS UT WOS:000298636900005 PM 22210302 ER PT J AU Cheng, T Maddox, NC Wong, AW Rahnama, R Kuo, AC AF Cheng, Tiffany Maddox, Nicole C. Wong, Andrew W. Rahnama, Ruyan Kuo, Alfred C. TI Comparison of gene expression patterns in articular cartilage and dedifferentiated articular chondrocytes SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE articular cartilage; dedifferentiation; gene expression ID MESENCHYMAL STEM-CELLS; MOUSE LIMB; CHONDROGENIC DIFFERENTIATION; SUPERFICIAL ZONE; PROGENITOR CELLS; BONE-MARROW; MARKERS; PHENOTYPE; PROTEIN; EXPANSION AB During monolayer culture, articular chondrocytes dedifferentiate into fibroblast-like cells. The mechanisms underlying this process are poorly understood. We sought to further characterize dedifferentiation by identifying an extended panel of genes that distinguish articular cartilage from dedifferentiated chondrocytes. Thirty-nine candidate marker-genes were identified from previous studies on articular-cartilage gene-expression. Real-time PCR was used to evaluate the mRNA levels for these candidates in calf articular cartilage and dedifferentiated articular chondrocytes. Twenty-two of the candidate marker genes exhibited at least a two-fold difference in gene expression in the two cell types. Twelve of these genes had at least a ten-fold difference in gene expression. Tenascin C (TNC), type I collagen (COL1A1), and hypoxia-inducible factor 1 alpha (HIF1a) showed the highest relative expression levels in dedifferentiated chonodrocytes. Type II collagen (COL2A1), type XI collagen (COL11A2), and superficial zone protein (SZP) showed the highest relative expression levels in articular cartilage. In contrast to previous findings, fibromodulin mRNA, and protein levels were higher in dedifferentiated chondrocytes. Compared to smaller subsets of markers, this panel of 12 highly differentially expressed genes may more precisely distinguish articular cartilage from dedifferentiated chondrocytes. Since many of the genes up-regulated in dedifferentiated chondrocytes are also expressed during cartilage development, dedifferentiated chondrocytes may possess features of cartilage precursor cells. (C) 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:234245, 2012 C1 [Kuo, Alfred C.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Kuo, AC (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. EM kuoac@orthosurg.ucsf.edu FU UCSF Department of Orthopaedic Surgery; Northern California Institute for Research and Education; Veterans Affairs Medical Center, San Francisco, California FX This work was supported by the UCSF Department of Orthopaedic Surgery and the Northern California Institute for Research and Education, and with resources of the Veterans Affairs Medical Center, San Francisco, California. The authors have no competing professional or financial affiliations. NR 49 TC 24 Z9 25 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD FEB PY 2012 VL 30 IS 2 BP 234 EP 245 DI 10.1002/jor.21503 PG 12 WC Orthopedics SC Orthopedics GA 869FB UT WOS:000298581200011 PM 21809379 ER PT J AU Eswara, JR Efstathiou, JA Heney, NM Paly, J Kaufman, DS McDougal, WS McGovern, F Shipley, WU AF Eswara, Jairam R. Efstathiou, Jason A. Heney, Niall M. Paly, Jonathan Kaufman, Donald S. McDougal, W. Scott McGovern, Francis Shipley, William U. TI Complications and Long-Term Results of Salvage Cystectomy After Failed Bladder Sparing Therapy for Muscle Invasive Bladder Cancer SO JOURNAL OF UROLOGY LA English DT Article DE salvage therapy; cystectomy; postoperative complications; combined modality therapy; urinary bladder neoplasms ID TRANSITIONAL-CELL CARCINOMA; 5-YEAR FOLLOW-UP; QUALITY-OF-LIFE; RADICAL CYSTECTOMY; NEOADJUVANT CHEMOTHERAPY; URINARY-DIVERSION; RADIATION; PRESERVATION; OUTCOMES; FAILURE AB Purpose: Radical cystectomy has been the standard treatment for muscle invasive bladder cancer. Combined modality therapy involving transurethral bladder tumor resection, external beam radiation and chemotherapy is an effective alternative to cystectomy in selected patients. Salvage cystectomy is reserved for those in whom combined modality therapy fails. We characterized complications associated with salvage cystectomy. Materials and Methods: From 1986 to 2007 of 348 patients undergoing bladder sparing therapy 102 (29%) underwent salvage cystectomy, 91 of whom were treated at Massachusetts General Hospital after receiving combined modality therapy for T2-T4aNxM0 bladder cancer. Patients underwent transurethral bladder tumor resection followed by chemoradiation (40 Gy). Early assessment was performed by cystoscopy/re-biopsy. Patients with complete response continued with consolidation chemoradiation (total dose 64 Gy). Immediate salvage cystectomy (50 of 91) was performed for persistent disease, while delayed salvage cystectomy (41 of 91) was performed for an invasive recurrence. Complications were classified using the Clavien system. Results: Median patient age was 69.4 years (range 27.5 to 88.9) and median living patient followup was 12 years (range 0 to 23). Of the patients 99% (90 of 91) underwent ileal diversion. Complications of any grade within 90 days occurred in 69% (63 of 91) of patients and 16% (15 of 91) experienced major complications within 90 days. Of the patients 21% (19 of 91) required hospital readmission within 90 days. The 90-day mortality rate was 2.2% (2 of 91). Significant cardiovascular/hematological complications (pulmonary embolism, myocardial infarction, deep vein thrombosis, transfusion) within 90 days were more common in the immediate than in the delayed cystectomy group (37% vs 15%, p = 0.02). Tissue healing complications (fascial dehiscence, wound infection, ureteral stricture, anastomotic stricture, stoma/loop revisions) were more common in the delayed than in the immediate cystectomy group (35% vs 12%, p = 0.05). Conclusions: Salvage cystectomy is associated with acceptable morbidity, although complication rates are slightly higher than for other cystectomy series. Immediate cystectomies have more cardiovascular/hematological complications while delayed cystectomies have more tissue healing complications. C1 [Eswara, Jairam R.; Heney, Niall M.; McDougal, W. Scott; McGovern, Francis] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Efstathiou, Jason A.; Paly, Jonathan; Shipley, William U.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Kaufman, Donald S.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Eswara, JR (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM jeswara@partners.org NR 23 TC 30 Z9 31 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2012 VL 187 IS 2 BP 463 EP 468 DI 10.1016/j.juro.2011.09.159 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 875YC UT WOS:000299070400021 PM 22177159 ER PT J AU Bauman, WA Cirnigliaro, CM La Fountaine, MF Jensen, AM Wecht, JM Kirshblum, SC Spungen, AM AF Bauman, W. A. Cirnigliaro, C. M. La Fountaine, M. F. Jensen, A. M. Wecht, J. M. Kirshblum, S. C. Spungen, A. M. TI Re: A Small-Scale Clinical Trial to Determine the Safety and Efficacy of Testosterone Replacement Therapy in Hypogonadal Men With Spinal Cord Injury Editorial Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 [Bauman, W. A.; Cirnigliaro, C. M.; La Fountaine, M. F.; Jensen, A. M.; Wecht, J. M.; Kirshblum, S. C.; Spungen, A. M.] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY USA. RP Bauman, WA (reprint author), James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2012 VL 187 IS 2 BP 558 EP 558 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 875YC UT WOS:000299070400068 ER PT J AU Yang, XP Liu, SY Kharbanda, S Stone, RM AF Yang, Xinping Liu, Suiyang Kharbanda, Surender Stone, Richard M. TI AKT1 induces caspase-mediated cleavage of the CDK inhibitor p27Kip1 during cell cycle progression in leukemia cells transformed by FLT3-ITD SO LEUKEMIA RESEARCH LA English DT Article DE FLT-ITD; AKT1; PI3K; Caspase 3; p27Kip1; Cell cycle; AML ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; KINASE INHIBITOR; POOR-PROGNOSIS; BREAST-CANCER; CONSTITUTIVE PHOSPHORYLATION; P27(KIP1) PHOSPHORYLATION; CYTOPLASMIC LOCALIZATION; ACTIVATION AB p27Kip1 cleavage and caspase-3 regulate cell cycle in human myeloma cells and B cells, however regulation of p27Kip1 cleavage during the cell cycle is not known. In BaF3-FLT3-ITD cells, p27Kip1 undergoes C-terminal cleavage. Inhibition of the PI3K/AKT pathway is associated with decreased cleavage of p27Kip1 and G1 phase arrest. A caspase-3 inhibitor reduces p27Kip1 cleavage and inhibits cell proliferation. Knockdown shRNA against AKT1 reduces cleavage of p27Kip1, inhibits caspase-3 activation, and is associated with a delay in cell cycle progression. Taken together, these findings indicate that AKT1 induces caspase-mediated cleavage of p27Kip1, required for G1-S progression in FLT3-ITD cells. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Yang, Xinping; Liu, Suiyang; Kharbanda, Surender; Stone, Richard M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Stone, RM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM rstone@partners.org FU National Cancer Institute [PO1CA5PO1CA669]; Kristen Sesselman Amico Fund FX R.M.S. is supported by grants from the National Cancer Institute (PO1CA5PO1CA669) and the Kristen Sesselman Amico Fund. NR 39 TC 1 Z9 1 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD FEB PY 2012 VL 36 IS 2 BP 205 EP 211 DI 10.1016/j.leukres.2011.09.006 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 870GZ UT WOS:000298658600016 PM 22142798 ER PT J AU Fathi, AT Arowojolu, O Swinnen, I Sato, T Rajkhowa, T Small, D Marmsater, F Robinson, JE Gross, SD Martinson, M Allen, S Kallan, NC Levis, M AF Fathi, Amir T. Arowojolu, Omotayo Swinnen, Ian Sato, Takashi Rajkhowa, Trivikram Small, Donald Marmsater, Fredrik Robinson, John E. Gross, Stefan David Martinson, Matthew Allen, Shelley Kallan, Nicholas C. Levis, Mark TI A potential therapeutic target for FLT3-ITD AML: PIM1 kinase SO LEUKEMIA RESEARCH LA English DT Article DE FLT3; Internal tandem duplication; PIM1 kinase; Acute myeloid leukemia; Targeted therapy ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; CONSTITUTIVELY ACTIVATED FLT3; IN-VITRO; NORMAL CYTOGENETICS; INHIBITS APOPTOSIS; PHOSPHORYLATES BAD; YOUNGER ADULTS; MUTATIONS AB Patients with acute myeloid leukemia (AML) and a FLT3 internal tandem duplication (ITD) mutation have a poor prognosis, and FLT3 inhibitors are now under clinical investigation. PIM1, a serine/threonine kinase, is up-regulated in FLT3-ITD AML and may be involved in FLT3-mediated leukemogenesis. We employed a PIM1 inhibitor, AR00459339 (Array Biopharma Inc.), to investigate the effect of PIM1 inhibition in FLT3-mutant AML. Like FLT3 inhibitors, AR00459339 was preferentially cytotoxic to FLT3-ITD cells, as demonstrated in the MV4-11, Molm-14, and TF/ITD cell lines, as well as 12 FLT3-ITD primary samples. Unlike FLT3 inhibitors, AR00459339 did not suppress phosphorylation of FLT3, but did promote the dephosphorylation of downstream FLT3 targets, STAT5, AKT, and BAD. Combining AR00459339 with a FLT3 inhibitor resulted in additive to mildly synergistic cytotoxic effects. AR00459339 was cytotoxic to FLT3-ITD samples from patients with secondary resistance to FLT3 inhibitors, suggesting a novel benefit to combining these agents. We conclude that PIM1 appears to be closely associated with FLT3 signaling, and that inhibition of PIM1 may hold therapeutic promise, either as monotherapy, or by overcoming resistance to FLT3 inhibitors. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Arowojolu, Omotayo; Swinnen, Ian; Sato, Takashi; Rajkhowa, Trivikram; Small, Donald; Levis, Mark] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Marmsater, Fredrik; Robinson, John E.; Gross, Stefan David; Martinson, Matthew; Allen, Shelley; Kallan, Nicholas C.] Array Biopharma Inc, Boulder, CO USA. RP Fathi, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Zero Emerson Pl,Suite 118, Boston, MA 02114 USA. EM afathi@partners.org OI Gross, Stefan/0000-0002-5645-7304 FU NCI (NCI Leukemia SPORE) [P50 CA100632-06, R01 CA128864]; American Society of Clinical Oncology FX This work was supported by grants from the NCI (NCI Leukemia SPORE P50 CA100632-06, R01 CA128864) and the American Society of Clinical Oncology (ML). Mark Levis is a Clinical Scholar of the Leukemia and Lymphoma Society. NR 54 TC 26 Z9 28 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD FEB PY 2012 VL 36 IS 2 BP 224 EP 231 DI 10.1016/j.leukres.2011.07.011 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 870GZ UT WOS:000298658600019 PM 21802138 ER PT J AU Xie, SY Xie, N Li, YJ Wang, PY Zhang, C Li, Q Liu, XL Deng, JT Zhang, C Lv, CJ AF Xie, Shuyang Xie, Ning Li, Youjie Wang, Pingyu Zhang, Chao Li, Qiang Liu, Xiaolin Deng, Jingti Zhang, Can Lv, Changjun TI Upregulation of TRB2 induced by miR-98 in the early lesions of large artery of type-2 diabetic rat SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE microRNAs; GK rat; Diabetes; TRB2; Gene expression ID AMERICAN-HEART-ASSOCIATION; ENDOTHELIAL DYSFUNCTION; INTERMEDIATE LESIONS; INSULIN-RESISTANCE; OXIDATIVE STRESS; TRIBBLES HOMOLOG; VASCULAR-LESIONS; FATTY STREAK; MICRORNAS; PATHWAY AB To characterize the roles of tribble 2 (TRB2) and its targeted microRNAs (miRNAs) in the pathogenesis of the early vascular injury involved in diabetic-2 rat. Goto-Kakizaki (GK) rat and Wistar rat were used as the animal models. Each eligible rat was killed and the rat aorta tissues were analyzed by immunohistochemistry, ELISA, reverse transcription-polymerase chain reaction (RT-PCR), and real-time PCR detection. GFP expression in RAOEC cells (rat vascular aortic endothelial cell)were detected by flow cytometry and fluorescent microscope. TRB2 gene expression was increased in endothelia cell and the adventitia of Goto-Kakizaki (GK) rat compared with Wistar rat. Next, studies using RAOEC cells showed that the TRB2 expression was inhibited by the treatment of miR-98. We further showed that the expression of miR-98 was significantly decreased in the adventitia and endomembrane at different degrees in GK rats compared with control. Finally, we validated the changes in TRB2 by studying one of the TRB2's substrates, Akt, in animal models. We expected a corresponding change in the levels of phosphorylated Akt. Indeed, our results showed that the phosphorylation of Akt at Thr 308 in the endothelial cells and phosphorylation of Akt at Ser 473 in adventitia was decreased in GK rats, compared with Wistar control. TRB2 plays important roles in the pathogenesis of diabetic-2 large artery complications at early stage, and these effects may be modulated by miR-98. Thus, targeting TRB2 and miR-98 could be considered as novel therapeutic strategies for the early large artery deficits in diabetic-2. C1 [Xie, Shuyang; Li, Youjie; Wang, Pingyu; Zhang, Chao] Binzhou Med Univ, Inst Med Mol Genet, Dept Biochem & Mol Biol, Yantai 264003, Shandong, Peoples R China. [Xie, Ning; Li, Qiang] YanTaiShan Hosp, Yantai 264000, Shandong, Peoples R China. [Liu, Xiaolin; Lv, Changjun] Binzhou Med Univ, Affiliated Hosp, Binzhou 256603, Peoples R China. [Deng, Jingti] Shandong Univ, Sch Med, Dept Biochem & Mol Biol, Jinan 250012, Peoples R China. [Zhang, Can] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA 02129 USA. [Zhang, Can] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Xie, SY (reprint author), Binzhou Med Univ, Inst Med Mol Genet, Dept Biochem & Mol Biol, Yantai 264003, Shandong, Peoples R China. EM shuyangxie@yahoo.com.cn; lucky_lcj@sina.com FU National Natural Science Foundation [30801324]; "Taishan scholar" position; Shandong Science and Technology Committee [2007BS03048, ZR2009CQ033, ZR2009CL005]; Yantai Science and Technology Committee of China [2007153, 2008162]; [NCET-10-0919] FX This study was supported by the NCET-10-0919 and National Natural Science Foundation (no. 30801324), the "Taishan scholar" position and Shandong Science and Technology Committee (no.2007BS03048, ZR2009CQ033, ZR2009CL005) and the Yantai Science and Technology Committee (no. 2007153, 2008162) of China. NR 45 TC 6 Z9 7 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD FEB PY 2012 VL 361 IS 1-2 BP 305 EP 314 DI 10.1007/s11010-011-1116-7 PG 10 WC Cell Biology SC Cell Biology GA 869OM UT WOS:000298607600035 PM 22012613 ER PT J AU Cai, GQ Atzmon, G Naj, AC Beecham, GW Barzilai, N Haines, JL Sano, M Pericak-Vance, M Buxbaum, JD AF Cai, Guiqing Atzmon, Gil Naj, Adam C. Beecham, Gary W. Barzilai, Nir Haines, Jonathan L. Sano, Mary Pericak-Vance, Margaret Buxbaum, Joseph D. TI Evidence against a role for rare ADAM10 mutations in sporadic Alzheimer Disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Association; Genetics; Mutation; Rare variation ID ASSOCIATION; GENOTYPE AB The Alzheimer amyloid protein precursor (APP) is subject to proteolysis by ADAM10 and ADAM17, precluding the formation of A beta. Recently, coding variations in ADAM10 resulting in altered function have been reported in familial Alzheimer disease (AD). The authors carried out a large-scale (n = 576: Controls, 271; AD, 305) resequencing study of ADAM10 in sporadic AD. The results do not support a significant role for ADAM10 mutations in AD. The results also make it clear that the careful examination of ancestry required in any case-control comparison is especially true with rare variations, where even a very small number of variations might form the basis of scientific conclusions. (C) 2012 Elsevier Inc. All rights reserved. C1 [Cai, Guiqing; Sano, Mary; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Atzmon, Gil; Barzilai, Nir] Albert Einstein Coll Med, Dept Med & Genet, Bronx, NY 10467 USA. [Naj, Adam C.; Beecham, Gary W.; Pericak-Vance, Margaret] Univ Miami, Hussman Inst Human Genom, Miami, FL USA. [Haines, Jonathan L.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Sano, Mary] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Buxbaum, JD (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1668, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu RI Haines, Jonathan/C-3374-2012; OI Buxbaum, Joseph/0000-0001-8898-8313 FU National Institute on Aging of the National Institutes of Health [AG010491, AG002219, AG005138]; Glenn Foundation [AG027734, AG018728, RR012248, DK020541] FX This work was supported by grants from the National Institute on Aging of the National Institutes of Health (AG010491 and AG002219, as well as pilot award to GC from the Mount Sinai Alzheimer disease Research Center/AG005138). The longevity study was supported by AG027734, AG018728, RR012248, DK020541, and RR012248 and a grant from the Glenn Foundation. JDB is the G. Harold and Leila Y. Mathers Professor of Geriatrics and Adult Development. NR 9 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2012 VL 33 IS 2 BP 416 EP U719 DI 10.1016/j.neurobiolaging.2010.03.003 PG 5 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 863NR UT WOS:000298171800020 PM 20381196 ER PT J AU Chen, LJ Yoo, SE Na, R Liu, YH Ran, QT AF Chen, Liuji Yoo, Si-Eun Na, Ren Liu, Yuhong Ran, Qitao TI Cognitive impairment and increased A beta levels induced by paraquat exposure are attenuated by enhanced removal of mitochondrial H2O2 SO NEUROBIOLOGY OF AGING LA English DT Article DE Pesticide exposure; Alzheimer's disease; Mitochondria; Oxidative stress; Beta-amyloid; Peroxiredoxin 3; Mitochondrial H2O2; Aging ID APP TRANSGENIC MICE; ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASES; SUPEROXIDE-PRODUCTION; AMYLOID HYPOTHESIS; PARKINSONS-DISEASE; OXIDATIVE STRESS; MOUSE-BRAIN; MEMORY; LIFE AB Pesticide exposure is a risk factor of Alzheimer's disease (AD). However, little is known about how pesticide exposure may promote AD pathogenesis. In this study, we investigated the effects of paraquat pesticide exposure on beta-amyloid (A beta) levels and cognition using wild-type (WT) mice and beta-amyloid precursor protein (APP) transgenic mice. Our results showed that wild-type mice and APP transgenic mice after paraquat exposure had increased oxidative damage specifically in mitochondria of cerebral cortex and exhibited mitochondrial dysfunction. Moreover, the elevated mitochondrial damage was directly correlated with impaired associative learning and memory and increased A beta levels in APP transgenic mice exposed to paraquat. Furthermore, overexpression of peroxiredoxin 3, a mitochondrial antioxidant defense enzyme important for H2O2 removal, protected against paraquat-induced mitochondrial damage and concomitantly improved cognition and decreased A beta levels in APP transgenic mice. Therefore, our results demonstrate that mitochondrial damage is a key mechanism underlying cognitive impairment and elevated amyloidogenesis induced by paraquat and that enhanced removal of mitochondrial H2O2 could be an effective strategy to ameliorate AD pathogenesis induced by pesticide exposure. Published by Elsevier Inc. C1 [Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, CSB Dept, Barshop Inst, San Antonio, TX 78245 USA. [Chen, Liuji; Yoo, Si-Eun; Na, Ren; Liu, Yuhong; Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Yoo, Si-Eun] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA. [Ran, Qitao] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Ran, QT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, CSB Dept, Barshop Inst, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM ran@uthscsa.edu FU Department of Veteran Affairs FX The study was supported by a Merit Award (QR) from the Department of Veteran Affairs. NR 34 TC 4 Z9 5 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2012 VL 33 IS 2 AR 432.e15 DI 10.1016/j.neurobiolaging.2011.01.008 PG 12 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 863NR UT WOS:000298171800052 PM 21429624 ER PT J AU DuBois, SG Stempak, D Wu, B Mokhtari, RB Nayar, R Janeway, KA Goldsby, R Grier, HE Baruchel, S AF DuBois, Steven G. Stempak, Diana Wu, Bing Mokhtari, Reza Bayat Nayar, Rakesh Janeway, Katherine A. Goldsby, Robert Grier, Holcombe E. Baruchel, Sylvain TI Circulating endothelial cells and circulating endothelial precursor cells in patients with osteosarcoma SO PEDIATRIC BLOOD & CANCER LA English DT Article DE angiogenesis; circulating endothelial cells; osteosarcoma ID PROGENITOR CELLS; GROWTH-FACTOR; PERIPHERAL-BLOOD; CANCER-PATIENTS; POOR-PROGNOSIS; ANGIOGENESIS; CARCINOMAS; EXPRESSION; SARCOMA; DISEASE AB Background Circulating endothelial cells (CECs) have been detected at increased numbers in patients with solid cancers. CECs have not been systematically evaluated in patients with osteosarcoma. Procedure. Patients 12 months to 30 years of age with newly diagnosed high-grade osteosarcoma were eligible for this prospective cohort study. Patients provided a single blood sample at study entry for CEC quantification by flow cytometry at a single reference laboratory. CECs were defined as CD146+, CD31+, CD45-, and CD133-. CEC progenitor cells (CEPs) were defined as CD146+, CD31+, CD45-, and CD133+. Results. Eighteen patients enrolled (11 males; median age 16 years; range 5-21 years). CEC counts did not differ between patients with osteosarcoma compared to seven pediatric healthy controls (median 645 cells/ml, range 60-5,320 cells/ml vs. 1,670 cells/ml, range 330-4,700 cells/ml, respectively; P 0.12). CEP counts did not differ between patients compared to controls (median 126 cells/ml, range 0-5,320 cells/ml vs. median 260 cells/ml, range 0-10,670 cells/ml, respectively; P 0.69). CEC and CEP counts did not correlate with metastatic status, tumor size, or histologic response to neoadjuvant chemotherapy. Conclusions. CEC and CEP levels are not increased in patients with osteosarcoma compared to healthy controls. CECs and CEPs do not correlate with clinical features of osteosarcoma. Alternative novel markers of disease burden and response are needed in this disease. Pediatr Blood Cancer 2012; 58: 181-184. (C) 2011 Wiley Periodicals, Inc. C1 [DuBois, Steven G.; Goldsby, Robert] UCSF, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. [Stempak, Diana; Wu, Bing; Mokhtari, Reza Bayat; Baruchel, Sylvain] Hosp Sick Children, Dept Hematol Oncol, Toronto, ON M5G 1X8, Canada. [Nayar, Rakesh] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Janeway, Katherine A.; Grier, Holcombe E.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Janeway, Katherine A.; Grier, Holcombe E.] Harvard Univ, Sch Med, Boston, MA USA. RP DuBois, SG (reprint author), UCSF, Sch Med, Dept Pediat, 505 Parnassus Ave,M646, San Francisco, CA 94143 USA. EM duboiss@peds.ucsf.edu FU Campini Foundation; Dana-Farber; NIH/NCRR/OD UCSF-CTSI [KL2 RR024130] FX Grant sponsor: Campini Foundation; Grant sponsor: Friends of Dana-Farber; Grant sponsor: NIH/NCRR/OD UCSF-CTSI; Grant number: KL2 RR024130. NR 24 TC 6 Z9 6 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 FEB PY 2012 VL 58 IS 2 BP 181 EP 184 DI 10.1002/pbc.23046 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 864RZ UT WOS:000298259000006 PM 21319292 ER PT J AU Grace, RF Long, M Kalish, LA Neufeld, EJ AF Grace, Rachael F. Long, Michelle Kalish, Leslie A. Neufeld, Ellis J. TI Applicability of 2009 international consensus terminology and criteria for immune thrombocytopenia to a clinical pediatric population SO PEDIATRIC BLOOD & CANCER LA English DT Article DE classification; immune thrombocytopenia; pediatric; terminology ID PURPURA; CHILDREN; ADULTS; CHILDHOOD; GUIDELINES AB Background Since pediatric immune thrombocytopenia (ITP) is relatively infrequent, comparisons among clinical studies are critical but have previously been limited by differences in terminology. In 2009, an international working group (IWG) developed consensus criteria to enhance comparability in future studies in adults and children. Methods. We performed a retrospective medical record review of all pediatric ITP patients seen at a single children's hospital with a first visit between 2003 and 2010 and ;applied both historical (criteria(Hist)) and IWG (criteria(IWG)) ITP criteria to available clinical data. Results. Among the 505 patients seen for ITP over 7 years, 98% could be classified as "acute" or "chronic" ITP using the criteriaHist, while only 90.7% could be classified as "newly diagnosed," "persistent," or "chronic" ITP using the criteriaIWG (P < 0.01). Only 33.7% met criteriaIWG for severe ITP, whereas 77.4% met criteriaHist for severe ITP. A striking difference was that overall response to therapies was lower if the criteriaIWG were used rather than the criteriaHist, particularly for IVIG (55.4% vs. 70%, P = 0.02) and rituximab (35.3% vs. 83.3% P = 0.05). Only 2 subjects (0.4%) met the criteriaIWG for refractory ITP. Conclusions. Most ITP patients could easily be classified using the 2009 criteriaIWG. Limitations to applying the criteriaIWG included absence of treatment response durations, incomplete definition of pediatric "refractory ITP," and exclusion of secondary ITP. Nevertheless, the criteriaIWG were more clinically relevant given the reliance on definitions based on bleeding and their ability to be applied prospectively. The utility of using the criteriaIWG within prospective trials remains to be determined. Pediatr Blood Cancer 2012; 58: 216-220. (C) 2011 Wiley Periodicals, Inc. C1 [Grace, Rachael F.; Long, Michelle; Neufeld, Ellis J.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Grace, Rachael F.; Neufeld, Ellis J.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Grace, Rachael F.; Kalish, Leslie A.; Neufeld, Ellis J.] Harvard Univ, Sch Med, Boston, MA USA. [Kalish, Leslie A.] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. RP Grace, RF (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave,Karp 8, Boston, MA 02115 USA. EM rachael.grace@childrens.harvard.edu OI Grace, Fergal/0000-0002-3144-5999 FU NIH [K24 HL004184]; National Hemophilia Foundation; American Society of Hematology; The Harvard Clinical and Translational Science Center [UL1 RR 025758]; Harvard University FX Grant sponsor: NIH; Grant number: K24 HL004184; Grant sponsor: National Hemophilia Foundation; Grant sponsor: American Society of Hematology Student Research Grant.; This work was conducted with support from the Scholars in Clinical Science program of Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (Award #UL1 RR 025758 to RFG and financial contributions from Harvard University and its affiliated academic health care centers). Grant support includes: NIH Grant number: K24 HL004184 (EJN); National Hemophilia Foundation (RFG); and the American Society of Hematology Student Research Grant (ML). NR 14 TC 5 Z9 7 U1 2 U2 4 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 FEB PY 2012 VL 58 IS 2 BP 216 EP 220 DI 10.1002/pbc.23112 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 864RZ UT WOS:000298259000011 PM 21674757 ER PT J AU Grace, RF Bennett, CM Ritchey, AK Jeng, M Thornburg, CD Lambert, MP Neier, M Recht, M Kumar, M Blanchette, V Klaassen, RJ Buchanan, GR Kurth, MH Nugent, DJ Thompson, AA Stine, K Kalish, LA Neufeld, EJ AF Grace, Rachael F. Bennett, Carolyn M. Ritchey, A. Kim Jeng, Michael Thornburg, Courtney D. Lambert, Michele P. Neier, Michelle Recht, Michael Kumar, Manjusha Blanchette, Victor Klaassen, Robert J. Buchanan, George R. Kurth, Margaret Heisel Nugent, Diane J. Thompson, Alexis A. Stine, Kimo Kalish, Leslie A. Neufeld, Ellis J. TI Response to steroids predicts response to rituximab in pediatric chronic immune thrombocytopenia SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material DE ITP; pediatric; rituximab; treatment ID CELL-DEPLETING THERAPY; INTRAVENOUS IMMUNOGLOBULIN; ADULT PATIENTS; PURPURA; SPLENECTOMY; CHILDREN; CHILDHOOD; MANAGEMENT; GLOBULIN; ITP AB Background Treatment choice in pediatric immune thrombocytopenia (ITP) is arbitrary, because few studies are powered to identify predictors of therapy response. Increasingly, rituximab is becoming a treatment of choice in those refractory to other therapies. Methods. The objective of this study was to evaluate univariate and multivariable predictors of platelet count response to rituximab. After local IRB approval, 565 patients with chronic ITP enrolled and met criteria for this study in the longitudinal, North American Chronic ITP Registry (NACIR) between January 2004 and October 2010. Treatment response was defined as a post-treatment platelet count >= 50,000/mu l within 16 weeks of rituximab and 14 days of steroids. Treatment response data were captured both retrospectively at enrollment and then prospectively. Results. Eighty (14.2%) patients were treated with rituximab with an overall response rate of 63.8% (51/ 80). Univariate correlates of response to rituximab included the presence of secondary ITP and a positive response to steroids. In multivariable analysis, response to steroids remained a strong correlate of response to rituximab, OR 6.8 (95% CI 2.0-23.0, P = 0.002). Secondary ITP also remained a strong predictor of response to rituximab, OR 5.6 (95% CI 1.1-28.6, P = 0.04). Although 87.5% of patients who responded to steroids responded to rituximab, 48% with a negative response to steroids did respond to rituximab. Conclusion. In the NACIR, response to steroids and presence of secondary ITP were strong correlates of response to rituximab, a finding not previously reported in children or adults. Pediatr Blood Cancer 2012; 58: 221-225. (C) 2011 Wiley Periodicals, Inc. C1 [Grace, Rachael F.; Neufeld, Ellis J.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Grace, Rachael F.; Neufeld, Ellis J.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Grace, Rachael F.; Kalish, Leslie A.; Neufeld, Ellis J.] Harvard Univ, Sch Med, Boston, MA USA. [Bennett, Carolyn M.] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Aflac Canc Ctr & Blood Disorders Serv, Atlanta, GA USA. [Ritchey, A. Kim] Childrens Hosp Pittsburgh UPMC, Pittsburgh, PA USA. [Jeng, Michael] Lucile Packard Childrens Hosp, Palo Alto, CA USA. [Thornburg, Courtney D.] Duke Univ, Med Ctr, Durham, NC USA. [Lambert, Michele P.] Childrens Hosp, Philadelphia, PA 19104 USA. [Neier, Michelle] Robert Wood Johnson Univ Hosp, Canc Inst New Jersey, New Brunswick, NJ USA. [Recht, Michael] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kumar, Manjusha] Riley Hosp Children, Indianapolis, IN USA. [Blanchette, Victor] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Klaassen, Robert J.] Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. [Buchanan, George R.] Univ Texas SW Med Ctr Dallas, Dallas, TX USA. [Kurth, Margaret Heisel] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA. [Nugent, Diane J.] Childrens Hosp Orange Cty, Orange, CA 92668 USA. [Thompson, Alexis A.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Stine, Kimo] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Kalish, Leslie A.] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. RP Grace, RF (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave,Karp 8, Boston, MA 02115 USA. EM rachael.grace@childrens.harvard.edu OI Grace, Fergal/0000-0002-3144-5999 FU NCRR NIH HHS [UL1 RR 025758, UL1 RR025758]; NHLBI NIH HHS [K24 HL004184] NR 28 TC 8 Z9 9 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 FEB PY 2012 VL 58 IS 2 BP 221 EP 225 DI 10.1002/pbc.23130 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 864RZ UT WOS:000298259000012 PM 21674758 ER PT J AU Chang, G Ratichek, SJ Recklitis, C Syrjala, K Patel, SK Harris, L Rodday, AM Tighiouart, H Parsons, SK AF Chang, Grace Ratichek, Sara J. Recklitis, Christopher Syrjala, Karen Patel, Sunita K. Harris, Lynnette Rodday, Angie Mae Tighiouart, Hocine Parsons, Susan K. TI Children's psychological distress during pediatric HSCT: Parent and child perspectives SO PEDIATRIC BLOOD & CANCER LA English DT Article DE child; parent; psychological distress ID QUALITY-OF-LIFE; STEM-CELL TRANSPLANTATION; PRIMARY-CARE; SUBSYNDROMAL DEPRESSION; CANCER SURVIVOR; ADULT SURVIVORS; SYMPTOMS; OUTCOMES; DISORDERS; ONCOLOGY AB Background Hematopoietic stem cell transplantation (HSCT) can be challenging to pediatric recipients and their families. Little is known about the recipients' psychological status as they initiate treatment and in the year afterwards. The purpose of this study is to describe the psychological status of 107 pediatric HSCT recipients from their parents' perspective, and to compare reports from parents and children in a subset of 55 children. We hypothesized that there would be discrepancies between parent and child report of child distress. Procedure. Multi-site, prospective study of eligible child participants and their parents who completed selected modules from the Structured Clinical Interview for DSM-IV-TR, Childhood Version (KID-SCID) the month before and one year after HSCT. Diagnoses were threshold or subthreshold. Results. According to parents, nearly 30% of children had anxiety disorder both before and after HSCT; approximately half of these met threshold criteria. Agreement between parents and children for anxiety disorders was poor at baseline (kappa = 0.18, 95% CI = -0.33, -0.02) and fair at 12 months (kappa = 0.31, 95% CI = -0.04, 0.66). Agreement about mood disorders was fair at baseline (10% prevalence, kappa = 0.39, 95% CI = -0.02, 0.79) and moderate at 12 months (14% prevalence, kappa = 0.41, 95% CI 0.02, 0.80). Conclusions. Anxiety (30%) and mood (10-14%) symptoms are common in children both before and after HSCT; parent and child reports of these symptoms do not agree. Input from parents and children is recommended to identify more accurately children who may need additional intervention during and following HSCT Pediatr Blood Cancer 2012; 58: 289-296. (C) 2011 Wiley Periodicals, Inc. C1 [Chang, Grace] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Chang, Grace] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Ratichek, Sara J.; Rodday, Angie Mae; Tighiouart, Hocine; Parsons, Susan K.] Tufts Med Ctr, Inst Clin Res Hlth Policy Studies, Boston, MA USA. [Recklitis, Christopher] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Syrjala, Karen] Fred Hutchinson Canc Res Ctr, Dept Behav Sci, Seattle, WA 98104 USA. [Patel, Sunita K.] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA 91010 USA. [Patel, Sunita K.] City Hope Natl Med Ctr, Dept Pediat Support Care Med, Duarte, CA 91010 USA. [Harris, Lynnette] Texas Childrens Hosp, Dept Pediat, Houston, TX 77030 USA. [Parsons, Susan K.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Parsons, Susan K.] Tufts Univ, Sch Med, Dept Pediat, Boston, MA 02111 USA. RP Chang, G (reprint author), Brigham & Womens Hosp, Dept Psychiat, 221 Longwood Ave, Boston, MA 02115 USA. EM gchang@partners.org FU American Cancer Society [RSG PB02-186-01-PBP, R01 CA 119196, K24 AA 000289] FX Grant sponsor: American Cancer Society; Grant numbers: RSG PB02-186-01-PBP, R01 CA 119196, K24 AA 000289. NR 34 TC 8 Z9 8 U1 2 U2 3 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 FEB PY 2012 VL 58 IS 2 BP 289 EP 296 DI 10.1002/pbc.23185 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 864RZ UT WOS:000298259000023 PM 21618413 ER PT J AU Ritter, BP Angelo, GW Durner, M Rossy-Fullana, E Carrion-Baralt, J Silverman, JM Bespalova, IN AF Ritter, Benjamin P. Angelo, Gary W. Durner, Martina Rossy-Fullana, Enrique Carrion-Baralt, Jose Silverman, Jeremy M. Bespalova, Irina N. TI Mutation screening of PDZD2, GOLPH3, and MTMR12 genes in patients with schizophrenia SO PSYCHIATRIC GENETICS LA English DT Editorial Material ID DISORDERS; RECEPTOR; LOCUS C1 [Ritter, Benjamin P.; Angelo, Gary W.; Durner, Martina; Silverman, Jeremy M.; Bespalova, Irina N.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Ritter, Benjamin P.; Angelo, Gary W.; Durner, Martina; Silverman, Jeremy M.; Bespalova, Irina N.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Rossy-Fullana, Enrique] San Juan Vet Affairs Med Ctr, San Juan, PR USA. [Carrion-Baralt, Jose] Univ Puerto Rico, San Juan, PR 00936 USA. RP Bespalova, IN (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave Levy Pl,POB 1230, New York, NY 10029 USA. EM irina.bespalova@mssm.edu FU NIMH NIH HHS [R03MH082134] NR 6 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD FEB PY 2012 VL 22 IS 1 BP 51 EP 52 DI 10.1097/YPG.0b013e3283463dd7 PG 2 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 866JN UT WOS:000298376800008 PM 21451436 ER PT J AU Sundaram, M Hodler, J Rosenthal, DI AF Sundaram, Murali Hodler, Juerg Rosenthal, Daniel I. TI On the relevance of the Impact Factor and other factors SO SKELETAL RADIOLOGY LA English DT Editorial Material C1 [Sundaram, Murali] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Hodler, Juerg] Univ Spital Zurich, Inst Diagnost & Intervent Radiol, Zurich, Switzerland. [Rosenthal, Daniel I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sundaram, M (reprint author), Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM sundarm@ccf.org NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD FEB PY 2012 VL 41 IS 2 BP 125 EP 126 DI 10.1007/s00256-011-1342-9 PG 2 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 866CP UT WOS:000298357500001 PM 22170183 ER PT J AU Huang, AJ Palmer, WE AF Huang, Ambrose J. Palmer, William E. TI Incidence of inadvertent intra-articular lumbar facet joint injection during fluoroscopically guided interlaminar epidural steroid injection SO SKELETAL RADIOLOGY LA English DT Article DE Radiology; Interventional; Epidural injections; Facet joint; Zygapophyseal joint; Spine ID ARTHROGRAPHY; SPREAD; SPONDYLOLYSIS; DISABILITY AB To determine the incidence of inadvertent lumbar facet joint injection during an interlaminar epidural steroid injection (ESI). A total of 686 interlaminar lumbar ESIs were performed from January 1, 2009 to December 31, 2009. Archived images from these cases were retrospectively reviewed on the PACS. Positive cases of inadvertent lumbar facet joint injection were identified by the characteristic sigmoid-shaped contrast pattern projecting over the posterior elements on the lateral view and/or ovoid contrast projecting over the facet joints on the anteroposterior (AP) view. Eight positive events were identified (1.2%). There was no statistically significant gender or lumbar level predilection. In 3/8 of the positive cases (37.5%), the inadvertent facet joint injection was recognized by the operator. The needle was repositioned as a result, and contrast within the posterior epidural space was documented by the end of the procedure. In 5/8 of the positive cases (62.5%), the patients reported an immediate decrease in the presenting pain. The incidence of inadvertent lumbar facet joint injection during an interlaminar epidural steroid injection is low. Recognizing the imaging features of this event permits the operator to redirect the needle tip into the epidural space and/or identify the facet joint(s) as a source of the patient's presenting pain. C1 [Huang, Ambrose J.; Palmer, William E.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. RP Huang, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM ajhuang@partners.org; wpalmer@partners.org NR 16 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD FEB PY 2012 VL 41 IS 2 BP 157 EP 162 DI 10.1007/s00256-011-1332-y PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 866CP UT WOS:000298357500006 PM 22159989 ER PT J AU Bateman, BT Bansil, P Hernandez-Diaz, S Mhyre, JM Callaghan, WM Kuklina, EV AF Bateman, Brian T. Bansil, Pooja Hernandez-Diaz, Sonia Mhyre, Jill M. Callaghan, William M. Kuklina, Elena V. TI Prevalence, trends, and outcomes of chronic hypertension: a nationwide sample of delivery admissions SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE chronic hypertension; epidemiology; obstetric complications ID MILD CHRONIC HYPERTENSION; RISK-FACTORS; PREGNANCY; WOMEN; METAANALYSIS; STILLBIRTH; DISORDERS; MORBIDITY; STATES AB OBJECTIVE: We sought to define the prevalence, trends, and outcomes of primary and secondary chronic hypertension in a population-based sample of deliveries. STUDY DESIGN: An estimated 56,494,634 deliveries were identified from the 1995 through 2008 Nationwide Inpatient Sample. The association of primary and secondary chronic hypertension with adverse fetal and maternal outcomes was evaluated using regression modeling and adjusted population-attributable fractions were calculated. RESULTS: During the study period, the prevalence of primary and secondary hypertension increased from 0.90% in 1995 through 1996 to 1.52% in 2007 through 2008 (P for trend <.001) and from 0.07% to 0.24% (P for trend <.001), respectively. The population-attributable fraction for chronic hypertension was considerable for many maternal adverse outcomes, including acute renal failure (21%), pulmonary edema (14%), preeclampsia (11%), and in-hospital mortality (10%). CONCLUSION: Primary and secondary chronic hypertension were both strongly associated with adverse pregnancy outcomes and accounted for a substantial fraction of maternal morbidity. Prioritizing research efforts in this area is needed. C1 [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Div Obstet Anesthesia, Dept Anesthesia Crit Care & Pain Med,Sch Med, Boston, MA 02114 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. [Bansil, Pooja; Kuklina, Elena V.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Heart Dis & Stroke Prevent, Atlanta, GA USA. [Callaghan, William M.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, Atlanta, GA USA. [Mhyre, Jill M.] Univ Michigan Hlth Syst, Dept Anesthesiol, Ann Arbor, MI USA. RP Bateman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Obstet Anesthesia, Dept Anesthesia Crit Care & Pain Med,Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM BBateman@partners.org FU NIGMS NIH HHS [T32 GM007592] NR 24 TC 1 Z9 1 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2012 VL 206 IS 2 AR 134.e1 DI 10.1016/j.ajog.2011.10.878 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 886FA UT WOS:000299836800018 PM 22177190 ER PT J AU You, JJ Singer, DE Howard, PA Lane, DA Eckman, MH Fang, MC Hylek, EM Schulman, S Go, AS Hughes, M Spencer, FA Manning, WJ Halperin, JL Lip, GYH AF You, John J. Singer, Daniel E. Howard, Patricia A. Lane, Deirdre A. Eckman, Mark H. Fang, Margaret C. Hylek, Elaine M. Schulman, Sam Go, Alan S. Hughes, Michael Spencer, Frederick A. Manning, Warren J. Halperin, Jonathan L. Lip, Gregory Y. H. TI Antithrombotic Therapy for Atrial Fibrillation Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines SO CHEST LA English DT Article AB Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS(2) [congestive heart failure, hypertension, age >= 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS(2) score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS(2) score of >= 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS(2) score of >= 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach. C1 [You, John J.; Schulman, Sam; Spencer, Frederick A.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [You, John J.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Singer, Daniel E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. [Howard, Patricia A.] Univ Kansas, Med Ctr, Sch Pharm, Kansas City, KS 66103 USA. [Lane, Deirdre A.; Lip, Gregory Y. H.] Univ Birmingham, City Hosp, Ctr Cardiovasc Sci, Birmingham B18 7QH, W Midlands, England. [Eckman, Mark H.] Univ Cincinnati, Dept Clin Med, Div Gen Internal Med, Cincinnati, OH USA. [Eckman, Mark H.] Univ Cincinnati, Ctr Clin Effectiveness, Cincinnati, OH USA. [Fang, Margaret C.] Univ Calif San Francisco, Dept Med, Div Hosp Med, San Francisco, CA USA. [Hylek, Elaine M.] Boston Univ, Med Res Ctr, Gen Internal Med Sect, Boston, MA 02215 USA. [Go, Alan S.] Kaiser Permanente No Calif, Comprehens Clin Res Unit, Div Res, Oakland, CA USA. [Hughes, Michael] Decis Resources Inc, London, England. [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Sect Noninvas Cardiac Imaging, Boston, MA 02215 USA. [Halperin, Jonathan L.] Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA. RP Lip, GYH (reprint author), Univ Birmingham, City Hosp, Ctr Cardiovasc Sci, Birmingham B18 7QH, W Midlands, England. EM g.y.h.lip@bham.ac.uk OI Schulman, Sam/0000-0002-8512-9043 FU National Heart, Lung, and Blood Institute [R13 HL104758]; Bayer Schering Pharma AG; Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; sanofi-aventis US FX The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758] and Bayer Schering Pharma AG. Support in the form of educational grants was also provided by Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; and sanofi-aventis US. NR 175 TC 251 Z9 266 U1 0 U2 9 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD FEB PY 2012 VL 141 IS 2 SU S BP E531S EP E575S DI 10.1378/chest.11-2304 PG 45 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V30UC UT WOS:000208839900015 PM 22315271 ER PT J AU Katz, DL Daniels, S Gardner, CD Goodman, E Hassink, S Sothern, M AF Katz, David L. Daniels, Stephen Gardner, Christopher D. Goodman, Elizabeth Hassink, Sandra Sothern, Melinda TI What We Don't Know: Unanswered Questions about Childhood Obesity SO CHILDHOOD OBESITY LA English DT Editorial Material C1 [Katz, David L.] Yale Univ, Prevent Res Ctr, Derby, CT USA. [Daniels, Stephen] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA. [Gardner, Christopher D.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. [Goodman, Elizabeth] MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA USA. [Hassink, Sandra] Nemours Childrens Hlth Syst, Nemours Obes Initiat, Wilmington, DE USA. [Sothern, Melinda] Louisiana State Univ, Sch Publ Hlth, Hlth Sci Ctr, New Orleans, LA USA. RP Katz, DL (reprint author), Yale Univ, Prevent Res Ctr, Derby, CT USA. OI Katz, David/0000-0001-6845-6192 NR 0 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-2168 EI 2153-2176 J9 CHILD OBES JI Child Obes. PD FEB PY 2012 VL 8 IS 1 BP 7 EP 12 DI 10.1089/chi.2011.0800.roun PG 6 WC Pediatrics SC Pediatrics GA V32JG UT WOS:000208946900005 PM 22799470 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Competing Influences in the Management of Gastrointestinal Bleeding SO CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY LA English DT Article AB OBJECTIVES: Management of gastrointestinal (GI) bleeding centers on the issues of location, type of mucosal lesion, effects of anticoagulation, diagnosis, and therapy. Each one of these five individual factors is affected by multiple interactions with the other coexisting factors. The aim of the present study is to analyze which set of factors ultimately exerts the largest and most lasting influence on the disease process. METHODS: The interactions among the five contributing factors are analyzed using a transposed Markov chain model. RESULTS: The analysis reveals that, in declining order, location, anticoagulation, and type of lesion exert the largest influence on the disease process. Under steady state conditions, their magnitudes of influence are 50, 33, and 17%, respectively. The other two factors, diagnosis and therapy, result as a consequence of the aforementioned three primary factors, but do not exert any major influence themselves. The outcome of the analysis remains robust to multiple wide-ranging variations in the assumptions underlying the model. CONCLUSIONS: The model of a transposed Markov chain translates an initially bewildering array of interacting influences into a coherent and transparent model of gastrointestinal bleeding. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Dept Gastroenterol, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Dept Gastroenterol, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 7 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2155-384X J9 CLIN TRANSL GASTROEN JI Clin. Transl. Gastroenterol. PD FEB PY 2012 VL 3 AR e8 DI 10.1038/ctg.2012.3 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V42QA UT WOS:000209627100001 PM 23238133 ER PT J AU Tanpowpong, P Broder-Fingert, S Katz, AJ Camargo, CA AF Tanpowpong, Pornthep Broder-Fingert, Sarabeth Katz, Aubrey J. Camargo, Carlos A., Jr. TI Age-Related Patterns in Clinical Presentations and Gluten-Related Issues Among Children and Adolescents With Celiac Disease SO CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY LA English DT Article AB OBJECTIVES: Celiac disease (CD) is common and often cited as an "iceberg'' phenomenon (i.e., an assumed large number of undiagnosed cases). Recently, atypical or asymptomatic manifestations are becoming more commonly described in older children and adolescents. Moreover, CD diagnosis in children can be complicated by several factors, including its diverse clinical presentations, delay in recognizing CD signs and symptoms, and premature dietary gluten avoidance before the formal diagnosis of CD. To date, few studies have directly examined age-related differences in clinical characteristics and gluten-related issues among children with CD. The aim of this study was to determine age-related patterns in clinical characteristics and gluten-related issues among children with confirmed CD. METHODS: We performed a structured medical record review of biopsy-proven CD patients, aged 0-19 years, between 2000 and 2010 at a large Boston teaching hospital. Data collection included demographics, medical history, gluten-related issues, and diagnostic investigations (CD-specific serology, upper gastrointestinal endoscopy, and small intestinal biopsy). The first positive duodenal biopsy with Marsh III classification defined age of diagnosis. Patients were divided into three age groups for comparisons of the aforementioned characteristics: infant-preschool group (0-5 years), school-aged group (6-11 years), and adolescence group (12-19 years). RESULTS: Among 411 children with biopsy-proven CD, the mean age was 9.5 (s.d. 5.1) years. Most were female (63%) and white (96%). All children had positive CD-specific serology. Most children presented with either abdominal complaints or bowel movement changes. Overall, boys were more common among infant-preschool group compared with the other age groups. More distinct clinical manifestations (vomiting, bowel movement changes, and weight issues) were apparent in the youngest group, whereas school-aged children had more subjective abdominal complaints at the initial presentation. Conversely, the adolescents were most likely to present without any gastrointestinal (GI) symptoms, but not when this was combined with absence of weight issues. Age of diagnosis was not associated with atypical extraintestinal CD presentations. Regarding the gluten-related issues, 10% of school-aged children avoided dietary gluten before the formal CD diagnosis, and 27% of the adolescents reported dietary gluten transgression within the first 12 months of diagnosis, significantly higher than the other age groups. Age differences in histopathology were also found. Whereas the infant-preschool group had a higher proportion of total villous atrophy, the older children were more likely to have gross duodenal abnormalities and chronic duodenitis suggestive of CD at the time of diagnosis. CONCLUSIONS: Children and adolescents with CD have age-related patterns in both the clinical presentations and gluten-related issues. More pronounced clinical and histological features were determined in younger children, whereas older children more commonly presented with solely subjective abdominal complaints or even without any GI symptoms. However, silent and atypical extraintestinal CD presentations were comparable between age groups. In addition to the aforementioned presentations, the higher rates of dietary gluten avoidance and transgression in older children make CD diagnosis and management particularly challenging. These age-related patterns may further increase awareness, facilitate early diagnosis, and improve patient care of pediatric CD. C1 [Tanpowpong, Pornthep; Broder-Fingert, Sarabeth; Katz, Aubrey J.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp Children, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org OI Broder-Fingert, Sarabeth/0000-0002-0932-4461 NR 30 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2155-384X J9 CLIN TRANSL GASTROEN JI Clin. Transl. Gastroenterol. PD FEB PY 2012 VL 3 AR e9 DI 10.1038/ctg.2012.4 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V42QA UT WOS:000209627100002 PM 23238134 ER PT J AU Weil, AA Ivers, LC Harris, JB AF Weil, Ana A. Ivers, Louise C. Harris, Jason B. TI Cholera: Lessons from Haiti and Beyond SO CURRENT INFECTIOUS DISEASE REPORTS LA English DT Article DE Cholera; Endemic; Epidemic; Vibrio cholerae; Cholera toxin; Oral rehydration solution; Herd immunity; Case fatality rate ID SINGLE-DOSE AZITHROMYCIN; VIBRIO-CHOLERAE; CHILDHOOD DIARRHEA; ENDEMIC CHOLERA; BANGLADESH; INFECTION; RISK; PREVENTION; VACCINES; TRIAL AB Cholera is an acute, severe diarrheal disease caused by Vibrio cholerae that affects millions of people each year. Without prompt rehydration, death can occur within hours of the onset of symptoms. In October 2010, cholera emerged in Haiti, and the resulting large epidemic continues today. As of August 29, 2011, more than 439,000 cases have been reported in Haiti, with over 6,200 deaths. This review covers important features of epidemiology, pathogenesis, treatment and prevention of cholera, with a focus on the ongoing epidemic in Haiti. C1 [Weil, Ana A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Ivers, Louise C.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Ivers, Louise C.] Harvard Univ, Sch Med, Dept Global Hlth, Boston, MA USA. [Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM jbharris@partners.org FU International Research Scientist Development Award from the National Institutes of Health [K01 TW07409]; Fogarty International Center; Charles H. Hood Foundation Child Health Research Award FX The authors thank Russ Johnson for the manuscript photographs. JBH is supported by an International Research Scientist Development Award (K01 TW07409) from the National Institutes of Health, Fogarty International Center and a Charles H. Hood Foundation Child Health Research Award. NR 60 TC 6 Z9 7 U1 4 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3847 EI 1534-3146 J9 CURR INFECT DIS REP JI Curr. Infect. Dis. Rep. PD FEB PY 2012 VL 14 IS 1 BP 1 EP 8 DI 10.1007/s11908-011-0221-9 PG 8 WC Infectious Diseases SC Infectious Diseases GA V32XC UT WOS:000208982900001 PM 22179934 ER PT J AU Stone, VE AF Stone, Valerie E. TI HIV/AIDS in Women and Racial/Ethnic Minorities in the US SO CURRENT INFECTIOUS DISEASE REPORTS LA English DT Article DE Women; HIV/AIDS; Pregnancy; Hormones; Racial/ethnic minorities; Epidemiology; Linkage to care; Engagement in care; Disparities; Prevention AB The clinical issues affecting women with HIV/AIDS differ little from those affecting men. However, current research shows that treatment and outcome disparities affect many women with HIV, hypothesized to result from a complex interplay of socioeconomic and gender role influences. These disparities are also a reflection of racial/ethnic differences in treatment and outcome, since 80% of women with HIV/AIDS are black or Hispanic. Women have unique needs for HIV prevention - both prevention of sexual transmission to or from sexual partners and prevention of perinatal transmission. Racial/ethnic minorities continue to be disproportionately affected by the HIV/AIDS epidemic in the U. S. Minorities are less likely to be in care and on HAART than others with HIV/AIDS. These disparities result in poorer outcomes for minorities, especially blacks, with HIV/AIDS. New strategies for optimizing engagement and retention in care, and for prevention hold great promise for women and minorities with HIV in the U.S. C1 [Stone, Valerie E.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Stone, Valerie E.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Stone, Valerie E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Stone, VE (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, 55 Fruit St,Bulfinch 130, Boston, MA 02114 USA. EM vstone@partners.org FU Gilead Sciences; Tibotec Therapeutics FX V. Stone has received honoraria and consulting fees from Gilead Sciences and Tibotec Therapeutics. NR 40 TC 12 Z9 12 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3847 EI 1534-3146 J9 CURR INFECT DIS REP JI Curr. Infect. Dis. Rep. PD FEB PY 2012 VL 14 IS 1 BP 53 EP 60 DI 10.1007/s11908-011-0226-4 PG 8 WC Infectious Diseases SC Infectious Diseases GA V32XC UT WOS:000208982900008 PM 22139589 ER PT J AU Nashel, J Steen, V AF Nashel, Jennifer Steen, Virginia TI Scleroderma Mimics SO CURRENT RHEUMATOLOGY REPORTS LA English DT Article DE Scleroderma mimics; Morphea; Localized scleroderma; Scleredema; Scleredema of Buschke; Scleredema adultorum; Scleredema diabeticorum; Diabetic cheiroarthropathy; Limited joint mobility syndrome; Scleromyxedema; Lichen myxedematosus; Nephrogenic systemic fibrosis; Eosinophilic fasciitis ID NEPHROGENIC SYSTEMIC FIBROSIS; OF-THE-LITERATURE; ULTRAVIOLET A1 PHOTOTHERAPY; EOSINOPHILIC FASCIITIS; LOCALIZED SCLERODERMA; SCLEREDEMA DIABETICORUM; SCLEROMYXEDEMA; DISEASE; SKIN; TRANSPLANTATION AB Scleroderma is a rare systemic autoimmune disease with multiple organ manifestations, including skin fibrosis. The groups of disorders classified as scleroderma mimics share the common thread of skin thickening but are otherwise quite incongruous in terms of underlying disease process and other organ involvement. This article reviews the clinical presentation, etiology, and treatment options available for scleroderma mimics, including morphea, scleredema, diabetic cheiroarthropathy, scleromyxedema, nephrogenic systemic fibrosis, and eosinophilic fasciitis. Through greater understanding of these diseases and the associated extradermal implications, we hope to facilitate recognition of scleroderma and its mimics. C1 [Nashel, Jennifer] Harvard Univ, Sch Med, Div Rheumatol, BIDMC, Boston, MA 02215 USA. [Nashel, Jennifer] Harvard Univ, Sch Med, Lupus Ctr, Boston, MA 02215 USA. [Steen, Virginia] Georgetown Univ, Sch Med, Washington, DC 20007 USA. RP Steen, V (reprint author), Georgetown Univ, Sch Med, 3800 Reservoir Rd,PHC 3004, Washington, DC 20007 USA. EM steenv@georgetown.edu NR 37 TC 9 Z9 12 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3774 J9 CURR RHEUMATOL REP JI Curr. Rheumatol. Rep. PD FEB PY 2012 VL 14 IS 1 BP 39 EP 46 DI 10.1007/s11926-011-0220-8 PG 8 WC Rheumatology SC Rheumatology GA 224NQ UT WOS:000324894300005 PM 22131103 ER PT J AU Barkoudah, E Skali, H Uno, H Solomon, SD Pfeffer, MA AF Barkoudah, Ebrahim Skali, Hicham Uno, Hajime Solomon, Scott D. Pfeffer, Marc A. TI Mortality Rates in Trials of Subjects With Type 2 Diabetes SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE type 2 diabetes; chronic kidney disease; mortality; controlled clinical trials; randomized ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC KIDNEY-DISEASE; PLACEBO-CONTROLLED TRIAL; BLOOD-GLUCOSE CONTROL; CARDIOVASCULAR-DISEASE; PRIMARY PREVENTION; DARBEPOETIN-ALPHA; CLINICAL-TRIALS; MELLITUS; RISK AB Background-In randomized controlled trials (RCTs) of subjects with type 2 diabetes mellitus, mortality rates vary substantially. We sought to examine the inclusion and exclusion criteria of these RCTs to explore relationships with mortality. Methods and Results-MEDLINE database was searched from August 1980 through March 2011. Selection criterion included published RCTs of adults with type 2 diabetes mellitus of at least 1000 patients, reporting all-cause mortality and having follow-up duration of at least 1 year. Twenty-two trials were eligible. Annualized mortality rates were derived. Inclusion and exclusion criteria were tabulated for each trial. Trials were categorized in 4 groups according to annual mortality rates: <1, >= 1 to <2, >= 2 to <4, and >= 4 per 100 patient-years. The analysis cohort included 91842 patients and 6837 deaths. Mortality rates ranged from 0.28 to 8.24 per 100 patient-years. Patients enrolled in the highest mortality category were more likely to be older and had longer diabetes duration and higher blood pressure. The selection for hypertension was common in the low-as well as high-mortality trials. Although the mortality rates were higher in RCTs with prior cardiovascular morbidity, the selection for chronic kidney disease-defined by either higher serum creatinine or lower estimated glomerular filtration rate and/or the presence of proteinuria-was associated with the highest mortality rates. Conclusions-In this analysis of RCTs of type 2 diabetes mellitus, a 29-fold difference in annualized mortality was observed. In these RCTs, selection for renal disease, defined by either decline in renal function or presence of proteinuria, portends important mortality risk. C1 [Barkoudah, Ebrahim; Skali, Hicham; Solomon, Scott D.; Pfeffer, Marc A.] Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02115 USA. [Barkoudah, Ebrahim] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Uno, Hajime] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Pfeffer, MA (reprint author), Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM mpfeffer@rics.bwh.harvard.edu FU Amgen; Novartis; Sanofi-aventis; Anthera; Boehringer Ingelheim; Boston Scientific; Bristol-Myers Squibb; Cerenis; Eleven Biotherapeutics; GlaxoSmithKline; Hamilton Health Sciences; Karo Bio; Roche; Salutria; Sanofi Aventis; Servier; University of Oxford; Sanofi-Aventis through Brigham and Women's Hospital FX Dr. Pfeffer reports receiving grant support from Amgen, Novartis, and Sanofi-aventis, as well as consulting fees from Amgen, Anthera, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cerenis, Eleven Biotherapeutics, GlaxoSmithKline, Hamilton Health Sciences, Karo Bio, Novartis, Roche, Salutria, Sanofi Aventis, Servier, University of Oxford. Dr Pfeffer is a coinventor on a patent that Brigham and Women's Hospital has for the use of inhibitors of the renin-angiotensin system in selected survivors of MI. His share of the licensing agreements with Novartis and Boehringer, which are irrevocably transferred to charity, are not linked to sales. Dr. Solomon reports receiving research support from Sanofi-Aventis paid through Brigham and Women's Hospital. Drs. Barkoudah, Skali, and Uno report none. NR 43 TC 26 Z9 27 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD FEB PY 2012 VL 1 IS 1 BP 8 EP 15 DI 10.1161/JAHA.111.000059 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 238UM UT WOS:000325976400004 PM 23130114 ER PT J AU Fonarow, GC Saver, JL Smith, EE Broderick, JP Kleindorfer, DO Sacco, RL Pan, WQ Olson, DM Hernandez, AF Peterson, ED Schwamm, LH AF Fonarow, Gregg C. Saver, Jeffrey L. Smith, Eric E. Broderick, Joseph P. Kleindorfer, Dawn O. Sacco, Ralph L. Pan, Wenqin Olson, DaiWai M. Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee H. TI Relationship of National Institutes of Health Stroke Scale to 30-Day Mortality in Medicare Beneficiaries With Acute Ischemic Stroke SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE ischemic stroke; National Institutes of Health Stroke Scale; mortality; registries ID HEART-FAILURE; PREDICTORS; SCORE; OUTCOMES; RELIABILITY; PERFORMANCE; INFARCTION; AGE AB Background-The National Institutes of Health Stroke Scale (NIHSS), a well-validated tool for assessing initial stroke severity, has previously been shown to be associated with mortality in acute ischemic stroke. However, the relationship, optimal categorization, and risk discrimination with the NIHSS for predicting 30-day mortality among Medicare beneficiaries with acute ischemic stroke has not been well studied. Methods and Results-We analyzed data from 33102 fee-for-service Medicare beneficiaries treated at 404 Get With The Guidelines-Stroke hospitals between April 2003 and December 2006 with NIHSS documented. The 30-day mortality rate by NIHSS as a continuous variable and by risk-tree determined or prespecified categories were analyzed, with discrimination of risk quantified by the c-statistic. In this cohort, mean age was 79.0 years and 58% were female. The median NIHSS score was 5 (25th to 75th percentile 2 to 12). There were 4496 deaths in the first 30 days (13.6%). There was a strong graded relation between increasing NIHSS score and higher 30-day mortality. The 30-day mortality rates for acute ischemic stroke by NIHSS categories were as follows: 0 to 7, 4.2%; 8 to 13, 13.9%; 14 to 21, 31.6%; 22 to 42, 53.5%. A model with NIHSS alone provided excellent discrimination whether included as a continuous variable (c-statistic 0.82 [0.81 to 0.83]), 4 categories (c-statistic 0.80 [0.79 to 0.80]), or 3 categories (c-statistic 0.79 [0.78 to 0.79]). Conclusions-The NIHSS provides substantial prognostic information regarding 30-day mortality risk in Medicare beneficiaries with acute ischemic stroke. This index of stroke severity is a very strong discriminator of mortality risk, even in the absence of other clinical information, whether used as a continuous or categorical risk determinant. C1 [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. [Broderick, Joseph P.; Kleindorfer, Dawn O.] Univ Cincinnati, Acad Hlth Ctr, Dept Neurol, Cincinnati, OH 45221 USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA. [Pan, Wenqin; Olson, DaiWai M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Ctr, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. RP Fonarow, GC (reprint author), Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, 10833 LeConte Ave,Room 47-123 CHS, Los Angeles, CA 90095 USA. EM gfonarow@mednet.ucla.edu RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 FU Janssen Pharmaceutical Companies of Johnson Johnson; Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; AHA Pharmaceutical Roundtable FX The Get With The Guidelines (R)-Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. The GWTG-Stroke program is currently supported in part by a charitable contribution from Janssen Pharmaceutical Companies of Johnson & Johnson. GWTG-Stroke has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership and the AHA Pharmaceutical Roundtable. NR 24 TC 50 Z9 53 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD FEB PY 2012 VL 1 IS 1 BP 42 EP 50 DI 10.1161/JAHA.111.000034 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 238UM UT WOS:000325976400007 PM 23130117 ER PT J AU Bolukbasi, MF Mizrak, A Ozdener, GB Madlener, S Strobel, T Erkan, EP Fan, JB Breakefield, XO Saydam, O AF Bolukbasi, Mehmet Fatih Mizrak, Arda Ozdener, Gokhan Baris Madlener, Sibylle Stroebel, Thomas Erkan, Erdogan Pekcan Fan, Jian-Bing Breakefield, Xandra O. Saydam, Okay TI miR-1289 and "Zipcode"-like Sequence Enrich mRNAs in Microvesicles SO MOLECULAR THERAPY-NUCLEIC ACIDS LA English DT Article AB Despite intensive studies, the molecular mechanisms by which the genetic materials are uploaded into microvesicles (MVs) are still unknown. This is the first study describing a zipcode-like 25 nucleotide (nt) sequence in the 3'-untranslated region (3'UTR) of mRNAs, with variants of this sequence present in many mRNAs enriched in MVs, as compared to their glioblastoma cells of origin. When this sequence was incorporated into the 3' UTR of a reporter message and expressed in a different cell type, it led to enrichment of the reporter mRNA in MVs. Critical features of this sequence are both a CUGCC core presented on a stemloop structure and a miRNA-binding site, with increased levels of the corresponding miRNA in cells further increasing levels of mRNAs in MVs. C1 [Bolukbasi, Mehmet Fatih; Mizrak, Arda; Ozdener, Gokhan Baris; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Radiol, Boston, MA USA. [Madlener, Sibylle; Erkan, Erdogan Pekcan; Saydam, Okay] Med Univ Vienna, Dept Pediat, Div Oncol, Mol Neurooncol Res Unit, A-1090 Vienna, Austria. [Stroebel, Thomas] Med Univ Vienna, Inst Neurol, A-1090 Vienna, Austria. [Fan, Jian-Bing] Illumina Inc, San Diego, CA USA. RP Saydam, O (reprint author), Med Univ Vienna, Dept Pediat, Div Oncol, Mol Neurooncol Res Unit, A-1090 Vienna, Austria. EM okay.saydam@meduniwien.ac.at OI Madlener, Sibylle/0000-0001-7099-9997 FU NIH NCI [CA141150]; NIH NINDS [NS037409]; Forschungsgesellschaft for Brain Tumors FX We thank Ms Suzanne McDavitt for skilled editorial assistance, Leonora Balaj for help with RNA work, and Johan Skog for the microarray data presented in Supplementary Table S1. Support for this work was provided by NIH NCI grant CA141150 (X.O.B.), NIH NINDS grant NS037409 (X.O.B. and O.S.), and Forschungsgesellschaft for Brain Tumors (O.S.). The authors declared no competing financial interests. NR 45 TC 64 Z9 66 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2162-2531 J9 MOL THER-NUCL ACIDS JI Mol. Ther.-Nucl. Acids PD FEB PY 2012 VL 1 AR e10 DI 10.1038/mtna.2011.2 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V31HM UT WOS:000208874700003 PM 23344721 ER PT J AU Bichara, DA O'Sullivan, NA Pomerantseva, I Zhao, X Sundback, CA Vacanti, JP Randolph, MA AF Bichara, David A. O'Sullivan, Niamh-Anna Pomerantseva, Irina Zhao, Xing Sundback, Cathryn A. Vacanti, Joseph P. Randolph, Mark A. TI The Tissue-Engineered Auricle: Past, Present, and Future SO TISSUE ENGINEERING PART B-REVIEWS LA English DT Review ID HUMAN SEPTAL CARTILAGE; HUMAN AURICULAR CHONDROCYTES; EAR-SHAPED CARTILAGE; IN-VITRO; ARTICULAR CHONDROCYTES; ALGINATE BEADS; VESICOURETERAL REFLUX; GROWTH-FACTOR; FIBRIN GLUE; POLYMER AB The reconstruction, repair, and regeneration of the external auricular framework continue to be one of the greatest challenges in the field of tissue engineering. To replace like with like, we should emulate the native structure and composition of auricular cartilage by combining a suitable chondrogenic cell source with an appropriate scaffold under optimal in vitro and in vivo conditions. Due to the fact that a suitable and reliable substitute for auricular cartilage has yet to be engineered, hand-carved autologous costal cartilage grafts and ear-shaped porous polyethylene implants are the current treatment modalities for auricular reconstruction. However, over the last decade, significant advances have been made in the field of regenerative medicine and tissue engineering. A variety of scaffolds and innovative approaches have been investigated as alternatives to using autologous carved costal cartilage or porous polyethylene implants. A review of recent developments and the current state of the art and science is presented, focusing on scaffolds, cell sources, seeding densities, and mechanical characteristics of tissue-engineered auricular cartilage. C1 [Bichara, David A.; O'Sullivan, Niamh-Anna; Zhao, Xing; Randolph, Mark A.] Harvard Univ, Plast Surg Res Lab, Div Plast Surg, Med Sch,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pomerantseva, Irina; Sundback, Cathryn A.; Vacanti, Joseph P.; Randolph, Mark A.] Harvard Univ, Dept Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pomerantseva, Irina; Sundback, Cathryn A.; Vacanti, Joseph P.] Harvard Univ, Dept Pediat Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Randolph, MA (reprint author), Harvard Univ, Plast Surg Res Lab, Div Plast Surg, Med Sch,Massachusetts Gen Hosp, Room WAC 435,15 Parkman St, Boston, MA 02114 USA. EM marandolph@partners.org FU Armed Forces Institute of Regenerative Medicine [W81XWH-08-2-0034]; U.S. Army Medical Research Acquisition Activity, Fort Detrick [MD 21702-5014] FX The authors of this study would like to thank illustrator Mariano Recalde for the figure in this article. This research was sponsored by the Armed Forces Institute of Regenerative Medicine award number W81XWH-08-2-0034. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014, is the awarding and administering acquisition office. The content of the article does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. NR 91 TC 46 Z9 48 U1 3 U2 30 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3368 EI 1937-3376 J9 TISSUE ENG PART B-RE JI Tissue Eng. Part B-Rev. PD FEB PY 2012 VL 18 IS 1 BP 51 EP 61 DI 10.1089/ten.teb.2011.0326 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 882ZD UT WOS:000299601500005 PM 21827281 ER PT J AU Watson, RR Brugge, WR AF Watson, Rabindra R. Brugge, William R. TI The role of endoscopy in the management of autoimmune pancreatitis SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material DE autoimmune pancreatitis; cholangiopathy; endoscopic retrograde cholangiopancreatography; endoscopic ultrasound; pancreatic cancer; pancreatitis ID PRIMARY SCLEROSING CHOLANGITIS; INVOLVEMENT; THERAPY; CANCER C1 [Brugge, William R.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. [Watson, Rabindra R.] Univ Calif Los Angeles, David Geffen Sch Med, Med Ctr, Intervent Endoscopy Program, Los Angeles, CA 90095 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. EM wbrugge@partners.org NR 23 TC 0 Z9 0 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4124 J9 EXPERT REV GASTROENT JI Expert Rev. Gastroenterol. Hepatol. PD FEB PY 2012 VL 6 IS 1 BP 5 EP 8 DI 10.1586/EGH.11.73 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 861UO UT WOS:000298045100002 PM 22149574 ER PT J AU Pu, CL Zhou, SY Wang, K Zhang, YF Pei, WJ AF Pu, Cun-Lai Zhou, Si-Yuan Wang, Kai Zhang, Yi-Feng Pei, Wen-Jiang TI Efficient and robust routing on scale-free networks SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article DE Network capacity; Routing; Scale-free networks ID COMPLEX NETWORKS; SMALL-WORLD; NAVIGATION; DYNAMICS AB Information routing is one of the most important problems in large communication networks. In this paper we propose a novel routing strategy in which the optimal paths between all pairs of nodes are chosen according to a cost function that incorporates degrees of nodes in paths. Results on large scale-free networks demonstrate that our routing strategy is more efficient than the shortest path algorithm and the efficient routing strategy proposed by Van et al. [Phys. Rev. E 73, 046108 (2006)]. Furthermore our routing strategy has strong robustness against cascading failure attacks on networks. (C) 2011 Elsevier B.V. All rights reserved. C1 [Pu, Cun-Lai; Zhou, Si-Yuan; Wang, Kai; Zhang, Yi-Feng; Pei, Wen-Jiang] Southeast Univ, Sch Informat Sci & Engn, Nanjing 210096, Jiangsu, Peoples R China. [Pu, Cun-Lai] Northeastern Univ, Dept Phys, Ctr Complex Network Res, Boston, MA 02115 USA. [Pu, Cun-Lai] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Pu, CL (reprint author), Southeast Univ, Sch Informat Sci & Engn, Nanjing 210096, Jiangsu, Peoples R China. EM pucunlai@gmail.com; wjpei@seu.edu.cn FU Natural Science Foundation of China [60672095, 60972165]; National High-Technology Project of China [2007AA11Z210]; Ministry of Education of China [20070286004]; Foundation of High-Technology Project in Jiangsu Province; Natural Science Foundation of Jiangsu Province [BK2008281]; Special Scientific Foundation; National torch plan; Southeast University FX The authors thank Andrew Michaelson, Dr. Chao-Ming Song, Dr. Yang Liu and Dr. Da-Shun Wang for their valuable suggestions. Also the authors would like to thank all the reviewers for their constructive comments that helped us improve this manuscript. This work was supported by the Natural Science Foundation of China under Grant No. 60672095, No. 60972165, the National High-Technology Project of China under Grant No. 2007AA11Z210, the Doctoral Fund of Ministry of Education of China under Grant No. 20070286004, the Foundation of High-Technology Project in Jiangsu Province, the Natural Science Foundation of Jiangsu Province under Grant No. BK2008281, the Special Scientific Foundation for the Eleventh-Five-Year Plan of China, the National torch plan, and the Excellent Young Teachers Program of Southeast University. NR 32 TC 23 Z9 29 U1 0 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD FEB 1 PY 2012 VL 391 IS 3 BP 866 EP 871 DI 10.1016/j.physa.2011.08.044 PG 6 WC Physics, Multidisciplinary SC Physics GA 858EU UT WOS:000297779500047 ER PT J AU Javery, O Jagannathan, JP Saboo, SS Regan, KO Hornick, JL Ramaiya, N AF Javery, Omar Jagannathan, Jyothi P. Saboo, Sachin S. Regan, Kevin O. Hornick, Jason L. Ramaiya, Nikhil TI Atypical lipomatous tumor with unusual extensive metaplastic ossification SO CANCER IMAGING LA English DT Article DE Atypical lipomatous tumor; well-differentiated liposarcoma; metaplastic ossification ID MENINGOTHELIAL-LIKE WHORLS; DEDIFFERENTIATED LIPOSARCOMA; BONE-FORMATION; DIFFERENTIATED LIPOSARCOMA; SOFT-TISSUE; PATTERN; MDM2; CDK4 AB The presence of metaplastic ossification within atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) is a rare occurrence. When present, bone formation is most often found in association with a dedifferentiated component arising within the primary tumor. It is important for the radiologist not only to recognize the differential diagnosis of a calcified or ossified soft tissue mass but also be aware of the various soft tissue neoplasms, both aggressive and non-aggressive, that may show such features. We report a case of ALT/WDLPS with unusual extensive metaplastic bone formation without an element of dedifferentiated liposarcoma. C1 [Jagannathan, Jyothi P.; Saboo, Sachin S.; Regan, Kevin O.; Ramaiya, Nikhil] Harvard Univ, Dept Radiol, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. [Javery, Omar] Harvard Univ, Dept Radiol, Brigham & Womens Hosp, Sch Med, Boston, MA 02215 USA. [Hornick, Jason L.] Harvard Univ, Dept Pathol, Brigham & Womens Hosp, Sch Med, Boston, MA 02215 USA. RP Saboo, SS (reprint author), Harvard Univ, Dept Radiol, Dana Farber Canc Inst, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. EM ssaboo@partners.org NR 18 TC 2 Z9 2 U1 0 U2 0 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 J9 CANCER IMAGING JI Cancer Imaging PD JAN 31 PY 2012 VL 12 IS 1 BP 25 EP 30 DI 10.1102/1470-7330.2012.0004 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 961YZ UT WOS:000305506900001 PM 22375305 ER PT J AU Chiara, DC Dostalova, Z Jayakar, SS Zhou, XJ Miller, KW Cohen, JB AF Chiara, David C. Dostalova, Zuzana Jayakar, Selwyn S. Zhou, Xiaojuan Miller, Keith W. Cohen, Jonathan B. TI Mapping General Anesthetic Binding Site(s) in Human alpha 1 beta 3 gamma-Aminobutyric Acid Type A Receptors with [H-3]TDBzl-Etomidate, a Photoreactive Etomidate SO BIOCHEMISTRY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; GATED ION CHANNELS; GABA(A) RECEPTOR; AMINO-ACID; SUBUNIT; IDENTIFICATION; ANALOG; PHARMACOLOGY; ACTIVATION; INHIBITOR AB The gamma-aminobutyric acid type A receptor (GABAAR) is a target for general anesthetics of diverse chemical structures, which act as positive allosteric modulators at clinical doses. Previously, in a heterogeneous mixture of GABA(A)Rs purified from bovine brain, [H-3]azietomidate photolabeling of alpha Met-236 and beta Met-286 in the alpha M1 and beta M3 transmembrane helices identified an etomidate binding site in the GABA(A)R transmembrane domain at the interface between the beta and alpha subunits [Li, G. D., et.al. (2006) J. Neurosci. 26, 11599-11605]. To further define GABAAR etomidate binding sites, we now use [H-3]TDBzl-etomidate, an aryl diazirine with broader amino acid side chain reactivity than azietornidate, to photolabel purified human FLAG-alpha 1 beta 3 GABA(A)Rs and more extensively identify photolabeled GABA(A)R amino acids. PHYTDBzl-etomidate photolabeled in an etomidate-inhibitable manner beta 3Val-290, in the beta 3M3 transmembrane helix, as well as alpha 1Met-236 in alpha 1M1, a residue photolabeled by [H-3]azietomidate, while no photolabeling of amino acids in the alpha M2 and beta M2 helices that also border the etornidate binding site was detected. The location of these photolabeled amino acids in GABA(A)R homology models derived from the recently determined structures of prokaryote (GLIC) or invertebrate (GluCl) homologues and the results of computational docking studies predict the orientation of [H-3]TDBzl-etomidate bound in that site and the other amino acids contributing to this GABA(A)R intersubunit etomidate binding site. Etomidate-inhibitable photolabeling of beta Met-227 in beta M1 by [H-3]TDBzl-etomidate and [H-3]azietomidate also provides evidence of a homologous etomidate binding site at the beta 3-beta 3 subunit interface in the alpha 1 beta 3 GABA(A)R. C1 [Chiara, David C.; Jayakar, Selwyn S.; Cohen, Jonathan B.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Dostalova, Zuzana; Zhou, Xiaojuan; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Cohen, JB (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM jonathan_cohen@hms.harvard.edu FU National Institutes of Health [GM-58448] FX This research was supported by National Institutes of Health Grant GM-58448. NR 46 TC 50 Z9 51 U1 0 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 31 PY 2012 VL 51 IS 4 BP 836 EP 847 DI 10.1021/bi201772m PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 895CJ UT WOS:000300473500002 PM 22243422 ER PT J AU Bonaca, MP Wiviott, SD Braunwald, E Murphy, SA Ruff, CT Antman, EM Morrow, DA AF Bonaca, Marc P. Wiviott, Stephen D. Braunwald, Eugene Murphy, Sabina A. Ruff, Christian T. Antman, Elliott M. Morrow, David A. TI American College of Cardiology/American Heart Association/European Society of Cardiology/World Heart Federation Universal Definition of Myocardial Infarction Classification System and the Risk of Cardiovascular Death Observations From the TRITON-TIMI 38 Trial (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38) SO CIRCULATION LA English DT Article DE myocardial infarction; mortality; outcomes ID PERCUTANEOUS CORONARY INTERVENTION; CREATINE KINASE-MB; TROPONIN-I ASSAY; ELEVATION; CLOPIDOGREL; MORTALITY; IMPACT; LEVEL; PCI AB Background-The availability of more sensitive biomarkers of myonecrosis and a new classification system from the universal definition of myocardial infarction (MI) have led to evolution of the classification of MI. The prognostic implications of MI defined in the current era have not been well described. Methods and Results-We investigated the association between new or recurrent MI by subtype according to the European Society of Cardiology/American College of Cardiology/American Heart Association/World Health Federation Task Force for the Redefinition of MI Classification System and the risk of cardiovascular death among 13 608 patients with acute coronary syndrome in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38). The adjusted risk of cardiovascular death was evaluated by landmark analysis starting at the time of the MI through 180 days after the event. Patients who experienced an MI during follow-up had a higher risk of cardiovascular death at 6 months than patients without an MI (6.5% versus 1.3%, P<0.001). This higher risk was present across all subtypes of MI, including type 4a (peri-percutaneous coronary intervention, 3.2%; P<0.001) and type 4b (stent thrombosis, 15.4%; P<0.001). After adjustment for important clinical covariates, the occurrence of any MI was associated with a 5-fold higher risk of death at 6 months (95% confidence interval 3.8-7.1), with similarly increased risk across subtypes. Conclusions-MI is associated with a significantly increased risk of cardiovascular death, with a consistent relationship across all types as defined by the universal classification system. These findings underscore the clinical relevance of these events and the importance of therapies aimed at preventing MI. C1 [Bonaca, Marc P.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org FU Abbott Laboratories; Accumetrics; Amgen; AstraZeneca; Beckman Coulter; Bristol-Myers Squibb; CV Therapeutics; Daiichi Sankyo Co Ltd; Eli Lilly and Co; GlaxoSmithKline; Integrated Therapeutics; Merck and Co; Nanosphere; Novartis Pharmaceuticals; Nuvelo; Ortho-Clinical Diagnostics; Pfizer; Roche Diagnostics; sanofi-aventis; Sanofi-Synthelabo; Siemens Medical Solutions; Singulex; Cardiokinetix; Gilead; Instrumentation Laboratory; Ikaria; Merck; Ortho Clinical Diagnostics; Siemens FX The TIMI Study Group has received significant research grant support from Abbott Laboratories, Accumetrics, Amgen, AstraZeneca, Beckman Coulter, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Integrated Therapeutics, Merck and Co, Nanosphere, Novartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, sanofi-aventis, Sanofi-Synthelabo, Siemens Medical Solutions, and Singulex. Dr Wiviott reports receiving consulting fees or paid advisory board fees from sanofi-aventis and lecture fees from Daiichi Sankyo Co Ltd and Eli Lilly and Co. Dr Braunwald reports receiving consulting fees or paid advisory board fees from Daiichi Sankyo Co Ltd and sanofi-aventis and lecture fees from Eli Lilly and Co and sanofi-aventis. Dr Antman has received consulting fees or paid advisory board fees from sanofi-aventis and lecture fees from Eli Lilly and Co and Sanofi-aventis. Dr Morrow has received honoraria for educational presentations from CV Therapeutics and Eli Lilly. He has received consulting fees from Beckman-Coulter, Boehringer Ingelheim, Cardiokinetix, Gilead, Instrumentation Laboratory, Ikaria, Merck, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens and remuneration from AstraZeneca for adjudication as a member of a clinical events committee. The remaining authors report no conflicts. NR 24 TC 80 Z9 87 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 31 PY 2012 VL 125 IS 4 BP 577 EP U90 DI 10.1161/CIRCULATIONAHA.111.041160 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 892ZH UT WOS:000300323900015 PM 22199016 ER PT J AU Hachamovitch, R Nutter, B Hlatky, MA Shaw, LJ Ridner, ML Dorbala, S Beanlands, RSB Chow, BJW Branscomb, E Chareonthaitawee, P Weigold, WG Voros, S Abbara, S Yasuda, T Jacobs, JE Lesser, J Berman, DS Thomson, LEJ Raman, S Heller, GV Schussheim, A Brunken, R Williams, KA Farkas, S Delbeke, D Schoepf, UJ Reichek, N Rabinowitz, S Sigman, SR Patterson, R Corn, CR White, R Kazerooni, E Corbett, J Bokhari, S Machac, J Guarneri, E Borges-Neto, S Millstine, JW Caldwell, J Arrighi, J Hoffmann, U Budoff, M Lima, J Johnson, JR Johnson, B Gaber, M Williams, JA Foster, C Hainer, J Di Carli, MF AF Hachamovitch, Rory Nutter, Benjamin Hlatky, Mark A. Shaw, Leslee J. Ridner, Michael L. Dorbala, Sharmila Beanlands, Rob S. B. Chow, Benjamin J. W. Branscomb, Elizabeth Chareonthaitawee, Panithaya Weigold, W. Guy Voros, Szilard Abbara, Suhny Yasuda, Tsunehiro Jacobs, Jill E. Lesser, John Berman, Daniel S. Thomson, Louise E. J. Raman, Subha Heller, Gary V. Schussheim, Adam Brunken, Richard Williams, Kim A. Farkas, Susan Delbeke, Dominique Schoepf, Uwe J. Reichek, Nathaniel Rabinowitz, Stuart Sigman, Steven R. Patterson, Randall Corn, Carolyn R. White, Richard Kazerooni, Ella Corbett, James Bokhari, Sabahat Machac, Josef Guarneri, Erminia Borges-Neto, Salvador Millstine, John W. Caldwell, James Arrighi, James Hoffmann, Udo Budoff, Matthew Lima, Joao Johnson, James R. Johnson, Barbara Gaber, Mariya Williams, Julie A. Foster, Courtney Hainer, Jon Di Carli, Marcelo F. CA SPARC Investigators TI Patient Management After Noninvasive Cardiac Imaging Results From SPARC (Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in Coronary Artery Disease) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE cardiac; imaging; noninvasive ID EMISSION COMPUTED-TOMOGRAPHY; INCREMENTAL PROGNOSTIC VALUE; RISK STRATIFICATION; CONTROLLED-TRIAL; ANGIOGRAPHY; PREDICTION; THERAPY; IMPACT AB Objectives This study examined short-term cardiac catheterization rates and medication changes after cardiac imaging. Background Noninvasive cardiac imaging is widely used in coronary artery disease, but its effects on subsequent patient management are unclear. Methods We assessed the 90-day post-test rates of catheterization and medication changes in a prospective registry of 1,703 patients without a documented history of coronary artery disease and an intermediate to high likelihood of coronary artery disease undergoing cardiac single-photon emission computed tomography, positron emission tomography, or 64-slice coronary computed tomography angiography. Results Baseline medication use was relatively infrequent. At 90 days, 9.6% of patients underwent catheterization. The rates of catheterization and medication changes increased in proportion to test abnormality findings. Among patients with the most severe test result findings, 38% to 61% were not referred to catheterization, 20% to 30% were not receiving aspirin, 35% to 44% were not receiving a beta-blocker, and 20% to 25% were not receiving a lipid-lowering agent at 90 days after the index test. Risk-adjusted analyses revealed that compared with stress single-photon emission computed tomography or positron emission tomography, changes in aspirin and lipid-lowering agent use was greater after computed tomography angiography, as was the 90-day catheterization referral rate in the setting of normal/nonobstructive and mildly abnormal test results. Conclusions Overall, noninvasive testing had only a modest impact on clinical management of patients referred for clinical testing. Although post-imaging use of cardiac catheterization and medical therapy increased in proportion to the degree of abnormality findings, the frequency of catheterization and medication change suggests possible undertreatment of higher risk patients. Patients were more likely to undergo cardiac catheterization after computed tomography angiography than after single-photon emission computed tomography or positron emission tomography after normal/nonobstructive and mildly abnormal study findings. (Study of Perfusion and Anatomy's Role in Coronary Artery [CAD] [SPARC]; NCT00321399) (J Am Coll Cardiol 2012; 59: 462-74) (C) 2012 by the American College of Cardiology Foundation C1 [Dorbala, Sharmila; Johnson, James R.; Gaber, Mariya; Williams, Julie A.; Foster, Courtney; Hainer, Jon; Di Carli, Marcelo F.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hachamovitch, Rory; Nutter, Benjamin; Brunken, Richard] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Hlatky, Mark A.; Johnson, Barbara] Stanford Univ, Stanford, CA 94305 USA. [Shaw, Leslee J.; Sigman, Steven R.; Patterson, Randall] Emory Univ, Atlanta, GA 30322 USA. [Ridner, Michael L.] Huntsville Dist Mem Hosp, Ctr Heart, Huntsville, AL USA. [Beanlands, Rob S. B.; Chow, Benjamin J. W.] Ottawa Heart Inst, Ottawa, ON, Canada. [Branscomb, Elizabeth] Cardiovasc Associates, Birmingham, AL USA. [Chareonthaitawee, Panithaya] Mayo Clin, Rochester, MN USA. [Weigold, W. Guy] Washington Hosp Ctr, Washington, DC 20010 USA. [Voros, Szilard] Piedmont Heart Inst, Atlanta, GA USA. [Abbara, Suhny; Yasuda, Tsunehiro; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jacobs, Jill E.] NYU Langone Med Ctr, Roslyn, NY USA. [Lesser, John] Minneapolis Heart Inst, Minneapolis, MN USA. [Berman, Daniel S.; Thomson, Louise E. J.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Raman, Subha] Ohio State Univ, Columbus, OH 43210 USA. [Heller, Gary V.] Hartford Hosp, Hartford, CT 06115 USA. [Schussheim, Adam] Cardiac Specialists, Fairfield, CT USA. [Williams, Kim A.] Univ Chicago, Chicago, IL 60637 USA. [Farkas, Susan] Meritcare Heart Ctr, Fargo, ND USA. [Delbeke, Dominique] Vanderbilt Univ, Nashville, TN USA. [Schoepf, Uwe J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Reichek, Nathaniel] St Francis Hosp, Roslyn, NY USA. [Rabinowitz, Stuart] Sinai Hosp, Baltimore, MD 21215 USA. [Corn, Carolyn R.] Oklahoma Heart Hosp, Oklahoma City, OK USA. [White, Richard] Univ Florida, Jacksonville, FL USA. [Kazerooni, Ella; Corbett, James] Univ Michigan, Ann Arbor, MI 48109 USA. [Bokhari, Sabahat] Columbia Univ, New York, NY USA. [Machac, Josef] Mt Sinai Med Ctr, New York, NY 10029 USA. [Guarneri, Erminia] Scripps Clin, La Jolla, CA USA. [Borges-Neto, Salvador] Duke Univ, Durham, NC USA. [Millstine, John W.] Scottsdale Med Imaging, Scottsdale, AZ USA. [Caldwell, James] Univ Washington, Seattle, WA 98195 USA. [Arrighi, James] Rhode Isl Hosp, Providence, RI USA. [Budoff, Matthew] Los Angeles Biomed Res Inst, Torrance, CA USA. [Lima, Joao] Johns Hopkins Univ, Baltimore, MD USA. RP Di Carli, MF (reprint author), Brigham & Womens Hosp, ASB L1 037C,75 Francis St, Boston, MA 02115 USA. EM mdicarli@partners.org OI White, Richard D./0000-0002-1133-7819 FU NHLBI [HL101060-01]; Bracco Diagnostics Inc.; Astellas Pharma US, Inc.; GE Healthcare; Siemens Medical Solutions; Astellas; Siemens; Bracco; Astellas Pharma US Inc.; LMI; GE; Nordion; GE Healthcare, Pfizer; AstraZeneca; Astellas Pharma Inc.; Abbott Vascular; Volcano; Abbott Pharma; Toshiba America Medical Systems; Vital Images; CardioDx; Merck; Cardiogenesis; BD Medical; Bracco Diagnostics; Lantheus; Bayer; Medrad; GE Health; Gilead; Forest Laboratories; GE Medical; Toshiba Medical Imaging FX SPARC is an investigator-initiated study funded in part by a grant from the NHLBI (HL101060-01) and by unrestricted research grants from Bracco Diagnostics Inc.; Astellas Pharma US, Inc.; GE Healthcare; and Siemens Medical Solutions; and unrestricted equipment support for the central imaging analysis from Vital Images. The companies providing unrestricted grants had no access to study data nor had control over any aspect of the study design, data collection, or data analysis. Dr. Hachamovitch has received unrestricted grants from Astellas, Siemens, and Bracco. Dr. Shaw has received grant support from Bracco and Astellas. Dr. Dorbala has received support from Astellas Pharma US Inc. Dr. Beanlands has received research grants from LMI, GE, and Nordion; and is a consultant for LMI and DraxImage. Dr. Chow has received research support from GE Healthcare, Pfizer, and AstraZeneca; eduational support from TeraRecon; and fellowship support from GE Healthcare. Dr. Branscomb is a consultant for Bracco. Dr. Chareonthaitawee has received a research grant from Astellas Pharma Inc. Dr. Voros has received a research grant from Abbott Vascular, Volcano, Abbott Pharma, Toshiba America Medical Systems, Vital Images, CardioDx, Merck, and Cardiogenesis; is a consultant for HDL Inc. and Marquis Imaging; and is on the advisory board and Speaker's Bureau for Merck and Abbott Laboratories. Dr. Abbara has received a research grant from Bracco and BD Medical; and is a consultant for Perceptive Informatics. Dr. Raman has received research support from Siemens. Dr. Heller has received support from Bracco Diagnostics, GE Healthcare, Astellas, and Lantheus. Dr. Williams is on the advisory board and Speaker's Bureau for Astellas Healthcare. Dr. Schoepf is a consultant for and received research support from Bayer, Bracco, GE, Medrad, and Siemens. Dr. Borges-Neto has received grant support and is on the Speaker's Bureau for GE Health, Astellas, and Gilead. Dr. Caldwell has received research support from Forest Laboratories and GE Medical; and is a consultant for Lantheus Imaging. Dr. Arrighi is on the Speaker's Bureau of Astellas Pharma. Dr. Di Carli has received an unrestricted research grant from Astellas, Bracco, Siemens, and GE Healthcare; support from Vital Images; and research grant support from Toshiba Medical Imaging. All other author have reported that they have no relationships relevant to the contents of this paper to disclose. David Cohen, MD, served as Guest Editor for this paper. NR 22 TC 95 Z9 98 U1 1 U2 3 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 JAN 31 PY 2012 VL 59 IS 5 BP 462 EP 474 DI 10.1016/j.jacc.2011.09.066 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 891DD UT WOS:000300195800006 PM 22281249 ER PT J AU Khalili, H Huang, ES Jacobson, BC Camargo, CA Feskanich, D Chan, AT AF Khalili, Hamed Huang, Edward S. Jacobson, Brian C. Camargo, Carlos A., Jr. Feskanich, Diane Chan, Andrew T. TI Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study SO BRITISH MEDICAL JOURNAL LA English DT Article ID INTESTINAL CALCIUM-ABSORPTION; FOOD FREQUENCY QUESTIONNAIRE; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; REPRODUCIBILITY; OMEPRAZOLE; MORTALITY; VALIDITY; SMOKING; METAANALYSIS AB Objective To examine the association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture. Design Prospective cohort study. Setting Nurses' Health Study, which originally recruited from the 11 most populous states in the US. Participants 79 899 postmenopausal women enrolled in the Nurses' Health Study who provided data on the use of PPIs and other risk factors biennially since 2000 and were followed up to 1 June 2008. Main outcome measure Incident hip fracture Results During 565 786 person years of follow-up, we documented 893 incident hip fractures. The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years, compared with 1.51 events per 1000 person years among non-users. Compared with non-users, the risk of hip fracture among women who regularly used PPIs for at least two years was 35% higher (age adjusted hazard ratio 1.35 (95% confidence interval 1.13 to 1.62)), with longer use associated with increasing risk (P-trend<0.01). Adjustment for risk factors, including body mass index, physical activity, and intake of calcium did not materially alter this association (hazard ratio 1.36 (1.13 to 1.63)). These associations were also not changed after accounting for reasons for PPI use. The relation between PPI use and fracture differed by smoking history (P-interaction=0.03). Among current and former smokers, PPI use was associated with greater than 50% increase in risk of fracture, with a multivariate hazard ratio for fracture of 1.51 (1.20 to 1.91). In contrast, among women who never smoked there was no association (multivariate hazard ratio 1.06 (0.77 to 1.46)). In a meta-analysis of these results with 10 prior studies, the pooled odds ratio of hip fracture associated with PPI use was 1.30 (1.25 to 1.36). Conclusion Chronic use of PPIs is associated with increased risk of hip fracture, particularly among women with a history of smoking. C1 [Khalili, Hamed; Huang, Edward S.; Chan, Andrew T.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. [Jacobson, Brian C.] Boston Univ, Med Ctr, Sect Gastroenterol, Boston, MA 02118 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.; Feskanich, Diane; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Camargo, Carlos A., Jr.; Feskanich, Diane; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastroenterol Unit, 55 Fruit St,GRJ 728A, Boston, MA 02114 USA. EM achan@partners.org OI Jacobson, Brian/0000-0001-7064-2357 FU US National Institutes of Health [NIH R01 CA137178, P01 CA87969]; National Institutes of Health (NIH) [R01 DK088782]; IBD Working Group; American Gastroenterological Association FX This study was funded by the US National Institutes of Health (grant No NIH R01 CA137178, P01 CA87969). ATC is a Damon Runyon Cancer Research Foundation clinical investigator. BCJ is supported by a grant from the National Institutes of Health (NIH R01 DK088782). HK is supported by a career development award from the IBD Working Group. ESH is supported by a career development award from the American Gastroenterological Association. NR 43 TC 70 Z9 78 U1 0 U2 8 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD JAN 31 PY 2012 VL 344 AR e372 DI 10.1136/bmj.e372 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 889QI UT WOS:000300087900003 PM 22294756 ER PT J AU Haining, WN AF Haining, W. Nicholas TI Travels in time: Assessing the functional complexity of T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID MEMORY; EFFECTOR; VACCINE; DIFFERENTIATION; PROTECTION C1 [Haining, W. Nicholas] Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Haining, W. Nicholas] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. RP Haining, WN (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. EM nicholas_haining@dfci.harvard.edu FU NIAID NIH HHS [R01 AI091493] NR 15 TC 1 Z9 1 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 JAN 31 PY 2012 VL 109 IS 5 BP 1359 EP 1360 DI 10.1073/pnas.1119856109 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 884TJ UT WOS:000299731400015 PM 22307586 ER PT J AU Jang, E Albadawi, H Watkins, MT Edelman, ER Baker, AB AF Jang, Eugene Albadawi, Hassan Watkins, Michael T. Edelman, Elazer R. Baker, Aaron B. TI Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE heparan sulfate; proteoglycan; arteriogenesis; growth factor trafficking ID FACTOR FGF RECEPTOR-1; HEPARAN-SULFATE; CELLS; TRIAL; DIFFERENTIATION; ACTIVATION; EXPRESSION; THERAPY AB Ischemia of the myocardium and lower limbs is a common consequence of arterial disease and a major source of morbidity and mortality in modernized countries. Inducing neovascularization for the treatment of ischemia is an appealing therapeutic strategy for patients for whom traditional treatment modalities cannot be performed or are ineffective. In the past, the stimulation of blood vessel growth was pursued using direct delivery of growth factors, angiogenic gene therapy, or cellular therapy. Although therapeutic angiogenesis holds great promise for treating patients with ischemia, current methods have not found success in clinical trials. Fibroblast growth factor-2 (FGF-2) was one of the first growth factors to be tested for use in therapeutic angiogenesis. Here, we present a method for improving the biological activity of FGF-2 by codelivering the growth factor with a liposomally embedded coreceptor, syndecan-4. This technique was shown to increase FGF-2 cellular signaling, uptake, and nuclear localization in comparison with FGF-2 alone. Delivery of syndecan-4 proteoliposomes also increased endothelial proliferation, migration, and angiogenic tube formation in response to FGF-2. Using an animal model of limb ischemia, syndecan-4 proteoliposomes markedly improved the neovascularization following femoral artery ligation and recovery of perfusion of the ischemic limb. Taken together, these results support liposomal delivery of syndecan-4 as an effective means to improving the potential of using growth factors to achieve therapeutic neovascularization of ischemic tissue. C1 [Baker, Aaron B.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Jang, Eugene; Edelman, Elazer R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Albadawi, Hassan; Watkins, Michael T.] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Albadawi, Hassan; Watkins, Michael T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Baker, AB (reprint author), Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. EM abbaker1@gmail.com OI Jang, Eugene/0000-0002-9808-2678 FU American Heart Association [10SDG2630139] FX This work was supported by Philip Morris International through a postdoctoral research fellowship and Scientist Development Grant 10SDG2630139 from the American Heart Association (to A.B.B.). NR 28 TC 16 Z9 18 U1 0 U2 8 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 JAN 31 PY 2012 VL 109 IS 5 BP 1679 EP 1684 DI 10.1073/pnas.1117885109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 884TJ UT WOS:000299731400067 PM 22307630 ER PT J AU Peyrache, A Dehghani, N Eskandar, EN Madsen, JR Anderson, WS Donoghue, JA Hochberg, LR Halgren, E Cash, SS Destexhe, A AF Peyrache, Adrien Dehghani, Nima Eskandar, Emad N. Madsen, Joseph R. Anderson, William S. Donoghue, Jacob A. Hochberg, Leigh R. Halgren, Eric Cash, Sydney S. Destexhe, Alain TI Spatiotemporal dynamics of neocortical excitation and inhibition during human sleep SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE spontaneous activity; ensemble recordings; single unit; functional dynamics ID IN-VIVO; CORTICAL NETWORKS; CEREBRAL-CORTEX; SINGLE-NEURON; INTERNEURONS; OSCILLATIONS; DISCHARGES; RECORDINGS; EPILEPSY; STATES AB Intracranial recording is an important diagnostic method routinely used in a number of neurological monitoring scenarios. In recent years, advancements in such recordings have been extended to include unit activity of an ensemble of neurons. However, a detailed functional characterization of excitatory and inhibitory cells has not been attempted in human neocortex, particularly during the sleep state. Here, we report that such feature discrimination is possible from high-density recordings in the neocortex by using 2D multielectrode arrays. Successful separation of regular-spiking neurons (or bursting cells) from fast-spiking cells resulted in well-defined clusters that each showed unique intrinsic firing properties. The high density of the array, which allowed recording from a large number of cells (up to 90), helped us to identify apparent monosynaptic connections, confirming the excitatory and inhibitory nature of regular-spiking and fast-spiking cells, thus categorized as putative pyramidal cells and interneurons, respectively. Finally, we investigated the dynamics of correlations within each class. A marked exponential decay with distance was observed in the case of excitatory but not for inhibitory cells. Although the amplitude of that decline depended on the time-scale at which the correlations were computed, the spatial constant did not. Furthermore, this spatial constant is compatible with the typical size of human columnar organization. These findings provide a detailed characterization of neuronal activity, functional connectivity at the microcircuit level, and the interplay of excitation and inhibition in the human neocortex. C1 [Donoghue, Jacob A.; Hochberg, Leigh R.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eskandar, Emad N.; Donoghue, Jacob A.; Hochberg, Leigh R.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Peyrache, Adrien; Dehghani, Nima; Destexhe, Alain] Ctr Natl Rech Sci, Unit Neurosci Informat & Complexite, F-91198 Gif Sur Yvette, France. [Peyrache, Adrien] Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Nayef Al Rodhan Labs Cellular Neurosurg & Neurosu, Boston, MA 02114 USA. [Madsen, Joseph R.] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Madsen, Joseph R.; Anderson, William S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Madsen, Joseph R.; Anderson, William S.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Hochberg, Leigh R.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Hochberg, Leigh R.] Dept Vet Affairs, Rehabil Res & Dev Serv, Providence, RI 02908 USA. [Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Halgren, Eric] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92037 USA. [Halgren, Eric] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92037 USA. [Halgren, Eric] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92037 USA. RP Cash, SS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM scash@partners.org; destexhe@unic.cnrs-gif.fr OI Dehghani, Nima/0000-0003-2032-8903; Destexhe, Alain/0000-0001-7405-0455 FU Centre National de la Recherche Scientifique; Agence Nationale de la Recherche; European Community [FP6-015879]; BrainScaleS (Brain-Inspired Multiscale Computation in Neuromorphic Hybrid Systems) [FP7-269921]; National Institutes of Health [5R01NS062092, R01 EB009282] FX This research was supported by the Centre National de la Recherche Scientifique, Agence Nationale de la Recherche HR-Cortex project, European Community Future and Emerging Technologies program Fast Analog Computing with Emergent Transient States (FACETS) Grant FP6-015879 and BrainScaleS (Brain-Inspired Multiscale Computation in Neuromorphic Hybrid Systems) Grant FP7-269921, and National Institutes of Health Grants 5R01NS062092 and R01 EB009282. N.D. is supported by a fellowship from Ecole des Neurosciences de Paris, and A.P. is supported by a postdoctoral fellowship from the European Molecular Biology Organization. NR 40 TC 34 Z9 34 U1 2 U2 6 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 JAN 31 PY 2012 VL 109 IS 5 BP 1731 EP 1736 DI 10.1073/pnas.1109895109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 884TJ UT WOS:000299731400076 PM 22307639 ER PT J AU Wucherpfennig, K AF Wucherpfennig, Kai TI Role of Disorder in T-Cell Signaling SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 56th Annual Meeting of the Biophysical-Society CY FEB 25-29, 2012 CL San Diego, CA SP Biophys Soc C1 [Wucherpfennig, Kai] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 31 PY 2012 VL 102 IS 3 SU 1 BP 2A EP 2A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200009 ER PT J AU Golenar, T Csordas, G Perocchi, F Mootha, VK Hajnoczky, G AF Golenar, Tunde Csordas, Gyorgy Perocchi, Fabiana Mootha, Vamsi K. Hajnoczky, Gyorgy TI Dichotomy between Mitochondrial Ca2+Uptake and Martix [Ca2+] in MICU1 Deficient Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 56th Annual Meeting of the Biophysical-Society CY FEB 25-29, 2012 CL San Diego, CA SP Biophys Soc C1 [Golenar, Tunde; Csordas, Gyorgy; Hajnoczky, Gyorgy] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Perocchi, Fabiana; Mootha, Vamsi K.] Harvard Univ, Sch Med, Boston, MA USA. [Perocchi, Fabiana; Mootha, Vamsi K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 31 PY 2012 VL 102 IS 3 SU 1 BP 163A EP 163A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201113 ER PT J AU Halvorsen, K Wong, WP AF Halvorsen, Ken Wong, Wesley P. TI Self-Assembly of a DNA-Based Switchable Linker for Single-Molecule Force Spectroscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 56th Annual Meeting of the Biophysical-Society CY FEB 25-29, 2012 CL San Diego, CA SP Biophys Soc C1 [Halvorsen, Ken; Wong, Wesley P.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Halvorsen, Ken; Wong, Wesley P.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 31 PY 2012 VL 102 IS 3 SU 1 BP 181A EP 181A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201203 ER PT J AU Quintana, A Sharma, S Findlay, GM Baust, B Jain, M Nilsson, R Mettlen, M Hogan, P Rao, A AF Quintana, Ariel Sharma, Sonia Findlay, Gregory M. Baust, Beate Jain, Mohit Nilsson, Roland Mettlen, Marcel Hogan, Patrick Rao, Anjana TI Novel Modulators of STIM-ORAI Calcium Entry Pathway SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 56th Annual Meeting of the Biophysical-Society CY FEB 25-29, 2012 CL San Diego, CA SP Biophys Soc C1 [Quintana, Ariel; Sharma, Sonia; Findlay, Gregory M.; Hogan, Patrick; Rao, Anjana] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. [Baust, Beate] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA USA. [Jain, Mohit] Broad Inst, Cambridge, MA USA. [Jain, Mohit] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Nilsson, Roland] Karolinska Inst, Stockholm, Sweden. [Mettlen, Marcel] Scripps Res Inst, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 31 PY 2012 VL 102 IS 3 SU 1 BP 314A EP 314A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202178 ER PT J AU Sovari, AA Jeong, EM Arasu, D Rutledge, CA Dolmatova, E Vahdani, N Gu, LZ Duffy, H Bonini, MG Dudley, SC AF Sovari, Ali A. Jeong, Euy-Myoung Arasu, Divya Rutledge, Cody A. Dolmatova, Elena Vahdani, Nooshin Gu, Lianzhe Duffy, Heather Bonini, Marcelo G. Dudley, Samuel C. TI Mitochondrial Oxidative Stress Mediates the Effect of Angiotensin II on Gap Junctional Remodeling and Sudden Arrhythmic Death SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 56th Annual Meeting of the Biophysical-Society CY FEB 25-29, 2012 CL San Diego, CA SP Biophys Soc C1 [Sovari, Ali A.; Jeong, Euy-Myoung; Arasu, Divya; Rutledge, Cody A.; Vahdani, Nooshin; Gu, Lianzhe; Bonini, Marcelo G.; Dudley, Samuel C.] UIC, Chicago, IL USA. [Dolmatova, Elena; Duffy, Heather] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 31 PY 2012 VL 102 IS 3 SU 1 BP 341A EP 341A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202307 ER PT J AU Wong, WP AF Wong, Wesley P. TI Mechanoregulation in Nanoscale Biology: From Hemostasis to Single-Molecule Centrifugation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 56th Annual Meeting of the Biophysical-Society CY FEB 25-29, 2012 CL San Diego, CA SP Biophys Soc C1 [Wong, Wesley P.] Harvard Univ, Rowland Inst Harvard, Cambridge, MA 02138 USA. [Wong, Wesley P.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Wong, Wesley P.] Childrens Hosp, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 31 PY 2012 VL 102 IS 3 SU 1 BP 407A EP 407A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202647 ER PT J AU Reznichenko, L Cheng, Q Nizar, K Gratiy, SL Saisan, PA Rockenstein, EM Gonzalez, T Patrick, C Spencer, B Desplats, P Dale, AM Devor, A Masliah, E AF Reznichenko, Lidia Cheng, Qun Nizar, Kristal Gratiy, Sergey L. Saisan, Payam A. Rockenstein, Edward M. Gonzalez, Tanya Patrick, Cristina Spencer, Brian Desplats, Paula Dale, Anders M. Devor, Anna Masliah, Eliezer TI Increased Calcium Influx and Decreased Buffering Capacity of Intracellular Stores Underlie Neuropathology Induced by Over-Expression of alpha-Synuclein SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 56th Annual Meeting of the Biophysical-Society CY FEB 25-29, 2012 CL San Diego, CA SP Biophys Soc C1 [Reznichenko, Lidia; Cheng, Qun; Nizar, Kristal; Gratiy, Sergey L.; Saisan, Payam A.; Rockenstein, Edward M.; Gonzalez, Tanya; Patrick, Cristina; Spencer, Brian; Desplats, Paula; Dale, Anders M.; Devor, Anna; Masliah, Eliezer] UCSD, La Jolla, CA USA. [Devor, Anna] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 31 PY 2012 VL 102 IS 3 SU 1 BP 424A EP 425A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203024 ER PT J AU Yang, DR Feldman, T Cheng, D Halvorsen, K Wong, WP AF Yang, Darren Feldman, Theodore Cheng, Daniel Halvorsen, Ken Wong, Wesley P. TI Single-Molecule Investigations of Von Willebrand Factor in Hydrodynamic Flow SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 56th Annual Meeting of the Biophysical-Society CY FEB 25-29, 2012 CL San Diego, CA SP Biophys Soc C1 [Yang, Darren; Feldman, Theodore; Cheng, Daniel; Halvorsen, Ken; Wong, Wesley P.] Harvard Univ, Cambridge, MA 02138 USA. [Yang, Darren; Feldman, Theodore] Sch Engn & Appl Sci, Cambridge, MA USA. [Cheng, Daniel; Halvorsen, Ken; Wong, Wesley P.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 31 PY 2012 VL 102 IS 3 SU 1 BP 578A EP 578A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204098 ER PT J AU Ye, CP Kong, D Koda, S Krashes, M Lowell, BB AF Ye, Chianping Kong, Dong Koda, Shuichi Krashes, Mike Lowell, Bradford B. TI Optical Activation or Silencing of Neural Activaty in Neurons that Regulate Energy Balance in the Hypothalamus SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 56th Annual Meeting of the Biophysical-Society CY FEB 25-29, 2012 CL San Diego, CA SP Biophys Soc C1 [Ye, Chianping; Kong, Dong; Krashes, Mike; Lowell, Bradford B.] BIDMC, Boston, MA USA. [Ye, Chianping; Kong, Dong; Krashes, Mike; Lowell, Bradford B.] Harvard Univ, Sch Med, Boston, MA USA. [Koda, Shuichi] AsubioPhama, Kobe, Hyogo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 31 PY 2012 VL 102 IS 3 SU 1 BP 670A EP 671A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204569 ER PT J AU Masia, R Yellen, G AF Masia, Ricard Yellen, Gary TI Outwardly Rectifying Currents in Hepatocytes are Inhibited by 2-APB SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 56th Annual Meeting of the Biophysical-Society CY FEB 25-29, 2012 CL San Diego, CA SP Biophys Soc C1 [Masia, Ricard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yellen, Gary] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 31 PY 2012 VL 102 IS 3 SU 1 BP 680A EP 680A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204613 ER PT J AU Huang, JH Al-Mozaini, M Rogich, J Carrington, MF Seiss, K Pereyra, F Lichterfeld, M Yu, XG AF Huang, Jinghe Al-Mozaini, Maha Rogich, Jerome Carrington, Mary F. Seiss, Katherine Pereyra, Florencia Lichterfeld, Mathias Yu, Xu G. TI Systemic inhibition of myeloid dendritic cells by circulating HLA class I molecules in HIV-1 infection SO RETROVIROLOGY LA English DT Article DE HIV-1; dendritic cells; HLA; immunoregulation; Leukocyte Immunoglobulin Like Receptor (LILR) ID DISEASE PROGRESSION; UP-REGULATION; ANTIGENS; RECEPTORS; APOPTOSIS; SERUM; DETERMINANTS; DYSFUNCTION; ENGAGEMENT; ILT4 AB Background: HIV-1 infection is associated with profound dysfunction of myeloid dendritic cells, for reasons that remain ill-defined. Soluble HLA class I molecules can have important inhibitory effects on T cells and NK cells, but may also contribute to reduced functional properties of professional antigen-presenting cells. Here, we investigated the expression of soluble HLA class I isoforms during HIV-1 infection and assessed their functional impact on antigen-presenting characteristics of dendritic cells. Results: Soluble HLA class I molecules were highly upregulated in progressive HIV-1 infection as determined by quantitative Western blots. This was associated with strong increases of intracellular expression of HLA class I isoforms in dendritic cells and monocytes. Using mixed lymphocyte reactions, we found that soluble HLA class I molecules effectively inhibited the antigen-presenting properties of dendritic cells, however, there was no significant influence of HLA class I molecules on the cytokine-secretion properties of these cells. The immunomodulatory effects of soluble HLA class I molecules were mediated by interactions with inhibitory myelomonocytic MHC class I receptors from the Leukocyte Immunoglobulin Like Receptor (LILR) family. Conclusions: During progressive HIV-1 infection, soluble HLA class I molecules can contribute to systemic immune dysfunction by inhibiting the antigen-presenting properties of myeloid dendritic cells through interactions with inhibitory myelomonocytic HLA class I receptors. C1 [Huang, Jinghe; Al-Mozaini, Maha; Rogich, Jerome; Carrington, Mary F.; Seiss, Katherine; Pereyra, Florencia; Yu, Xu G.] Ragon Inst MIT MGH & Harvard, Boston, MA USA. [Al-Mozaini, Maha] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Al-Mozaini, Maha] King Faisal Specialist Hosp & Res Ctr, Riyadh, Saudi Arabia. RP Yu, XG (reprint author), Ragon Inst MIT MGH & Harvard, Boston, MA USA. EM xyu@partners.org RI Huang, Jinghe/O-1986-2015 FU National Institutes of Health of the US [AI078799]; Dubai Harvard Foundation for Medical Research; Doris Duke Charitable Foundation [2009034] FX This work was supported by the National Institutes of Health of the US (AI078799 and ARRA supplement to AI078799 to XGY). MAM is the recipient of a fellowship award from the Dubai Harvard Foundation for Medical Research. ML and XGY are both recipients of the Clinical Scientist Development Award from the Doris Duke Charitable Foundation. This work was supported by the Doris Duke Charitable Foundation Grant # 2009034. NR 28 TC 3 Z9 3 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JAN 30 PY 2012 VL 9 AR 11 DI 10.1186/1742-4690-9-11 PG 8 WC Virology SC Virology GA 911LY UT WOS:000301719500001 PM 22289474 ER PT J AU Srinivasan, VJ Radhakrishnan, H Jiang, JY Barry, S Cable, AE AF Srinivasan, Vivek J. Radhakrishnan, Harsha Jiang, James Y. Barry, Scott Cable, Alex E. TI Optical coherence microscopy for deep tissue imaging of the cerebral cortex with intrinsic contrast SO OPTICS EXPRESS LA English DT Article ID RAT HIPPOCAMPAL SLICES; IN-VIVO; SPREADING DEPRESSION; ULTRAHIGH-RESOLUTION; 2-PHOTON MICROSCOPY; SCATTERING MEDIA; REFRACTIVE-INDEX; LIGHT-SCATTERING; BRAIN-TISSUE; BLOOD-FLOW AB In vivo optical microscopic imaging techniques have recently emerged as important tools for the study of neurobiological development and pathophysiology. In particular, two-photon microscopy has proved to be a robust and highly flexible method for in vivo imaging in highly scattering tissue. However, two-photon imaging typically requires extrinsic dyes or contrast agents, and imaging depths are limited to a few hundred microns. Here we demonstrate Optical Coherence Microscopy (OCM) for in vivo imaging of neuronal cell bodies and cortical myelination up to depths of similar to 1.3 mm in the rat neocortex. Imaging does not require the administration of exogenous dyes or contrast agents, and is achieved through intrinsic scattering contrast and image processing alone. Furthermore, using OCM we demonstrate in vivo, quantitative measurements of optical properties (index of refraction and attenuation coefficient) in the cortex, and correlate these properties with laminar cellular architecture determined from the images. Lastly, we show that OCM enables direct visualization of cellular changes during cell depolarization and may therefore provide novel optical markers of cell viability. (C) 2012 Optical Society of America C1 [Srinivasan, Vivek J.] Harvard Univ, Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. [Radhakrishnan, Harsha] Penn State Univ, Ctr Neural Engn, University Pk, PA 16802 USA. [Jiang, James Y.; Barry, Scott; Cable, Alex E.] Thorlabs Inc, Adv Imaging Grp, Newton, NJ 07860 USA. RP Srinivasan, VJ (reprint author), Harvard Univ, Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. EM vjsriniv@nmr.mgh.harvard.edu RI Radhakrishnan, Harsha/K-5557-2012 FU National Institutes of Health [K99NS067050, EB001954 R01]; American Heart Association [11IRG5440002]; Glaucoma Research Foundation Catalyst for a Cure 2 FX We acknowledge helpful suggestions or references from James Fujimoto, Bruce Rosen, Jeff Lichtman, Cenk Ayata, Eng Lo, Jean Augustinack, David Boas, Anna Devor, Sava Sakadzic, Mohammed Abbas Yaseen, and Maria Angela Franceschini. We thank Maria Angela Franceschini for permission to use the OCT microscope. We thank Weicheng Wu for the rat surgery. We acknowledge support from the National Institutes of Health (K99NS067050, EB001954 R01), the American Heart Association (11IRG5440002), and the Glaucoma Research Foundation Catalyst for a Cure 2. NR 43 TC 48 Z9 48 U1 1 U2 26 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 JAN 30 PY 2012 VL 20 IS 3 BP 2220 EP 2239 DI 10.1364/OE.20.002220 PG 20 WC Optics SC Optics GA 895ME UT WOS:000300499500031 PM 22330462 ER PT J AU Halpern, SD Asch, DA Volpp, KG AF Halpern, Scott D. Asch, David A. Volpp, Kevin G. TI Commitment contracts as a way to health SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID SELF-CONTROL C1 [Halpern, Scott D.; Asch, David A.; Volpp, Kevin G.] Univ Penn, Ctr Hlth Incent & Behav Econ, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Halpern, Scott D.; Asch, David A.; Volpp, Kevin G.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Halpern, Scott D.; Asch, David A.] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, VA Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. RP Halpern, SD (reprint author), Univ Penn, Ctr Hlth Incent & Behav Econ, Leonard Davis Inst Hlth Econ, 423 Guardian Dr, Philadelphia, PA 19104 USA. EM shalpern@exchange.upenn.edu OI Asch, David/0000-0002-7970-286X FU NCI NIH HHS [R01 CA159932]; NIA NIH HHS [RC2 AG036592] NR 11 TC 13 Z9 13 U1 1 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD JAN 30 PY 2012 VL 344 AR e522 DI 10.1136/bmj.e522 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 889QD UT WOS:000300087400004 PM 22290100 ER PT J AU Ramos-Casals, M Stone, JH Cid, MC Bosch, X AF Ramos-Casals, Manuel Stone, John H. Cid, Maria C. Bosch, Xavier TI The cryoglobulinaemias SO LANCET LA English DT Article ID HEPATITIS-C VIRUS; II MIXED CRYOGLOBULINEMIA; MONOCLONAL-ANTIBODY TREATMENT; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; CHRONIC HCV INFECTION; B-CELL-PROLIFERATION; LONG-TERM; INTERFERON-ALPHA; PERIPHERAL NEUROPATHY AB Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures less than 37 degrees C and produce organ damage through two main pathways: vascular sludging (hyperviscosity syndrome, mainly in type I cryoglobulinaemia) and immune-mediated mechanisms (principally vasculitis, in mixed cryoglobulinaemia). Cryoglobulinaemia is associated with many illnesses, which can be broadly grouped into infections, autoimmune disorders, and malignancies; the most common cause is infection with hepatitis C virus. Mixed cryoglobulinaemic syndrome is diagnosed when a patient has typical organ involvement (mainly skin, kidney, or peripheral nerve) and circulating cryoglobulins. Cutaneous purpura is the most common manifestation of cryoglobulinaemic vasculitis. The most frequently affected internal organs are the peripheral nerves, kidneys, and joints. The course varies widely and prognosis is influenced by both cryoglobulinaemic damage to vital organs and by comorbidities associated with underlying diseases. More than 90% of cases of cryoglobulinaemia have a known underlying cause; therefore treatment is focused on the cause of the disorder rather than merely symptomatic relief. Studies suggest that both combined or sequential antiviral therapies and targeted biological treatments might be more effective than monotherapy. C1 [Bosch, Xavier] Univ Barcelona, Inst Invest Biomed August Pi & Sunyer, Hosp Clin, Dept Internal Med,Inst Clin Med Dermatol 1, E-08036 Barcelona, Spain. [Ramos-Casals, Manuel] Univ Barcelona, Inst Invest Biomed August Pi & Sunyer, Josep Font Lab Autoimmune Dis, Hosp Clin,Inst Clin Med Dermatol 1, E-08036 Barcelona, Spain. [Cid, Maria C.] Univ Barcelona, Inst Invest Biomed August Pi & Sunyer, Dept Autoimmune Dis, Vasculitis Res Unit,Hosp Clin,Inst Clin Med Derma, E-08036 Barcelona, Spain. [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Bosch, X (reprint author), Univ Barcelona, Inst Invest Biomed August Pi & Sunyer, Hosp Clin, Dept Internal Med,Inst Clin Med Dermatol 1, E-08036 Barcelona, Spain. EM xavbosch@clinic.ub.es OI Ramos-Casals, Manuel/0000-0001-5709-6734; Cid Xutgla, Maria Cinta/0000-0002-4730-0938 FU Centocor; Bristol-Myers Squibb; Roche; Genentech FX MCC has received consultancy fees, research grants and speaker's fees from Centocor; and speaker's fees from Bristol-Myers Squibb and Roche. JS has received consultancy fees from Genentech. XB and MR-C declare that they have no conflicts of interest. NR 141 TC 110 Z9 122 U1 3 U2 10 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 JAN 28 PY 2012 VL 379 IS 9813 BP 348 EP 360 DI 10.1016/S0140-6736(11)60242-0 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 889BA UT WOS:000300047300042 PM 21868085 ER PT J AU Fitzgerald, JP Nayak, B Shanmugasundaram, K Friedrichs, W Sudarshan, S Eid, AA DeNapoli, T Parekh, DJ Gorin, Y Block, K AF Fitzgerald, John P. Nayak, Bijaya Shanmugasundaram, Karthigayan Friedrichs, William Sudarshan, Sunil Eid, Assaad A. DeNapoli, Thomas Parekh, Dipen J. Gorin, Yves Block, Karen TI Nox4 Mediates Renal Cell Carcinoma Cell Invasion through Hypoxia-Induced Interleukin 6-and 8-Production SO PLOS ONE LA English DT Article ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; OXIDASE SUBUNIT NOX4; INDUCIBLE FACTOR-I; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; NAD(P)H OXIDASE; ACTIVATION; EXPRESSION; INFLAMMATION AB Background: Inflammatory cytokines are detected in the plasma of patients with renal cell carcinoma (RCC) and are associated with poor prognosis. However, the primary cell type involved in producing inflammatory cytokines and the biological significance in RCC remain unknown. Inflammation is associated with oxidative stress, upregulation of hypoxia inducible factor 1-alpha, and production of pro-inflammatory gene products. Solid tumors are often heterogeneous in oxygen tension together suggesting that hypoxia may play a role in inflammatory processes in RCC. Epithelial cells have been implicated in cytokine release, although the stimuli to release and molecular mechanisms by which they are released remain unclear. AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status and a role for AMPK in the regulation of cell inflammatory processes has recently been demonstrated. Methods and Principal Findings: We have identified for the first time that interleukin-6 and interleukin-8 (IL-6 and IL-8) are secreted solely from RCC cells exposed to hypoxia. Furthermore, we demonstrate that the NADPH oxidase isoform, Nox4, play a key role in hypoxia-induced IL-6 and IL-8 production in RCC. Finally, we have characterized that enhanced levels of IL-6 and IL-8 result in RCC cell invasion and that activation of AMPK reduces Nox4 expression, IL-6 and IL-8 production, and RCC cell invasion. Conclusions/Significance: Together, our data identify novel mechanisms by which AMPK and Nox4 may be linked to inflammation-induced RCC metastasis and that pharmacological activation of AMPK and/or antioxidants targeting Nox4 may represent a relevant therapeutic intervention to reduce IL-6- and IL-8-induced inflammation and cell invasion in RCC. C1 [Fitzgerald, John P.; Shanmugasundaram, Karthigayan; Sudarshan, Sunil; Parekh, Dipen J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Block, Karen] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX 78229 USA. [Nayak, Bijaya; Eid, Assaad A.; Gorin, Yves; Block, Karen] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [DeNapoli, Thomas] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Fitzgerald, JP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. EM block@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925 FU Veterans Administration Research Service; National Institutes of Health, National Cancer Institute (NCI) [R01:CA131272, K08:CA138774]; Cancer Center Support Grant, National Cancer Institute [5 P30 CA054174-18] FX This work was supported by the Veterans Administration Research Service, Career Scientist Award (KB) and the National Institutes of Health, National Cancer Institute (NCI) grants R01:CA131272 (KB) and K08:CA138774 (SS). This work was also supported in part by the Cancer Center Support Grant, National Cancer Institute, 5 P30 CA054174-18 (DJP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 34 Z9 35 U1 1 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 JAN 27 PY 2012 VL 7 IS 1 AR e30712 DI 10.1371/journal.pone.0030712 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 911GB UT WOS:000301704200030 PM 22303451 ER PT J AU Sun, Q Prasad, R Rosenthal, E Katiyar, SK AF Sun, Qian Prasad, Ram Rosenthal, Eben Katiyar, Santosh K. TI Grape Seed Proanthocyanidins Inhibit the Invasiveness of Human HNSCC Cells by Targeting EGFR and Reversing the Epithelial-To-Mesenchymal Transition SO PLOS ONE LA English DT Article ID NF-KAPPA-B; FACTOR BINDING PROTEIN-3; GROWTH-FACTOR RECEPTOR; NECK-CANCER; MOUSE SKIN; E-CADHERIN; CARCINOMA; HEAD; SURVIVAL; FLUOROURACIL AB Head and neck squamous cell carcinoma (HNSCC) is responsible for approximately 20,000 deaths per year in the United States. Most of the deaths are due to the metastases. To develop more effective strategies for the prevention of metastasis of HNSCC cells, we have determined the effect of grape seed proanthocyanidins (GSPs) on the invasive potential of HNSCC cell and the mechanisms underlying these effects using OSC19 cells as an in vitro model. Using cell invasion assays, we established that treatment of the OSC19 cells with GSPs resulted in a dose-dependent inhibition of cell invasion. EGFR is over-expressed in 90% of HNSCCs and the EGFR inhibitors, erlotinib and gefitinib, are being explored as therapies for this disease. We found that GSPs treatment reduced the levels of expression of EGFR in the OSC19 cells as well as reducing the activation of NF-kappa B/p65, a downstream target of EGFR, and the expression of NF-kappa B-responsive proteins. GSPs treatment also reduced the activity of ERK1/2, an upstream regulator of NF-kappa B and treatment of the cells with caffeic acid phenethyl ester, an inhibitor of NF-kappa B, inhibited cell invasion. Overexpression of EGFR and high NF-kappa B activity play a key role in the epithelial-to-mesenchymal transition, which is of critical importance in the processes underlying metastasis, and we found treatment with GSPs enhanced the levels of epithelial (E-cadherin, cytokeratins and desmoglein-2) and reduced the levels of mesenchymal (vimentin, fibronectin, N-cadherin and Slug) biomarkers in the OSC19 cells. These results indicate that GSPs have the ability to inhibit HNSCC cell invasion, and do so by targeting the expression of EGFR and activation of NF-kappa B as well as inhibiting the epithelial-to-mesenchymal transition. C1 [Sun, Qian; Prasad, Ram; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Rosenthal, Eben] Univ Alabama, Dept Surg Otolaryngol, Birmingham, AL USA. [Rosenthal, Eben; Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. RP Sun, Q (reprint author), Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU Veterans Administration FX This work was supported by funds from the Veterans Administration Merit Review Award (SKK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 13 Z9 17 U1 1 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 JAN 27 PY 2012 VL 7 IS 1 AR e31093 DI 10.1371/journal.pone.0031093 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 911GB UT WOS:000301704200059 PM 22299051 ER PT J AU Kogai, T Liu, YY Mody, K Shamsian, DV Brent, GA AF Kogai, Takahiko Liu, Yan-Yun Mody, Kaizeen Shamsian, Deborah V. Brent, Gregory A. TI Regulation of Sodium Iodide Symporter Gene Expression by Rac1/p38 beta Mitogen-activated Protein Kinase Signaling Pathway in MCF-7 Breast Cancer Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THYROID-STIMULATING HORMONE; TRANS-RETINOIC ACID; SODIUM/IODIDE SYMPORTER; SELECTIVE ACTIVATION; RADIOIODIDE UPTAKE; NIS; RADIOVIROTHERAPY; TRANSPORTER; INHIBITION; ISOFORMS AB Activation of p38 MAPK is a key pathway for cell proliferation and differentiation in breast cancer and thyroid cells. The sodium/iodide symporter (NIS) concentrates iodide in the thyroid and lactating breast. All-trans-retinoic acid (tRA) markedly induces NIS activity in some breast cancer cell lines and promotes uptake of beta-emitting radioiodide I-131 sufficient for targeted cytotoxicity. To identify a signal transduction pathway that selectively stimulates NIS expression, we investigated regulation by the Rac1-p38 signaling pathway in MCF-7 breast cancer cells and compared it with regulation in FRTL-5 rat thyroid cells. Loss of function experiments with pharmacologic inhibitors and small interfering RNA, as well as RT-PCR analysis of p38 isoforms, demonstrated the requirement of Rac1, MAPK kinase 3B, and p38 beta for the full expression of NIS in MCF-7 cells. In contrast, p38 alpha was critical for NIS expression in FRTL-5 cells. Treatment with tRA or overexpression of Rac1 induced the phosphorylation of p38 isoforms, including p38 beta. A dominant negative mutant of Rac1 abolished tRA-induced phosphorylation in MCF-7 cells. Overexpression of p38 beta or Rac1 significantly enhanced (1.9- and 3.9-fold, respectively), the tRA-stimulated NIS expression in MCF-7 cells. This study demonstrates differential regulation of NIS by distinct p38 isoforms in breast cancer cells and thyroid cells. Targeting isoform-selective activation of p38 may enhance NIS induction, resulting in higher efficacy of I-131 concentration and treatment of breast cancer. C1 [Kogai, Takahiko; Brent, Gregory A.] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. RP Kogai, T (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Bldg 114,Rm 229,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM tkogai@ucla.edu; gbrent@ucla.edu FU National Institutes of Health [RO1 CA089364]; Veterans Affairs Merit Review Funds FX This work was supported, in whole or in part, by National Institutes of Health Grant RO1 CA089364 (to G. A. B.). This work was also supported by Veterans Affairs Merit Review Funds. NR 37 TC 6 Z9 6 U1 0 U2 6 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 JAN 27 PY 2012 VL 287 IS 5 BP 3292 EP 3300 DI 10.1074/jbc.M111.315523 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 892OI UT WOS:000300295100035 PM 22157753 ER PT J AU Wei, R Bhattacharya, A Chintalaramulu, N Jernigan, AL Liu, YH Van Remmen, H Chaudhuri, AR AF Wei, Rochelle Bhattacharya, Arunabh Chintalaramulu, Naveen Jernigan, Amanda L. Liu, Yuhong Van Remmen, Holly Chaudhuri, Asish R. TI Protein misfolding, mitochondrial dysfunction and muscle loss are not directly dependent on soluble and aggregation state of mSOD1 protein in skeletal muscle of ALS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Protein misfolding; Mitochondria; Reactive oxygen species; G93A; ALS ID AMYOTROPHIC-LATERAL-SCLEROSIS; OXIDATIVE STRESS; SOD1; RESISTANCE; TARGET AB Mutant superoxide dismutase 1 (mSOD1) is often found as aggregates at the outer-membrane of mitochondria in motor neurons of various mouse models and familial amyotrophic lateral sclerosis (f-ALS) patients. It has been postulated that disruption of mitochondrial function by physical association of misfolded mSOD1 aggregates may actually be the trigger for initiation of degeneration of motor neurons in ALS. However, it was not clear if the same mechanism is involved in muscle degeneration and mitochondrial dysfunction in skeletal muscles of ALS. Recent study from our laboratory show that two skeletal muscle proteins, namely creatine kinase (CK) and glyceraldehydes-3-phosphate dehydrogenase (GAPDH) undergo major conformational and functional changes in the f-ALS mouse model of ALS (G93A). In this paper, we report two intriguing observations which are as follows:(i) G93A protein does not form aggregates in skeletal muscle at any stages of disease process probably due to high chymotrypsin-like activity of proteasome and thus G93A protein aggregates have no direct effects on progressive loss of muscle mass and global changes in protein conformation in ALS, and (ii) the soluble G93A protein does not have direct effects on mitochondrial dysfunction as determined by quantifying the release of reactive oxygen species (ROS) in skeletal muscle mitochondria; instead, the proteins affected by G93A possibly affect mitochondrial ROS release. These data strongly suggest for the first time that unlike in motor neurons, the soluble and aggregation states of the G93A protein do not have direct effects on protein misfolding and mitochondrial dysfunction in skeletal muscle during ALS. Published by Elsevier Inc. C1 [Chaudhuri, Asish R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Bhattacharya, Arunabh; Jernigan, Amanda L.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Wei, Rochelle; Bhattacharya, Arunabh; Chintalaramulu, Naveen; Liu, Yuhong; Van Remmen, Holly; Chaudhuri, Asish R.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Van Remmen, Holly; Chaudhuri, Asish R.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Chaudhuri, AR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Texas Res Pk Campus,15355 Lambda Dr, San Antonio, TX 78245 USA. EM chaudhuria@uthscsa.edu FU Veteran Affair Merit Grant Award FX This work was supported by the Veteran Affair Merit Grant Award (AC). NR 23 TC 12 Z9 12 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 27 PY 2012 VL 417 IS 4 BP 1275 EP 1279 DI 10.1016/j.bbrc.2011.12.126 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 891DG UT WOS:000300196100029 PM 22234310 ER PT J AU Zhang, T Inesta-Vaquera, F Niepel, M Zhang, JM Ficarro, SB Machleidt, T Xie, T Marto, JA Kim, N Sim, T Laughlin, JD Park, H LoGrasso, PV Patricelli, M Nomanbhoy, TK Sorger, PK Alessi, DR Gray, NS AF Zhang, Tinghu Inesta-Vaquera, Francisco Niepel, Mario Zhang, Jianming Ficarro, Scott B. Machleidt, Thomas Xie, Ting Marto, Jarrod A. Kim, NamDoo Sim, Taebo Laughlin, John D. Park, Hajeung LoGrasso, Philip V. Patricelli, Matt Nomanbhoy, Tyzoon K. Sorger, Peter K. Alessi, Dario R. Gray, Nathanael S. TI Discovery of Potent and Selective Covalent Inhibitors of JNK SO CHEMISTRY & BIOLOGY LA English DT Article ID N-TERMINAL-KINASE; INSULIN-RECEPTOR SUBSTRATE-1; ACTIVATED PROTEIN-KINASES; TYROSINE KINASE; SIGNAL-TRANSDUCTION; CYTOKINE PRODUCTION; IN-VIVO; MAP; PHOSPHORYLATION; PATHWAYS AB The mitogen-activated kinases JNK1/2/3 are key enzymes in signaling modules that transduce and integrate extracellular stimuli into coordinated cellular response. Here, we report the discovery of irreversible inhibitors of JNK1/2/3. We describe two JNK3 cocrystal structures at 2.60 and 2.97 angstrom resolution that show the compounds form covalent bonds with a conserved cysteine residue. JNK-IN-8 is a selective JNK inhibitor that inhibits phosphorylation of c-Jun, a direct substrate of JNK, in cells exposed to submicromolar drug in a manner that depends on covalent modification of the conserved cysteine residue. Extensive biochemical, cellular, and pathway-based profiling establish the selectivity of JNK-IN-8 for JNK and suggests that the compound will be broadly useful as a pharmacological probe of JNK-dependent signal transduction. Potential lead compounds have also been identified for kinases, including IRAK1, PIK3C3, PIP4K2C, and PIP5K3. C1 [Zhang, Tinghu; Zhang, Jianming; Ficarro, Scott B.; Xie, Ting; Marto, Jarrod A.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Zhang, Tinghu; Zhang, Jianming; Ficarro, Scott B.; Xie, Ting; Marto, Jarrod A.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Inesta-Vaquera, Francisco; Alessi, Dario R.] Univ Dundee, Coll Life Sci, Sir James Black Ctr, MRC Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland. [Niepel, Mario; Sorger, Peter K.] Harvard Univ, Sch Med, Dept Syst Biol, Ctr Cell Decis Proc, Boston, MA 02115 USA. [Ficarro, Scott B.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Machleidt, Thomas] Primary & Stem Cell Syst Life Technol, Madison, WI 53719 USA. [Kim, NamDoo; Sim, Taebo] Korea Inst Sci & Technol, Future Convergence Res Div, Seoul 136791, South Korea. [Laughlin, John D.; Park, Hajeung; LoGrasso, Philip V.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA. [Laughlin, John D.; Park, Hajeung; LoGrasso, Philip V.] Scripps Res Inst, Translat Res Inst, Jupiter, FL 33458 USA. [Patricelli, Matt; Nomanbhoy, Tyzoon K.] ActivX Biosci, La Jolla, CA 92037 USA. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA. EM nathanael_gray@dfci.harvard.edu RI Niepel, Mario/G-5443-2011; OI Niepel, Mario/0000-0003-1415-6295; Alessi, Dario/0000-0002-2140-9185 FU NIH [U54 HG006097, 1RC2HG005693, 5 RCD HG005693-02, 5 RC2 CA148164-02, 1 U54 HG 006907-01, NS057153-04]; American Skin Association; Milstein Innovation Award; Medical Research Council UK; Wellcome Trust FX Funding was provided by NIH U54 HG006097, NIH 1RC2HG005693, 5 RCD HG005693-02, 5 RC2 CA148164-02, 1 U54 HG 006907-01, NS057153-04, and American Skin Association, Milstein Innovation Award. Thanks to Kendall Nettles for help with the determination of JNK3 inhibitor structures. Thanks to the Medical Research Council UK, the Wellcome Trust, and the pharmaceutical companies supporting the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KgaA, and Pfizer). Special thanks to Lili Zhou for assistance with high-throughput microscopy and Eddy Goh and Philip Cohen for developing the cellular IRAK1 assays and helpful discussions. NR 63 TC 83 Z9 83 U1 1 U2 32 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JAN 27 PY 2012 VL 19 IS 1 SI SI BP 140 EP 154 DI 10.1016/j.chembiol.2011.11.010 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 889LF UT WOS:000300074500014 PM 22284361 ER PT J AU Haining, WN AF Haining, W. Nicholas TI The Numerology of T Cell Functional Diversity SO IMMUNITY LA English DT Editorial Material ID GENE-EXPRESSION; DIFFERENTIATION; HETEROGENEITY; MEMORY AB Memory T cells are heterogeneous in phenotype and function. In this issue of Immunity, Newell et al. (2012) use a new flow cytometry platform to show that the functional heterogeneity of the human T cell compartment is even greater than previously thought. C1 [Haining, W. Nicholas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Haining, W. Nicholas] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Haining, WN (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM nicholas_haining@dfci.harvard.edu FU NIAID NIH HHS [U19 AI082630-02, R01 AI091493-03, R01 AI091493, U19 AI082630] NR 10 TC 2 Z9 2 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN 27 PY 2012 VL 36 IS 1 BP 10 EP 12 DI 10.1016/j.immuni.2012.01.006 PG 3 WC Immunology SC Immunology GA 885GG UT WOS:000299766000005 PM 22284416 ER PT J AU Oku, M Okumi, M Shimizu, A Sahara, H Setoyama, K Nishimura, H Sada, M Scalea, J Ido, A Sachs, DH Tsubouchi, H Yamada, K AF Oku, Manei Okumi, Masayoshi Shimizu, Akira Sahara, Hisashi Setoyama, Kentaro Nishimura, Hiroaki Sada, Masaharu Scalea, Joseph Ido, Akio Sachs, David H. Tsubouchi, Hirohito Yamada, Kazuhiko TI Hepatocyte Growth Factor Sustains T Regulatory Cells and Prolongs the Survival of Kidney Allografts in Major Histocompatibility Complex-Inbred CLAWN-Miniature Swine SO TRANSPLANTATION LA English DT Article DE Human recombinant HGF; CLAWN-miniature swine; Kidney transplantation; Immunosuppression ID MISMATCHED RENAL-ALLOGRAFTS; SLA CLASS-I; TRANSPLANTATION TOLERANCE; STABLE INDUCTION; THYMUS; COTRANSPLANTATION; RECIPIENTS; CHIMERISM; MOTILITY; RATS AB Background. Although 12 days of high dose of FK506 permits the induction of tolerance of fully major histocompatibility complex (MHC)-mismatched allogeneic kidneys in MGH-miniature swine, we found that the same dose of FK506 is insufficient to induce such tolerance CLAWN-miniature swine. The CLAWN swine model was therefore chosen to study the potential immunoregulatory effects of human-recombinant hepatocyte growth factor (HGF). Methods. Ten CLAWN miniature swine received fully MHC-mismatched kidneys with 12 days (days 0-11) of FK506. Among these 10 recipients, 4 received 7 or 14 days of human-recombinant HGF starting at day 11. Graft function was assessed by daily serum creatinine and biopsies. Immunologic assays, including CD4/CD25 DP and FoxP3+ cells and development of antidonor antibodies, were performed. Results. Without HGF, all six CLAWN recipients developed severe acute rejection (Cre >9 mg/dL) within 3 weeks of transplantation. In contrast, in the four animals that received HGF for 7 to 14 days, stable renal function was observed for more than 50 days, although all grafts were ultimately rejected by postoperative day 80. Percent FoxP3+ cells in the CD4+CD25+ double positive population (T regulatory cells) in peripheral blood monocyte cells decreased in recipients with FK506 induction monotherapy while no reduction was observed in recipients treated with FK506 and HGF. Conclusion. This study demonstrates that in CLAWN swine treated with a dose of FK506 insufficient to induce tolerance across a fully MHC mismatched barrier, a short course of HGF may inhibit acute rejection while maintaining T regulatory cells. To our knowledge, this study provides the first evidence in a large animal transplantation model of HGF's immunoprotective effects. C1 [Yamada, Kazuhiko] Kagoshima Univ, Organ Replacement & Xenotransplant Surg Sect, Frontier Sci Res Ctr, Div Xenotransplantat Surg, Kagoshima 8908520, Japan. [Oku, Manei; Ido, Akio; Tsubouchi, Hirohito] Kagoshima Univ, Dept Digest & Life Style Related Dis, Grad Sch Med & Dent Sci, Kagoshima 8908520, Japan. [Shimizu, Akira; Scalea, Joseph; Sachs, David H.; Yamada, Kazuhiko] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Yamada, K (reprint author), Kagoshima Univ, Organ Replacement & Xenotransplant Surg Sect, Frontier Sci Res Ctr, Div Xenotransplantat Surg, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan. EM kaz.yamada@tbrc.mgh.harvard.edu FU Kagoshima University; [19390422]; [19209043] FX This work was supported by Grant-in-Aid for Scientific Research (B) 19390422 (M.S. and K.Y.), Grant-in-Aid for Scientific Research (A) 19209043 (K.Y) and the Kagoshima University Research Awards (K.Y.). NR 31 TC 6 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 2012 VL 93 IS 2 BP 148 EP 155 DI 10.1097/TP.0b013e31823be83f PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 877FZ UT WOS:000299164000009 PM 22158517 ER PT J AU Xu, J Hedberg, C Dekker, FJ Li, Q Haigis, KM Hwang, E Waldmann, H Shannon, K AF Xu, Jin Hedberg, Christian Dekker, Frank J. Li, Qing Haigis, Kevin M. Hwang, Eugene Waldmann, Herbert Shannon, Kevin TI Inhibiting the palmitoylation/depalmitoylation cycle selectively reduces the growth of hematopoietic cells expressing oncogenic Nras SO BLOOD LA English DT Article ID CHRONIC MYELOMONOCYTIC LEUKEMIA; HYPERACTIVE RAS; MUTATIONS; LOCALIZATION; LEUKEMOGENESIS; PALMITOYLATION; ISOFORMS; CANCER; KRAS AB The palmitoylation/depalmitoylation cycle of posttranslational processing is a potential therapeutic target for selectively inhibiting the growth of hematologic cancers with somatic NRAS mutations. To investigate this question at the single-cell level, we constructed murine stem cell virus vectors and assayed the growth of myeloid progenitors. Whereas cells expressing oncogenic N-Ras(G12D) formed cytokine-independent colonies and were hypersensitive to GMCSF, mutations within the N-Ras hypervariable region induced N-Ras mislocalization and attenuated aberrant progenitor growth. Exposing transduced hematopoietic cells and bone marrow from Nras and Kras mutant mice to the acyl protein thioesterase inhibitor palmostatin B had similar effects on protein localization and colony growth. Importantly, palmostatin B-mediated inhibition was selective for Nras mutant cells, and we mapped this activity to the hypervariable region. These data support the clinical development of depalmitoylation inhibitors as a novel class of rational therapeutics in hematologic malignancies with NRAS mutations. (Blood. 2012;119(4):1032-1035) C1 [Xu, Jin; Hwang, Eugene; Shannon, Kevin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA. [Hedberg, Christian; Waldmann, Herbert] Max Planck Inst Mol Physiol, Dept Chem Biol, D-44139 Dortmund, Germany. [Dekker, Frank J.] Univ Groningen, Univ Ctr Pharm, Groningen, Netherlands. [Li, Qing] Univ Michigan, Dept Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Shannon, Kevin] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA. RP Shannon, K (reprint author), Univ Calif San Francisco, Dept Pediat, Helen Diller Family Canc Res Bldg,1450 3rd St,Rm, San Francisco, CA 94158 USA. EM shannonk@peds.ucsf.edu RI Dekker, Frank/H-2544-2014; OI Dekker, Frank/0000-0001-7217-9300; Waldmann, Herbert/0000-0002-9606-7247 FU National Institutes of Health [R37 CA72614, K08 CA 134649]; Leukemia & Lymphoma Society; Frank A. Campini Foundation; American Cancer Research Society FX This work was supported by the National Institutes of Health (grant R37 CA72614, and an American Recovery and Reinvestment Act supplement to this award; grant K08 CA 134649), the Leukemia & Lymphoma Society (Specialized Center of Research award), the Frank A. Campini Foundation, and the American Cancer Research Society (Post-Doctoral Fellowship award, J.X.). K.S. is an American Cancer Society Research Professor. NR 22 TC 26 Z9 26 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 26 PY 2012 VL 119 IS 4 BP 1032 EP 1035 DI 10.1182/blood-2011-06-358960 PG 4 WC Hematology SC Hematology GA 886NI UT WOS:000299860700018 PM 22144181 ER PT J AU Borsook, D Maleki, N Becerra, L McEwen, B AF Borsook, David Maleki, Nasim Becerra, Lino McEwen, Bruce TI Understanding Migraine through the Lens of Maladaptive Stress Responses: A Model Disease of Allostatic Load SO NEURON LA English DT Review ID TENSION-TYPE HEADACHE; PREMENSTRUAL DYSPHORIC DISORDER; MAGNETIC-RESONANCE-SPECTROSCOPY; CORTICAL SPREADING DEPRESSION; FAMILIAL HEMIPLEGIC MIGRAINE; MEDICATION-OVERUSE; NERVOUS-SYSTEM; CENTRAL SENSITIZATION; PREMONITORY SYMPTOMS; MATTER ABNORMALITIES AB The brain and body respond to potential and actual stressful events by activating hormonal and neural mediators and modifying behaviors to adapt. Such responses help maintain physiological stability ("allostasis"). When behavioral or physiological stressors are frequent and/or severe, allostatic responses can become dysregulated and maladaptive ("allostatic load"). Allostatic load may alter brain networks both functionally and structurally. As a result, the brain's responses to continued/subsequent stressors are abnormal, and behavior and systemic physiology are altered in ways that can, in a vicious cycle, lead to further allostatic load. Migraine patients are continually exposed to such stressors, resulting in changes to central and peripheral physiology and function. Here we review how changes in brain states that occur as a result of repeated migraines may be explained by a maladaptive feedforward allostatic cascade model and how understanding migraine within the context of allostatic load model suggests alternative treatments for this often-debilitating disease. C1 [Borsook, David; Maleki, Nasim; Becerra, Lino] Harvard Univ, Sch Med, Ctr Pain & Brain, McLean Hosp, Boston, MA 02115 USA. [Borsook, David; Maleki, Nasim; Becerra, Lino] Harvard Univ, Sch Med, Ctr Pain & Brain, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Borsook, David; Maleki, Nasim; Becerra, Lino] Harvard Univ, Sch Med, Ctr Pain & Brain, Childrens Hosp, Boston, MA 02115 USA. [McEwen, Bruce] Rockefeller Univ, Lab Neuroendocrinol, New York, NY 10065 USA. RP Borsook, D (reprint author), Harvard Univ, Sch Med, Ctr Pain & Brain, McLean Hosp, Boston, MA 02115 USA. EM dborsook@partners.org FU National Institutes of Health, NINDS [K24 NS064050, R01 NS073997]; Louis Herlands Fund for Pain Research FX The work was supported in part by a grant from the National Institutes of Health (K24 NS064050 and R01 NS073997, NINDS) to D.B. and the Louis Herlands Fund for Pain Research (D.B., L.B.). NR 195 TC 77 Z9 82 U1 2 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD JAN 26 PY 2012 VL 73 IS 2 BP 219 EP 234 DI 10.1016/j.neuron.2012.01.001 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 885EP UT WOS:000299761600005 PM 22284178 ER PT J AU Bostrom, P Wu, J Jedrychowski, MP Korde, A Ye, L Lo, JC Rasbach, KA Bostrom, EA Choi, JH Long, JZ Kajimura, S Zingaretti, MC Vind, BF Tu, H Cinti, S Hojlund, K Gygi, SP Spiegelman, BM AF Bostroem, Pontus Wu, Jun Jedrychowski, Mark P. Korde, Anisha Ye, Li Lo, James C. Rasbach, Kyle A. Bostroem, Elisabeth Almer Choi, Jang Hyun Long, Jonathan Z. Kajimura, Shingo Zingaretti, Maria Cristina Vind, Birgitte F. Tu, Hua Cinti, Saverio Hojlund, Kurt Gygi, Steven P. Spiegelman, Bruce M. TI A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis SO NATURE LA English DT Article ID SKELETAL-MUSCLE; ADIPOSE-TISSUE; EXERCISE; PGC-1-ALPHA; PROTECTS; PHOSPHORYLATION; COACTIVATOR; EXPRESSION; MYOBLAST; DISEASE AB Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-gamma co-activator-1 alpha (PGC1-alpha). Here we show in mouse that PGC1-alpha expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise. C1 [Bostroem, Pontus; Wu, Jun; Korde, Anisha; Ye, Li; Lo, James C.; Rasbach, Kyle A.; Choi, Jang Hyun; Long, Jonathan Z.; Spiegelman, Bruce M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jedrychowski, Mark P.; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Bostroem, Elisabeth Almer] Harvard Univ, Sch Med, Div Renal, Brigham & Womens Hosp, Boston, MA 02115 USA. [Kajimura, Shingo] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Kajimura, Shingo] Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA. [Zingaretti, Maria Cristina; Cinti, Saverio] Univ Politecn Marche, Dept Expt & Clin Med, Azienda Osped Riuniti, Electron Microscopy Unit, I-60020 Ancona, Italy. [Vind, Birgitte F.; Hojlund, Kurt] Odense Univ Hosp, Diabet Res Ctr, Dept Endocrinol, DK-5000 Odense, Denmark. [Tu, Hua] LakePharma Inc, Belmont, CA 94002 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, 3 Blackfan Circle,CLS Bldg,Floor 11, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu RI Choi, Jang Hyun/B-3055-2012 FU National Institutes of Health [DK54477, DK31405, DK61562]; Wenner-Gren Foundation; Swedish Heart and Lung Foundation; Svenska Sallskapet for Medicinsk Forskning; American Heart Association [09POST2010078] FX This study was supported by National Institutes of Health grants DK54477, DK31405, DK61562 to B. M. S. P. B. and E. A. B. were supported by the Wenner-Gren Foundation, Swedish Heart and Lung Foundation and the 'Svenska Sallskapet for Medicinsk Forskning'. J.W. was supported by a postdoctoral fellowship from the American Heart Association (Founders Affiliate #09POST2010078). The animal procedures were in accordance with Institutional Animal Use and Care Committee protocols 110-2008 and 056-2009. The authors thank S. Loffredo and M. Kirschner for discussions and suggestions on the manuscript. NR 26 TC 983 Z9 1063 U1 31 U2 240 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 26 PY 2012 VL 481 IS 7382 BP 463 EP U72 DI 10.1038/nature10777 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 881GY UT WOS:000299471800031 PM 22237023 ER PT J AU He, CC Bassik, MC Moresi, V Sun, K Wei, YJ Zou, ZJ An, ZY Loh, J Fisher, J Sun, QH Korsmeyer, S Packer, M May, HI Hill, JA Virgin, HW Gilpin, C Xiao, GH Bassel-Duby, R Scherer, PE Levine, B AF He, Congcong Bassik, Michael C. Moresi, Viviana Sun, Kai Wei, Yongjie Zou, Zhongju An, Zhenyi Loh, Joy Fisher, Jill Sun, Qihua Korsmeyer, Stanley Packer, Milton May, Herman I. Hill, Joseph A. Virgin, Herbert W. Gilpin, Christopher Xiao, Guanghua Bassel-Duby, Rhonda Scherer, Philipp E. Levine, Beth TI Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis SO NATURE LA English DT Article ID CAUSES INSULIN-RESISTANCE; MICE; BECLIN-1; MOUSE; GENE; DIET; PHOSPHORYLATION; TUMORIGENESIS; SENSITIVITY; DISRUPTION AB Exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes(1). However, the cellular mechanisms underlying these effects are incompletely understood. The lysosomal degradation pathway, autophagy, is an intracellular recycling system that functions during basal conditions in organelle and protein quality control(2). During stress, increased levels of autophagy permit cells to adapt to changing nutritional and energy demands through protein catabolism(3). Moreover, in animal models, autophagy protects against diseases such as cancer, neurodegenerative disorders, infections, inflammatory diseases, ageing and insulin resistance(4-6). Here we show that acute exercise induces autophagy in skeletal and cardiac muscle of fed mice. To investigate the role of exercise-mediated autophagy in vivo, we generated mutant mice that show normal levels of basal autophagy but are deficient in stimulus (exercise- or starvation)-induced autophagy. These mice (termed BCL2 AAA mice) contain knock-in mutations in BCL2 phosphorylation sites (Thr69Ala, Ser70Ala and Ser84Ala) that prevent stimulus-induced disruption of the BCL2-beclin-1 complex and autophagy activation. BCL2 AAA mice show decreased endurance and altered glucose metabolism during acute exercise, as well as impaired chronic exercise-mediated protection against high-fat-diet-induced glucose intolerance. Thus, exercise induces autophagy, BCL2 is a crucial regulator of exercise- (and starvation)-induced autophagy in vivo, and autophagy induction may contribute to the beneficial metabolic effects of exercise. C1 [He, Congcong; Wei, Yongjie; Zou, Zhongju; An, Zhenyi; Sun, Qihua; Levine, Beth] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA. [He, Congcong; Sun, Kai; Wei, Yongjie; Zou, Zhongju; An, Zhenyi; Sun, Qihua; May, Herman I.; Hill, Joseph A.; Scherer, Philipp E.; Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [He, Congcong; Wei, Yongjie; Zou, Zhongju; Levine, Beth] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [Bassik, Michael C.; Fisher, Jill; Korsmeyer, Stanley] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moresi, Viviana; Bassel-Duby, Rhonda] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. [Sun, Kai; Scherer, Philipp E.] Univ Texas SW Med Ctr Dallas, Touchstone Diabet Ctr, Dallas, TX 75390 USA. [Loh, Joy; Virgin, Herbert W.] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO USA. [Packer, Milton; Xiao, Guanghua] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Gilpin, Christopher] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. RP Levine, B (reprint author), Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM beth.levine@utsouthwestern.edu RI Moresi, Viviana /N-7977-2013; An, Zhenyi/H-9061-2016 FU National Institutes of Health [RO1 CA109618, ROI HL080244, ROI HL090842, ROI AI084887, RCI DK086629, RO1 CA112023, 1PO1 DK0887761] FX We thank the UT Southwestern Mouse Metabolic Phenotyping Core and E. Berglund for assistance with metabolic measurements, J. Shelton for assistance with muscle stains, N. Mizushima for critical reagents, and B. D. Levine for expert advice. This work was supported by National Institutes of Health grants RO1 CA109618 (B. L.), ROI HL080244 (J. A. H.), ROI HL090842 (J. A. H.), ROI AI084887 (H. W. V.), RCI DK086629 (P. E. S.), RO1 CA112023 (P. E. S.) and 1PO1 DK0887761 (P.E.S.). NR 32 TC 354 Z9 375 U1 11 U2 118 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 26 PY 2012 VL 481 IS 7382 BP 511 EP U126 DI 10.1038/nature10758 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 881GY UT WOS:000299471800041 PM 22258505 ER PT J AU Melendez, E Goldstein, AM Sagar, P Badizadegan, K AF Melendez, Elliot Goldstein, Allan M. Sagar, Pallavi Badizadegan, Kamran TI A Newborn Boy with Vomiting, Diarrhea, and Abdominal Distention Hirschsprung's disease with enterocolitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID POSTOPERATIVE ENTEROCOLITIS; CALRETININ IMMUNOHISTOCHEMISTRY; SEPTIC SHOCK; RISK-FACTORS; 1ST STOOL; DIAGNOSIS; INFANTS; AGE; BIOPSIES; CHILDREN C1 [Melendez, Elliot] Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. [Melendez, Elliot] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Goldstein, Allan M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sagar, Pallavi] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Badizadegan, Kamran] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Melendez, Elliot] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Goldstein, Allan M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Sagar, Pallavi] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Badizadegan, Kamran] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Melendez, E (reprint author), Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. NR 26 TC 4 Z9 5 U1 0 U2 3 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 JAN 26 PY 2012 VL 366 IS 4 BP 361 EP 372 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 881EQ UT WOS:000299464100009 PM 22276826 ER PT J AU Christie, JD Wurfel, MM Feng, R O'Keefe, GE Bradfield, J Ware, LB Christiani, DC Calfee, CS Cohen, MJ Matthay, M Meyer, NJ Kim, C Li, MY Akey, J Barnes, KC Sevransky, J Lanken, PN May, AK Aplenc, R Maloney, JP Hakonarson, H AF Christie, Jason D. Wurfel, Mark M. Feng, Rui O'Keefe, Grant E. Bradfield, Jonathan Ware, Lorraine B. Christiani, David C. Calfee, Carolyn S. Cohen, Mitchell J. Matthay, Michael Meyer, Nuala J. Kim, Cecilia Li, Mingyao Akey, Joshua Barnes, Kathleen C. Sevransky, Jonathan Lanken, Paul N. May, Addison K. Aplenc, Richard Maloney, James P. Hakonarson, Hakon CA Trauma ALI SNP Consortium TASC TI Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma SO PLOS ONE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; MANNOSE-BINDING LECTIN; CHAIN-KINASE GENE; HUMAN-DISEASE; EARLY RELEASE; T-CELLS; POLYMORPHISM; ARDS; MORTALITY; PROTEIN AB Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated Blymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multicenter GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research. C1 [Christie, Jason D.; Meyer, Nuala J.; Lanken, Paul N.] Univ Penn, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA. [Christie, Jason D.; Feng, Rui; Li, Mingyao] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [O'Keefe, Grant E.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA. [Wurfel, Mark M.] Univ Washington, Harborview Med Ctr, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. [Bradfield, Jonathan; Kim, Cecilia; Hakonarson, Hakon] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Human Genet,Ctr Appl Genom, Philadelphia, PA 19104 USA. [Ware, Lorraine B.] Vanderbilt Univ, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN USA. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Calfee, Carolyn S.; Matthay, Michael] Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA. [Calfee, Carolyn S.; Matthay, Michael] Univ Calif San Francisco, Cardiovasc Res Inst, Dept Anesthesia, San Francisco, CA 94143 USA. [Cohen, Mitchell J.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Akey, Joshua] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Barnes, Kathleen C.; Sevransky, Jonathan] Johns Hopkins Univ, Sch Med, Div Pulm Allergy & Crit Care Med, Baltimore, MD USA. [May, Addison K.] Vanderbilt Univ, Dept Surg Sci, Nashville, TN USA. [Aplenc, Richard] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Oncol, Philadelphia, PA 19104 USA. [Maloney, James P.] Univ Colorado, Hlth Sci Ctr, Div Pulm & Crit Care Med, Denver, CO USA. RP Christie, JD (reprint author), Univ Penn, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA. EM jchristi@mail.med.upenn.edu RI maloney, james/K-9428-2015 OI maloney, james/0000-0001-8348-4650 FU NIH [P50HL60290, P01HL079063, HL081332, HL060710] FX This study was funded by the following NIH grants: P50HL60290, P01HL079063, HL081332, HL060710. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 85 TC 21 Z9 23 U1 0 U2 1 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 JAN 25 PY 2012 VL 7 IS 1 AR e28268 DI 10.1371/journal.pone.0028268 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 910ME UT WOS:000301640600001 PM 22295056 ER PT J AU Pearson, ML Selby, JV Katz, KA Cantrell, V Braden, CR Parise, ME Paddock, CD Lewin-Smith, MR Kalasinsky, VF Goldstein, FC Hightower, AW Papier, A Lewis, B Motipara, S Eberhard, ML AF Pearson, Michele L. Selby, Joseph V. Katz, Kenneth A. Cantrell, Virginia Braden, Christopher R. Parise, Monica E. Paddock, Christopher D. Lewin-Smith, Michael R. Kalasinsky, Victor F. Goldstein, Felicia C. Hightower, Allen W. Papier, Arthur Lewis, Brian Motipara, Sarita Eberhard, Mark L. CA Unexplained Dermopathy Study Team TI Clinical, Epidemiologic, Histopathologic and Molecular Features of an Unexplained Dermopathy SO PLOS ONE LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE; BRACHIORADIAL PRURITUS; MEDICAL OUTCOMES; PARASITOSIS; DELUSIONS; DIAGNOSIS; CULTURE; TISSUE; PCR AB Background: Morgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies. Methods: A descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006-2008. A case was defined as the self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations. We collected detailed epidemiologic data, performed clinical evaluations and geospatial analyses and analyzed materials collected from participants' skin. Results: We identified 115 case-patients. The prevalence was 3.65 (95% CI = 2.98, 4.40) cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113). Case-patients had a median age of 52 years (range: 17-93) and were primarily female (77%) and Caucasian (77%). Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9) and 35.45 (SD = 12.89), respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies); skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin. Conclusions: This unexplained dermopathy was rare among this population of Northern California residents, but associated with significantly reduced health-related quality of life. No common underlying medical condition or infectious source was identified, similar to more commonly recognized conditions such as delusional infestation. C1 [Pearson, Michele L.] Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. [Selby, Joseph V.; Cantrell, Virginia; Motipara, Sarita] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Katz, Kenneth A.] Hlth & Human Serv Agcy, HIV STD & Hepatitis Branch, San Diego, CA USA. [Braden, Christopher R.] Ctr Dis Control & Prevent, Div Food Waterborne & Environm Dis, Atlanta, GA USA. [Parise, Monica E.; Hightower, Allen W.; Eberhard, Mark L.] Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Atlanta, GA USA. [Paddock, Christopher D.] Ctr Dis Control & Prevent, Div High Consequence Pathogens & Pathol, Atlanta, GA USA. [Lewin-Smith, Michael R.] Joint Pathol Ctr, Silver Spring, MD USA. [Kalasinsky, Victor F.] US Dept Vet Affairs, Off Res & Dev, Washington, DC USA. [Goldstein, Felicia C.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Papier, Arthur] Univ Rochester, Sch Med, Dept Dermatol, Rochester, NY USA. [Lewis, Brian] Agcy Tox Subst & Dis Registry, Div Hlth Studies, Atlanta, GA USA. RP Pearson, ML (reprint author), Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. EM mle1@cdc.gov FU Centers for Disease Control (CDC) and Prevention FX Funding for this study was provided by the Centers for Disease Control (CDC) and Prevention. Epidemiologists from the CDC participated in the study design, data collection and analysis, decision to publish, and preparation of the manuscript. NR 31 TC 27 Z9 27 U1 0 U2 10 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 JAN 25 PY 2012 VL 7 IS 1 AR e29908 DI 10.1371/journal.pone.0029908 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 910ME UT WOS:000301640600015 PM 22295070 ER PT J AU Ke, YG Voigt, NV Gothelf, KV Shih, WM AF Ke, Yonggang Voigt, Niels V. Gothelf, Kurt V. Shih, William M. TI Multilayer DNA Origami Packed on Hexagonal and Hybrid Lattices SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NANOSCALE SHAPES; FOLDING DNA; DEVICE AB "Scaffolded DNA origami" has been proven to be a powerful and efficient approach to construct two-dimensional or three-dimensional objects with great complexity. Multilayer DNA origami has been demonstrated with helices packing along either honeycomb-lattice geometry or square-lattice geometry. Here we report successful folding of multilayer DNA origami with helices arranged on a close-packed hexagonal lattice. This arrangement yields a higher density of helical packing and therefore higher resolution of spatial addressing than has been shown previously. We also demonstrate hybrid multilayer DNA origami with honeycomb-lattice, square-lattice, and hexagonal-lattice packing of helices all in one design. The availability of hexagonal close-packing of helices extends our ability to build complex structures using DNA nanotechnology. C1 [Ke, Yonggang; Shih, William M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ke, Yonggang; Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Shih, William M.] Harvard, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. [Voigt, Niels V.; Gothelf, Kurt V.] Aarhus Univ, Danish Natl Res Fdn, Interdisciplinary Nanosci Ctr iNANO, Ctr DNA Nanotechnol, DK-8000 Aarhus, Denmark. [Voigt, Niels V.; Gothelf, Kurt V.] Aarhus Univ, Dept Chem, DK-8000 Aarhus, Denmark. RP Shih, WM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM William_Shih@dfci.harvard.edu FU Wyss Institute for Biologically Inspired Engineering, ONR [N000014091118]; NIH New Innovator [1DP20DO04641-01]; Danish National Research Foundation FX This work was supported by Wyss Institute for Biologically Inspired Engineering, ONR (N000014091118), and NIH New Innovator (1DP20DO04641-01) grants to W.M.S. and by the Danish National Research Foundation support to K.V.G. NR 27 TC 35 Z9 36 U1 5 U2 53 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 25 PY 2012 VL 134 IS 3 BP 1770 EP 1774 DI 10.1021/ja209719k PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 903AD UT WOS:000301084400063 PM 22187940 ER PT J AU Kangovi, S Grande, D AF Kangovi, Shreya Grande, David TI Hospital Readmissions and Measures of Quality Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Kangovi, Shreya] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Grande, David] Univ Penn, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Kangovi, S (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. EM kangovi@mail.med.upenn.edu NR 4 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 JAN 25 PY 2012 VL 307 IS 4 BP 361 EP 362 DI 10.1001/jama.2012.12 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 881EP UT WOS:000299464000014 ER PT J AU Emanuel, EJ Pearson, SD AF Emanuel, Ezekiel J. Pearson, Steven D. TI Physician Autonomy and Health Care Reform SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Emanuel, Ezekiel J.] Univ Penn, Dept Med Eth & Hlth Policy, Perelman Sch Med, Philadelphia, PA 19104 USA. [Pearson, Steven D.] Massachusetts Gen Hosp, Inst Technol Assessment, Inst Clin & Econ Review, Boston, MA 02114 USA. RP Emanuel, EJ (reprint author), Univ Penn, Dept Med Eth & Hlth Policy, Perelman Sch Med, 122 Coll Hall, Philadelphia, PA 19104 USA. EM zemanuel@upenn.edu NR 9 TC 17 Z9 17 U1 0 U2 4 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 JAN 25 PY 2012 VL 307 IS 4 BP 367 EP 368 DI 10.1001/jama.2012.19 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 881EP UT WOS:000299464000020 PM 22274681 ER PT J AU Calvo, SE Compton, AG Hershman, SG Lim, SC Lieber, DS Tucker, EJ Laskowski, A Garone, C Liu, ST Jaffe, DB Christodoulou, J Fletcher, JM Bruno, DL Goldblatt, J DiMauro, S Thorburn, DR Mootha, VK AF Calvo, Sarah E. Compton, Alison G. Hershman, Steven G. Lim, Sze Chern Lieber, Daniel S. Tucker, Elena J. Laskowski, Adrienne Garone, Caterina Liu, Shangtao Jaffe, David B. Christodoulou, John Fletcher, Janice M. Bruno, Damien L. Goldblatt, Jack DiMauro, Salvatore Thorburn, David R. Mootha, Vamsi K. TI Molecular Diagnosis of Infantile Mitochondrial Disease with Targeted Next-Generation Sequencing SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; DNA-POLYMERASE-GAMMA; RESPIRATORY-CHAIN DISORDERS; COMPLEX I DEFICIENCY; GENETIC-VARIATION; ENCODED SUBUNIT; HIGH-THROUGHPUT; GENOME BROWSER; MUTATIONS; DATABASE AB Advances in next-generation sequencing (NGS) promise to facilitate diagnosis of inherited disorders. Although in research settings NGS has pinpointed causal alleles using segregation in large families, the key challenge for clinical diagnosis is application to single individuals. To explore its diagnostic use, we performed targeted NGS in 42 unrelated infants with clinical and biochemical evidence of mitochondrial oxidative phosphorylation disease. These devastating mitochondrial disorders are characterized by phenotypic and genetic heterogeneity, with more than 100 causal genes identified to date. We performed "MitoExome" sequencing of the mitochondrial DNA (mtDNA) and exons of similar to 1000 nuclear genes encoding mitochondrial proteins and prioritized rare mutations predicted to disrupt function. Because patients and healthy control individuals harbored a comparable number of such heterozygous alleles, we could not prioritize dominant-acting genes. However, patients showed a fivefold enrichment of genes with two such mutations that could underlie recessive disease. In total, 23 of 42 (55%) patients harbored such recessive genes or pathogenic mtDNA variants. Firm diagnoses were enabled in 10 patients (24%) who had mutations in genes previously linked to disease. Thirteen patients (31%) had mutations in nuclear genes not previously linked to disease. The pathogenicity of two such genes, NDUFB3 and AGK, was supported by complementation studies and evidence from multiple patients, respectively. The results underscore the potential and challenges of deploying NGS in clinical settings. C1 [Compton, Alison G.; Lim, Sze Chern; Tucker, Elena J.; Laskowski, Adrienne; Bruno, Damien L.; Thorburn, David R.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [Calvo, Sarah E.; Hershman, Steven G.; Lieber, Daniel S.; Liu, Shangtao; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Calvo, Sarah E.; Hershman, Steven G.; Lieber, Daniel S.; Liu, Shangtao; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Calvo, Sarah E.; Hershman, Steven G.; Lieber, Daniel S.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Calvo, Sarah E.; Hershman, Steven G.; Lieber, Daniel S.; Jaffe, David B.; Mootha, Vamsi K.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02141 USA. [Lim, Sze Chern; Tucker, Elena J.; Thorburn, David R.] Univ Melbourne, Dept Paediat, Melbourne, Vic 3052, Australia. [Garone, Caterina; DiMauro, Salvatore] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Garone, Caterina] Univ Turin, Human Genet Joint PhD Programme, I-10125 Turin, Italy. [Garone, Caterina] Univ Bologna, I-40125 Bologna, Italy. [Christodoulou, John] Childrens Hosp Westmead, Genet Metab Disorders Res Unit, Westmead, NSW 2145, Australia. [Christodoulou, John] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia. [Christodoulou, John] Univ Sydney, Discipline Genet Med, Sydney, NSW 2006, Australia. [Fletcher, Janice M.] Dept Genet & Mol Pathol, Adelaide, SA 5006, Australia. [Fletcher, Janice M.] Univ Adelaide, Discipline Paediat & Reprod Hlth, Adelaide, SA 5005, Australia. [Bruno, Damien L.; Thorburn, David R.] Royal Childrens Hosp, Victorian Clin Genet Serv, Melbourne, Vic 3052, Australia. [Goldblatt, Jack] Univ Western Australia, King Edward Mem Hosp, Genet Serv Western Australia, Perth, WA 6009, Australia. RP Thorburn, DR (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Flemington Rd, Parkville, Vic 3052, Australia. EM david.thorburn@mcri.edu.au; vamsi@hms.harvard.edu RI Tucker, Elena/B-3487-2012; Thorburn, David/G-6266-2013; Bruno, Damien/C-3665-2013; Christodoulou, John/E-5866-2015; Lim, Sze Chern/I-6763-2013; OI Lim, Sze Chern/0000-0003-0312-9937; Hershman, Steven/0000-0001-9167-7380; Garone, Caterina/0000-0003-4928-1037; thorburn, david/0000-0002-7725-9470; Compton, Alison/0000-0002-2725-7055; Christodoulou, John/0000-0002-8431-0641 FU NIH [R01GM077465, 1R01GM097136, HD32062]; Australian National Health and Medical Research Council [436901, 436906]; National Defense Science and Engineering Graduate fellowship; Melbourne Research Scholarship; Australian Postgraduate Award; Marriott Mitochondrial Disorders Clinical Research Fund; Victorian Government FX Funding: Supported by grants from the NIH (R01GM077465 and 1R01GM097136 to V. K. M.; HD32062 to S. D.), a grant and Principal Research Fellowship from the Australian National Health and Medical Research Council (436901 and 436906 to D. R. T.), a National Defense Science and Engineering Graduate fellowship (S. G. H.), a Melbourne Research Scholarship (S. C. L.), an Australian Postgraduate Award (E.J.T.), the Marriott Mitochondrial Disorders Clinical Research Fund (S. D.), and the Victorian Government's Operational Infrastructure Support Program (D.R.T.). NR 70 TC 162 Z9 170 U1 4 U2 38 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 JAN 25 PY 2012 VL 4 IS 118 AR 118ra10 DI 10.1126/scitranslmed.3003310 PG 15 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 882CR UT WOS:000299539500004 PM 22277967 ER PT J AU Mar, L Yang, FC Ma, QF AF Mar, Lynn Yang, Fu-Chia Ma, Qiufu TI Genetic marking and characterization of Tac2-expressing neurons in the central and peripheral nervous system SO MOLECULAR BRAIN LA English DT Article ID DORSAL-ROOT GANGLIA; SUBSTANCE-P; NOCICEPTIVE NEURONS; NITRIC-OXIDE; PKC-GAMMA; PAIN; MICE; RECEPTORS; ITCH; HORN AB Background: The neurocircuits that process somatic sensory information in the dorsal horn of the spinal cord are still poorly understood, with one reason being the lack of Cre lines for genetically marking or manipulating selective subpopulations of dorsal horn neurons. Here we describe Tac2-Cre mice that were generated to express the Cre recombinase gene from the Tac2 locus. Tachykinin 2 (Tac2) encodes a neurotransmitter, neurokinin B (NKB). Results: By crossing Tac2-Cre mice with ROSA26-tdTomato reporter mice, we directly visualized Tac2 lineage neurons in the dorsal root ganglia, the dorsal horn of the spinal cord, and many parts of the brain including the olfactory bulb, cerebral cortex, amygdala, hippocampus, habenula, hypothalamus, and cerebellum. This Tac2-Cre allele itself was a null allele for the Tac2 gene. Behavioral analyses showed that Tac2 homozygous null mice responded normally to a series of algogenic (pain-inducing) and pruritic (itch-inducing) stimuli. Conclusions: Tac2-Cre mice are a useful tool to mark specific subsets of neurons in the sensory ganglia, the dorsal spinal cord, and the brain. These mice can also be used for future genetic manipulations to study the functions of Tac2-expressing neurons or the functions of genes expressed in these neurons. C1 [Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02215 USA. RP Ma, QF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM qiufu_ma@dfci.harvard.edu FU NINDS NIH HHS [R01 NS047710] NR 40 TC 12 Z9 12 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-6606 J9 MOL BRAIN JI Mol. Brain PD JAN 24 PY 2012 VL 5 AR 3 DI 10.1186/1756-6606-5-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 008CC UT WOS:000308933800001 PM 22272772 ER PT J AU Poche, RA Sharma, R Garcia, MD Wada, AM Nolte, MJ Udan, RS Paik, JH DePinho, RA Bartlett, JD Dickinson, ME AF Poche, Ross A. Sharma, Ramaswamy Garcia, Monica D. Wada, Aya M. Nolte, Mark J. Udan, Ryan S. Paik, Ji-Hye DePinho, Ronald A. Bartlett, John D. Dickinson, Mary E. TI Transcription Factor FoxO1 Is Essential for Enamel Biomineralization SO PLOS ONE LA English DT Article ID LINKED AMELOGENESIS IMPERFECTA; TGF-BETA; OCULODENTODIGITAL DYSPLASIA; OSTEOBLAST DIFFERENTIATION; TOOTH MORPHOGENESIS; BREAST-CANCER; MICE DISPLAY; MOUSE MODEL; EXPRESSION; MUTATION AB The Transforming growth factor beta (Tgf-beta) pathway, by signaling via the activation of Smad transcription factors, induces the expression of many diverse downstream target genes thereby regulating a vast array of cellular events essential for proper development and homeostasis. In order for a specific cell type to properly interpret the Tgf-beta signal and elicit a specific cellular response, cell-specific transcriptional co-factors often cooperate with the Smads to activate a discrete set of genes in the appropriate temporal and spatial manner. Here, via a conditional knockout approach, we show that mice mutant for Forkhead Box O transcription factor FoxO1 exhibit an enamel hypomaturation defect which phenocopies that of the Smad3 mutant mice. Furthermore, we determined that both the FoxO1 and Smad3 mutant teeth exhibit changes in the expression of similar cohort of genes encoding enamel matrix proteins required for proper enamel development. These data raise the possibility that FoxO1 and Smad3 act in concert to regulate a common repertoire of genes necessary for complete enamel maturation. This study is the first to define an essential role for the FoxO family of transcription factors in tooth development and provides a new molecular entry point which will allow researchers to delineate novel genetic pathways regulating the process of biomineralization which may also have significance for studies of human tooth diseases such as amelogenesis imperfecta. C1 [Poche, Ross A.; Garcia, Monica D.; Wada, Aya M.; Udan, Ryan S.; Dickinson, Mary E.] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. [Dickinson, Mary E.] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA. [Sharma, Ramaswamy; Bartlett, John D.] Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Cambridge, MA 02138 USA. [Sharma, Ramaswamy; Bartlett, John D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Cambridge, MA 02138 USA. [Nolte, Mark J.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. [Paik, Ji-Hye] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. [DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA. [DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Med, Boston, MA 02115 USA. [DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Genet, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Boston, MA USA. RP Poche, RA (reprint author), Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. EM mdickins@bcm.edu RI Sharma, Ramaswamy/F-8401-2012 FU National Institutes of Health [R01EB005173, P20EB0070769]; High Resolution Electron Microscopy Facility, University of Texas, M.D. Anderson Cancer Center [CA16672] FX These studies were supported by funding from the National Institutes of Health R01EB005173 (to MED) and P20EB0070769 (to MED) as well as Institutional Core Grant #CA16672 High Resolution Electron Microscopy Facility, University of Texas, M.D. Anderson Cancer Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 5 Z9 5 U1 0 U2 5 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 JAN 24 PY 2012 VL 7 IS 1 AR e30357 DI 10.1371/journal.pone.0030357 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 910LV UT WOS:000301639600016 PM 22291941 ER PT J AU Merchant, FM Armoundas, AA AF Merchant, Faisal M. Armoundas, Antonis A. TI Role of Substrate and Triggers in the Genesis of Cardiac Alternans, From the Myocyte to the Whole Heart Implications for Therapy SO CIRCULATION LA English DT Article ID T-WAVE ALTERNANS; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; RETICULUM CALCIUM CONTENT; RAT VENTRICULAR MYOCYTES; EFFECTIVE REFRACTORY PERIOD; ACTION-POTENTIAL ALTERNANS; LONG-QT SYNDROME; SARCOPLASMIC-RETICULUM; INTRACELLULAR CALCIUM; RYANODINE RECEPTOR C1 [Armoundas, Antonis A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Armoundas, Antonis A.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Merchant, Faisal M.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Armoundas, AA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM aarmoundas@partners.org FU National Institute of Aging [1R21AG035128]; National Institutes of Health [1RO1HL103961]; Center for Integration of Medicine and Innovative Technology; Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; Cardiovascular Research Society; [0635127N] FX The work was supported by a scientist development grant (#0635127N), by National Institute of Aging grant 1R21AG035128, and by National Institutes of Health grant 1RO1HL103961. This work was also supported by a fellowship and a science award from the Center for Integration of Medicine and Innovative Technology, the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, and the Cardiovascular Research Society. NR 123 TC 17 Z9 17 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 24 PY 2012 VL 125 IS 3 BP 539 EP 549 DI 10.1161/CIRCULATIONAHA.111.033563 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 891YL UT WOS:000300252800022 PM 22271847 ER PT J AU Atashband, A Ramasubbu, K AF Atashband, Armita Ramasubbu, Kumudha TI A Case of a Double Valve SO CIRCULATION LA English DT Editorial Material C1 [Ramasubbu, Kumudha] Baylor Coll Med, Sect Cardiol 3C 330, Michael E DeBakey Med Ctr, Houston, TX 77030 USA. RP Ramasubbu, K (reprint author), Baylor Coll Med, Sect Cardiol 3C 330, Michael E DeBakey Med Ctr, MEDVAMC 111-B,2002 Holcombe Blvd, Houston, TX 77030 USA. EM kumudhar@bcm.edu 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 0009-7322 J9 CIRCULATION JI Circulation PD JAN 24 PY 2012 VL 125 IS 3 BP E272 EP E273 DI 10.1161/CIRCULATIONAHA.111.057240 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 891YL UT WOS:000300252800003 PM 22271851 ER PT J AU Moon, JJ Suh, H Li, AV Ockenhouse, CF Yadava, A Irvine, DJ AF Moon, James J. Suh, Heikyung Li, Adrienne V. Ockenhouse, Christian F. Yadava, Anjali Irvine, Darrell J. TI Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand T-fh cells and promote germinal center induction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PLASMODIUM-VIVAX; CIRCUMSPOROZOITE PROTEIN; ANTIBODY-RESPONSES; SUBCAPSULAR SINUS; EPITOPE DENSITY; B-CELLS; IMMUNOGENICITY; SPOROZOITES; FALCIPARUM; IMMUNITY AB For subunit vaccines, adjuvants play a key role in shaping immunological memory. Nanoparticle (NP) delivery systems for antigens and/or molecular danger signals are promising adjuvants capable of promoting both cellular and humoral immune responses, but in most cases the mechanisms of action of these materials are poorly understood. Here, we studied the immune response elicited by NPs composed of multilamellar "stapled" lipid vesicles carrying a recombinant Plasmodium vivax circumsporozoite antigen, VMP001, both entrapped in the aqueous core and anchored to the lipid bilayer surfaces. Immunization with these particles and monophosphoryl lipid A (MPLA), a US Food and Drug Administration-approved immunostimulatory agonist for Toll-like receptor-4, promoted high-titer, high-avidity antibody responses against VMP001, lasting more than 1 y in mice at 10-fold lower doses than conventional adjuvants. Compared to soluble VMP001 mixed with MPLA, VMP001-NPs promoted broader humoral responses, targeting multiple epitopes of the protein and a more balanced Th1/Th2 cytokine profile from antigen-specific T cells. To begin to understand the underlying mechanisms, we examined components of the B-cell response and found that NPs promoted robust germinal center (GC) formation at low doses of antigen where no GC induction occurred with soluble protein immunization, and that GCs nucleated near depots of NPs accumulating in the draining lymph nodes over time. In parallel, NP vaccination enhanced the expansion of antigen-specific follicular helper T cells (T-fh), compared to vaccinations with soluble VMP001 or alum. Thus, NP vaccines may be a promising strategy to enhance the durability, breadth, and potency of humoral immunity by enhancing key elements of the B-cell response. C1 [Moon, James J.; Suh, Heikyung; Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Moon, James J.; Suh, Heikyung; Li, Adrienne V.; Irvine, Darrell J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Ockenhouse, Christian F.; Yadava, Anjali] Walter Reed Army Inst Res, Div Malaria Vaccine Dev, Silver Spring, MD 20910 USA. [Irvine, Darrell J.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Irvine, Darrell J.] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02129 USA. [Irvine, Darrell J.] Harvard Univ, Boston, MA 02129 USA. [Suh, Heikyung; Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Irvine, DJ (reprint author), MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. EM djirvine@mit.edu FU Ragon Institute of Massachusetts General Hospital; Massachusetts Institute of Technology; Harvard University; Gates Foundation; Department of Defense [W911NF-07-D-0004]; National Institutes of Health [AI095109, 1U19AI091693] FX This work was supported in part by the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University; the Gates Foundation; the Department of Defense (Contract W911NF-07-D-0004); and National Institutes of Health (AI095109 and 1U19AI091693). D.J.I. is an investigator of the Howard Hughes Medical Institute. The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. NR 30 TC 121 Z9 122 U1 4 U2 61 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 JAN 24 PY 2012 VL 109 IS 4 BP 1080 EP 1085 DI 10.1073/pnas.1112648109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 880NA UT WOS:000299412600023 PM 22247289 ER PT J AU Qi, Y Nam, K Spong, MC Banerjee, A Sung, RJ Zhang, M Karplus, M Verdine, GL AF Qi, Yan Nam, Kwangho Spong, Marie C. Banerjee, Anirban Sung, Rou-Jia Zhang, Michael Karplus, Martin Verdine, Gregory L. TI Strandwise translocation of a DNA glycosylase on undamaged DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE disulfide cross-linking; DNA translocation; protein-DNA structure; molecular dynamics simulations ID MOLECULAR-DYNAMICS; REPAIR ENZYME; DAMAGED DNA; INTRAHELICAL LESION; FPG PROTEIN; RECOGNITION; SYSTEM; BASES; CRYSTALLOGRAPHY; 8-OXOGUANINE AB Base excision repair of genotoxic nucleobase lesions in the genome is critically dependent upon the ability of DNA glycosylases to locate rare sites of damage embedded in a vast excess of undamaged DNA, using only thermal energy to fuel the search process. Considerable interest surrounds the question of how DNA glycosylases translocate efficiently along DNA while maintaining their vigilance for target damaged sites. Here, we report the observation of strandwise translocation of 8-oxoguanine DNA glycosylase, MutM, along undamaged DNA. In these complexes, the protein is observed to translocate by one nucleotide on one strand while remaining untranslocated on the complementary strand. We further report that alterations of single base-pairs or a single amino acid substitution (R112A) can induce strandwise translocation. Molecular dynamics simulations confirm that MutM can translocate along DNA in a strandwise fashion. These observations reveal a previously unobserved mode of movement for a DNA-binding protein along the surface of DNA. C1 [Nam, Kwangho; Spong, Marie C.; Banerjee, Anirban; Zhang, Michael; Karplus, Martin; Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Nam, Kwangho; Verdine, Gregory L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Sung, Rou-Jia; Verdine, Gregory L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Karplus, Martin] Univ Strasbourg, Inst Sci & Ingn Supramol, F-67000 Strasbourg, France. [Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Chem Biol Initiat, Boston, MA 02115 USA. [Qi, Yan; Verdine, Gregory L.] Harvard Univ, Sch Med, Program Biophys, Boston, MA 02115 USA. RP Karplus, M (reprint author), Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA. EM marci@tammy.harvard.edu; gregory_verdine@harvard.edu FU National Institutes of Health [GM044853, GM030804]; National Science Foundation; National Cancer Center; Howard Hughes Medical Institute FX This work was supported by National Institutes of Health Grants GM044853, GM044853 (G.L.V.), and GM030804 (M.K.). Y.Q. was supported by a predoctoral fellowship from the National Science Foundation, K.N. by a postdoctoral fellowship from the National Cancer Center, and M.C.S. by a predoctoral fellowship from the Howard Hughes Medical Institute. We thank the staff of the National Synchrotron Light Source and Advanced Photon Source synchrotron facilities. The computational resources are provided by the National Energy Research Scientific Computing Center and Faculty of Arts and Sciences Science Division Research Computing Group at Harvard University. We are grateful to members of the Karplus and Verdine Groups for helpful advice. NR 46 TC 13 Z9 13 U1 1 U2 14 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 JAN 24 PY 2012 VL 109 IS 4 BP 1086 EP 1091 DI 10.1073/pnas.1111237108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 880NA UT WOS:000299412600024 PM 22219368 ER PT J AU Delhase, M Kim, SY Lee, H Naiki-Ito, A Chen, Y Ahn, ER Murata, K Kim, SJ Lautsch, N Kobayashi, KS Shirai, T Karin, M Nakanishi, M AF Delhase, Mireille Kim, Soo-Youl Lee, Ho Naiki-Ito, Aya Chen, Yi Ahn, Eu-Ree Murata, Kazuhiro Kim, Se-Jin Lautsch, Norman Kobayashi, Koichi S. Shirai, Tomoyuki Karin, Michael Nakanishi, Makoto TI TANK-binding kinase 1 (TBK1) controls cell survival through PAI-2/serpinB2 and transglutaminase 2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; tumor necrosis factor signaling; transcriptional; regulation; posttranslational protein modification ID NF-KAPPA-B; ACTIVATOR INHIBITOR TYPE-2; TISSUE TRANSGLUTAMINASE; JNK ACTIVATION; TARGET GENES; IKK-EPSILON; APOPTOSIS; DEATH; TNF; PATHWAY AB The decision between survival and death in cells exposed to TNF relies on a highly regulated equilibrium between proapoptotic and antiapoptotic factors. The TNF-activated antiapoptotic response depends on several transcription factors, including NF-kappa B and its RelA/p65 subunit, that are activated through phosphorylation-mediated degradation of I kappa B inhibitors, a process controlled by the I kappa B kinase complex. Genetic studies in mice have identified the I kappa B kinase-related kinase TANK-binding kinase 1 (TBK1; also called NAK or T2K) as an additional regulatory molecule that promotes survival downstream of TNF, but the mechanism through which TBK1 exerts its survival function has remained elusive. Here we show that TBK1 triggers an antiapoptotic response by controlling a specific RelA/p65 phosphorylation event. TBK1-induced RelA phosphorylation results in inducible expression of plasminogen activator inhibitor-2 (PAI-2), a member of the serpin family with known antiapoptotic activity. PAI-2 limits caspase-3 activation through stabilization of transglutaminase 2 (TG2), which cross-links and inactivates procaspase-3. Importantly, Tg2(-/-) mice were found to be more susceptible to apoptotic cell death in two models of TNF-dependent acute liver injury. Our results establish PAI-2 and TG2 as downstream mediators in the antiapoptotic response triggered upon TBK1 activation. C1 [Delhase, Mireille; Lautsch, Norman; Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. [Delhase, Mireille; Lautsch, Norman; Kobayashi, Koichi S.] Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. [Delhase, Mireille] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Delhase, Mireille; Chen, Yi; Karin, Michael] Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. [Delhase, Mireille; Murata, Kazuhiro; Nakanishi, Makoto] Nagoya City Univ, Dept Cell Biol, Grad Sch Med Sci, Nagoya, Aichi 4678601, Japan. [Kim, Soo-Youl; Ahn, Eu-Ree; Kim, Se-Jin] Natl Canc Ctr, Canc Cell & Mol Biol Branch, Goyang 410769, South Korea. [Lee, Ho] Natl Canc Ctr, Canc Expt Resources Branch, Div Canc Biol, Res Inst, Goyang 410769, South Korea. [Naiki-Ito, Aya; Shirai, Tomoyuki] Nagoya City Univ, Dept Expt Pathol & Tumor Biol, Grad Sch Med Sci, Nagoya, Aichi 4678601, Japan. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. RP Delhase, M (reprint author), Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. EM mdelhase@gmail.com; karinoffice@ucsd.edu FU Claudia Adams Barr Program in Cancer Research; National Institutes of Health (NIH); National Cancer Center (Korea) [NCC 0510270, NCC1110011-1]; National Research Foundation [2010-0029919]; Korean government; NIH [AI043477]; Ministry of Education, Science, Sports, and Culture of Japan; American Cancer Society FX We thank D. Rothwarf for critical reading of the manuscript and helpful suggestions; W.-C. Yeh, S. Akira, A. Beg, A. Hoffmann, R. Flavell, and Z.-W. Li for providing Tbk1-/-, RelA/p65-/-, I kappa B alpha-/-, caspase-3-/-, and Ikk alpha/beta-/- MEFs, respectively; P. Brouckaert for providing mTNF; M. Hernandez (Applied Biosystems) for advice on quantitative PCR; C. H. Jeon for technical assistance; and D. Ginsburg, M. Montminy, T. Kato, and S. Imajoh-Ohmi for plasmids and antibodies. M.D. was supported by a grant from the Claudia Adams Barr Program in Cancer Research. K.S.K. was supported by the National Institutes of Health (NIH). This work was supported by National Cancer Center (Korea) Research Grants NCC 0510270 and NCC1110011-1 (to H.L. and S-Y.K.), National Research Foundation Grant 2010-0029919 funded by the Korean government (to S-Y.K.), NIH Grant AI043477 (to M.K.), and Grants-in-Aid for Scientific Research on Priority Area and for Scientific Research (B) by the Ministry of Education, Science, Sports, and Culture of Japan (M.N.), M.K. is an American Cancer Society Research Professor. NR 51 TC 22 Z9 22 U1 0 U2 2 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 JAN 24 PY 2012 VL 109 IS 4 BP E177 EP E186 DI 10.1073/pnas.1119296109 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 880NA UT WOS:000299412600004 PM 22203995 ER PT J AU Channick, RN Voswinckel, R Rubin, LJ AF Channick, Richard N. Voswinckel, Robert Rubin, Lewis J. TI Inhaled treprostinil: a therapeutic review SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Review DE pulmonary arterial hypertension; prostacyclin; treprostinil; inhaled; nebulizer ID PULMONARY-ARTERIAL-HYPERTENSION; DOUBLE-BLIND; BOSENTAN; SURVIVAL; EFFICACY; TRIAL; PROSTACYCLIN; MULTICENTER; COMBINATION; VOLUNTEERS AB Pulmonary arterial hypertension (PAH) is a life-threatening disease which, if untreated, leads to right ventricular failure and often death. Several effective therapies are now available for PAH, including endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin analogs. The prostacyclin analog treprostinil has proven efficacious when delivered by subcutaneous or intravenous infusion, and most recently by inhalation. Inhaled treprostinil has been shown to be 64%-72% bioavailable in healthy volunteers. Pilot clinical studies have elucidated the acute hemodynamic effects and relative pulmonary selectivity of this agent, as well as established target dosing in PAH and nonoperable chronic thromboembolic PAH. Likewise, chronically administered inhaled treprostinil resulted in clinical and hemodynamic improvement. Both pilot studies confirmed a satisfactory safety profile in patients with PAH. The pivotal Phase III trial, TRIUMPH-I, demonstrated the efficacy and safety of inhaled treprostinil (target dose of 54 mu g four times daily) in PAH patients added to background therapies of bosentan or sildenafil, as assessed by improvements in the primary endpoint, peak six-minute walk distance (median placebo-corrected treatment effect of 20 m), as well as select secondary endpoints. Inhaled treprostinil is approved by the US Food and Drug Administration for patients with World Health Organization Group I PAH to improve exercise ability. Studies establishing effectiveness included predominately patients with New York Heart Association functional class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%). C1 [Channick, Richard N.] Massachusetts Gen Hosp, Pulm Hypertens Program, Boston, MA 02114 USA. [Voswinckel, Robert] Univ Giessen, Dept Internal Med, Lung Ctr, D-6300 Giessen, Germany. [Voswinckel, Robert] Max Planck Inst Heart & Lung Res, Dept Lung Dev & Remodeling, Bad Nauheim, Germany. [Rubin, Lewis J.] Univ Calif San Diego, La Jolla, CA 92093 USA. RP Channick, RN (reprint author), Massachusetts Gen Hosp, Pulm Hypertens Program, Boston, MA 02114 USA. EM rchannick@partners.org RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 32 TC 1 Z9 1 U1 1 U2 6 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-8881 J9 DRUG DES DEV THER JI Drug Des. Dev. Ther. PD JAN 24 PY 2012 VL 6 DI 10.2147/DDDT.S19281 PG 10 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 880EP UT WOS:000299387900001 ER PT J AU Fujiwara, K Hasegawa, K Ohkumo, T Miyoshi, H Tseng, YH Yoshikawa, K AF Fujiwara, Kazushiro Hasegawa, Koichi Ohkumo, Tsuyoshi Miyoshi, Hiroyuki Tseng, Yu-Hua Yoshikawa, Kazuaki TI Necdin Controls Proliferation of White Adipocyte Progenitor Cells SO PLOS ONE LA English DT Article ID PRADER-WILLI-SYNDROME; MOUSE MODEL; STEM-CELLS; PREADIPOCYTE DIFFERENTIATION; POSTMITOTIC NEURONS; GROWTH SUPPRESSOR; SKELETAL-MUSCLE; ADIPOSE-TISSUE; IN-VIVO; GENE AB White adipose tissues are composed mainly of white fat cells adipocytes), which play a key role in energy storage and metabolism. White adipocytes are terminally differentiated postmitotic cells and arise from their progenitor cells (preadipocytes) or mesenchymal stem cells residing in white adipose tissues. Thus, white adipocyte number is most likely controlled by the rate of preadipocyte proliferation, which may contribute to the etiology of obesity. However, little is known about the molecular mechanisms that regulate preadipocyte proliferation during adipose tissue development. Necdin, which is expressed predominantly in postmitotic neurons, is a pleiotropic protein that possesses anti-mitotic and pro-survival activities. Here we show that necdin functions as an intrinsic regulator of white preadipocyte proliferation in developing adipose tissues. Necdin is expressed in early preadipocytes or mesenchymal stem cells residing in the stromal compartment of white adipose tissues in juvenile mice. Lentivirus-mediated knockdown of endogenous necdin expression in vivo in adipose tissues markedly increases fat mass in juvenile mice fed a high-fat diet until adulthood. Furthermore, necdin-null mutant mice exhibit a greater expansion of adipose tissues due to adipocyte hyperplasia than wild-type mice when fed the high-fat diet during the juvenile and adult periods. Adipose stromal-vascular cells prepared from necdin-null mice differentiate in vitro into a significantly larger number of adipocytes in response to adipogenic inducers than those from wild-type mice. These results suggest that necdin prevents excessive preadipocyte proliferation induced by adipogenic stimulation to control white adipocyte number during adipose tissue development. C1 [Fujiwara, Kazushiro; Hasegawa, Koichi; Ohkumo, Tsuyoshi; Yoshikawa, Kazuaki] Osaka Univ, Inst Prot Res, Suita, Osaka 565, Japan. [Miyoshi, Hiroyuki] RIKEN Tsukuba Inst, BioResource Ctr, Tsukuba, Ibaraki, Japan. [Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP Fujiwara, K (reprint author), Osaka Univ, Inst Prot Res, Suita, Osaka 565, Japan. EM yoshikaw@protein.osaka-u.ac.jp RI Miyoshi, Hiroyuki/G-9808-2013 FU Japan Society for the Promotion of Science [21300138] FX This work was supported by a Grant-in-Aid for Scientific Research B2 (21300138) from the Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. NR 48 TC 21 Z9 21 U1 2 U2 3 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 JAN 23 PY 2012 VL 7 IS 1 AR e30948 DI 10.1371/journal.pone.0030948 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 909NE UT WOS:000301570600100 PM 22292082 ER PT J AU Ponnuswamy, P Schrottle, A Ostermeier, E Gruner, S Huang, PL Ertl, G Hoffmann, U Nieswandt, B Kuhlencordt, PJ AF Ponnuswamy, Padmapriya Schroettle, Angelika Ostermeier, Eva Gruener, Sabine Huang, Paul L. Ertl, Georg Hoffmann, Ulrich Nieswandt, Bernhard Kuhlencordt, Peter J. TI eNOS Protects from Atherosclerosis Despite Relevant Superoxide Production by the Enzyme in apoE(-/-) Mice SO PLOS ONE LA English DT Article ID NITRIC-OXIDE SYNTHASE; ENDOTHELIAL CELL-INTERACTIONS; DOUBLE-KNOCKOUT MICE; APOLIPOPROTEIN-E; DEFICIENT MICE; IN-VIVO; ACCELERATED ATHEROSCLEROSIS; LEUKOCYTE ADHESION; PLATELET-ADHESION; LESION FORMATION AB Background: All three nitric oxide synthase (NOS) isoforms are expressed in atherosclerotic plaques. NOS enzymes in general catalyse NO production. However, under conditions of substrate and cofactor deficiency, the enzyme directly catalyse superoxide formation. Considering this alternative chemistry, the effects of NOS on key events in spontaneous hyperlipidemia driven atherosclerosis have not been investigated yet. Here, we evaluate how endothelial nitric oxide synthase (eNOS) modulates leukocyte/endothelial-(L/E) and platelet/endothelial-(P/E) interactions in atherosclerosis and the production of nitric oxide (NO) and superoxide by the enzyme. Principal Findings: Intravital microscopy (IVM) of carotid arteries revealed significantly increased L/E-interactions in apolipoproteinE/eNOS double knockout mice (apoE(-/-)/eNOS(-/-)), while P/E-interactions did not differ, compared to apoE(-/-). eNOS deficiency increased macrophage infiltration in carotid arteries and vascular cell adhesion molecule-1 (VCAM-1) expression, both in endothelial and smooth muscle cells. Despite the expression of other NOS isoforms (inducible NOS, iNOS and neuronal NOS, nNOS) in plaques, Electron Spin Resonance (ESR) measurements of NO showed significant contribution of eNOS to total circulating and vascular wall NO production. Pharmacological inhibition and genetic deletion of eNOS reduced vascular superoxide production, indicating uncoupling of the enzyme in apoE(-/-) vessels. Conclusion: Overt plaque formation, increased vascular inflammation and L/E-interactions are associated with significant reduction of superoxide production in apoE(-/-)/eNOS(-/-) vessels. Therefore, lack of eNOS does not cause an automatic increase in oxidative stress. Uncoupling of eNOS occurs in apoE(-/-) atherosclerosis but does not negate the enzyme's strong protective effects. C1 [Ponnuswamy, Padmapriya; Schroettle, Angelika; Ostermeier, Eva; Ertl, Georg; Kuhlencordt, Peter J.] Univ Wurzburg, Med Klin 1, Herz Kreislaufzentrum, Wurzburg, Germany. [Gruener, Sabine; Nieswandt, Bernhard] Univ Wurzburg, Rudolf Virchow Zentrum Expt Biomed, DFG Res Ctr Expt Biomed, Wurzburg, Germany. [Huang, Paul L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Huang, Paul L.] Harvard Univ, Sch Med, Boston, MA USA. [Schroettle, Angelika; Hoffmann, Ulrich; Kuhlencordt, Peter J.] Univ Munich, Med Poliklin, Div Vasc Med, D-8000 Munich, Germany. RP Ponnuswamy, P (reprint author), INSERM, Paris Cardiovasc Res Ctr, U970, Paris, France. EM peter.kuhlencordt@med.uni-muenchen.de FU Deutsche-Forschungsgemeinschaft [KU-1206(1), KU1206(2)]; Interdisziplinares Zentrum fur Klinische Forschung, Wurzburg [E-30F] FX This work was supported by grants from the Deutsche-Forschungsgemeinschaft [KU-1206(1) and KU1206(2)] and the Interdisziplinares Zentrum fur Klinische Forschung, Wurzburg [E-30F] to PJK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 25 Z9 29 U1 0 U2 1 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 JAN 23 PY 2012 VL 7 IS 1 AR e30193 DI 10.1371/journal.pone.0030193 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 909NE UT WOS:000301570600023 PM 22291917 ER PT J AU Culver, AL Ockene, IS Balasubramanian, R Olendzki, BC Sepavich, DM Wactawski-Wende, J Manson, JE Qiao, YX Liu, SM Merriam, PA Rahilly-Tierny, C Thomas, F Berger, JS Ockene, JK Curb, JD Ma, YS AF Culver, Annie L. Ockene, Ira S. Balasubramanian, Raji Olendzki, Barbara C. Sepavich, Deidre M. Wactawski-Wende, Jean Manson, JoAnn E. Qiao, Yongxia Liu, Simin Merriam, Philip A. Rahilly-Tierny, Catherine Thomas, Fridtjof Berger, Jeffrey S. Ockene, Judith K. Curb, J. David Ma, Yunsheng TI Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women in the Women's Health Initiative SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BASE-LINE CHARACTERISTICS; MRC/BHF HEART PROTECTION; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR EVENTS; CHOLESTEROL LEVELS; SELF-REPORT; MYOCARDIAL-INFARCTION; MULTIETHNIC COHORT; RANDOMIZED-TRIAL; CLINICAL-TRIALS AB Background: This study investigates whether the incidence of new-onset diabetes mellitus (DM) is associated with statin use among postmenopausal women participating in the Women's Health Initiative (WHI). Methods: The WHI recruited 161 808 postmenopausal women aged 50 to 79 years at 40 clinical centers across the United States from 1993 to 1998 with ongoing follow-up. The current analysis includes data through 2005. Statin use was captured at enrollment and year 3. Incident DM status was determined annually from enrollment. Cox proportional hazards models were used to estimate the risk of DM by statin use, with adjustments for propensity score and other potential confounding factors. Subgroup analyses by race/ethnicity, obesity status, and age group were conducted to uncover effect modification. Results: This investigation included 153 840 women without DM and no missing data at baseline. At baseline, 7.04% reported taking statin medication. There were 10 242 incident cases of self-reported DM over 1 004 466 person-years of follow-up. Statin use at baseline was associated with an increased risk of DM(hazard ratio [HR], 1.71; 95% CI, 1.61-1.83). This association remained after adjusting for other potential confounders (multivariate-adjusted HR, 1.48; 95% CI, 1.38-1.59) and was observed for all types of statin medications. Subset analyses evaluating the association of self-reported DM with longitudinal measures of statin use in 125 575 women confirmed these findings. Conclusions: Statin medication use in postmenopausal women is associated with an increased risk for DM. This may be a medication class effect. Further study by statin type and dose may reveal varying risk levels for new-onset DM in this population. C1 [Olendzki, Barbara C.; Sepavich, Deidre M.; Qiao, Yongxia; Merriam, Philip A.; Ockene, Judith K.; Ma, Yunsheng] Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Dept Med, Worcester, MA 01655 USA. [Ockene, Ira S.] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Dept Med, Worcester, MA 01655 USA. [Culver, Annie L.] Mayo Clin, Rochester Methodist Hosp, Rochester, MN USA. [Balasubramanian, Raji] Univ Massachusetts Amherst, Div Biostat & Epidemiol, Amherst, MA USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Qiao, Yongxia] Tongji Univ, Sch Med, Dept Prevent Med, Shanghai 200092, Peoples R China. [Liu, Simin] Univ Calif Los Angeles, Dept Med, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Liu, Simin] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Liu, Simin] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rahilly-Tierny, Catherine] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA USA. [Rahilly-Tierny, Catherine] Brigham & Womens Hosp, Dept Med, Div Aging, Chestnut Hill, MA USA. [Thomas, Fridtjof] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Berger, Jeffrey S.] NYU, Med Ctr, Div Cardiol, Dept Med, New York, NY 10016 USA. [Curb, J. David] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA. RP Ma, YS (reprint author), Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Dept Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM Yunsheng.Ma@umassmed.edu RI Liu, Simin/I-3689-2014; OI Liu, Simin/0000-0003-2098-3844; Olendzki, Barbara/0000-0003-4307-5187; Ma, Yunsheng/0000-0003-2317-3716 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1 R21 DK083700-01A1]; University of Massachusetts Diabetes and Endocrinology Research Center from the NIDDK [5 P30 DK32520]; National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221] FX This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant No. 1 R21 DK083700-01A1 to Dr Ma. It was also supported in part by the University of Massachusetts Diabetes and Endocrinology Research Center grant 5 P30 DK32520 from the NIDDK to Drs Ma and I. S. Ockene. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services, through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. NR 44 TC 196 Z9 207 U1 1 U2 25 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 JAN 23 PY 2012 VL 172 IS 2 BP 144 EP 152 DI 10.1001/archinternmed.2011.625 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 880GF UT WOS:000299392500011 PM 22231607 ER PT J AU Rhee, CM Bhan, I Alexander, EK Brunelli, SM AF Rhee, Connie M. Bhan, Ishir Alexander, Erik K. Brunelli, Steven M. TI Association Between Iodinated Contrast Media Exposure and Incident Hyperthyroidism and Hypothyroidism SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID IODIDE-INDUCED THYROTOXICOSIS; NORMAL THYROID-GLANDS; ALL-CAUSE MORTALITY; SUBCLINICAL HYPOTHYROIDISM; HEART-FAILURE; FOLLOW-UP; RISK; DISEASE; PATIENT; COHORT AB Background: Sudden exposure to high iodide levels may cause thyroid dysfunction. Despite compelling biological plausibility and clinical implication, the association between iodinated contrast media exposure and incident hyperthyroidism and hypothyroidism has not been rigorously studied. Methods: We performed a nested case-control study of patients treated between January 1, 1990, and June 30, 2010, who did not have preexisting hyperthyroidism or hypothyroidism. In parallel analyses, incident hyperthyroid or hypothyroid cases were defined by a change in thyrotropin level from normal (at baseline) to low or high (follow-up measurement). Euthyroid controls were selected using an incidence density sampling approach and were matched to cases on the basis of age, sex, race/ethnicity, estimated glomerular filtration rate, follow-up thyrotropin measurement date, and interval between baseline and the follow-up thyrotropin measurement date. Iodinated contrast media exposure was assessed using claims data for contrast-enhanced computed tomography or cardiac catheterization. Results: In total, 178 and 213 incident hyperthyroid and hypothyroid cases, respectively, were matched to 655 and 779 euthyroid controls, respectively. Iodinated contrast media exposure was associated with incident hyperthyroidism (odds ratio [OR], 1.98; 95% CI, 1.08-3.60), but a statistically significant association with incident hypothyroidism was not observed (OR, 1.58; 95% CI, 0.952.62). In prespecified secondary analysis, iodinated contrast media exposure was associated with incident overt hyperthyroidism (follow-up thyrotropin level <= 0.1 mIU/L; OR, 2.50; 95% CI, 1.06-5.93) and with incident overt hypothyroidism (follow-up thyrotropin level >10 mIU/L; OR, 3.05; 95% CI, 1.07-8.72). Conclusion: Iodinated contrast media exposure is associated with subsequent development of incident hyperthyroidism and incident overt hypothyroidism. C1 [Rhee, Connie M.; Brunelli, Steven M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Renal Div, Boston, MA 02115 USA. [Alexander, Erik K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Endocrinol Diabet & Hypertens Div,Dept Med, Boston, MA 02115 USA. [Brunelli, Steven M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Pharmacoepidemiol Div,Dept Med, Boston, MA 02115 USA. [Bhan, Ishir] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Renal,Dept Med, Boston, MA 02115 USA. RP Brunelli, SM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Renal Div, 75 Francis St,Ste MRB-4, Boston, MA 02115 USA. EM sbrunelli@partners.org FU Veracyte, Inc; Asuragen, Inc.; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [DK007527-26, DK079056] FX Dr Alexander receives research support from Veracyte, Inc, and Asuragen, Inc.; This work was supported by grants DK007527-26 (Dr Rhee) and DK079056 (Dr Brunelli) from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 49 TC 61 Z9 64 U1 1 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 JAN 23 PY 2012 VL 172 IS 2 BP 153 EP 159 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 880GF UT WOS:000299392500013 PM 22271121 ER PT J AU Secemsky, EA Lange, D Ho, JE Brayton, K Ganz, PA Farr, G MacGregor, JS Hsue, PY AF Secemsky, Eric A. Lange, David Ho, Jennifer E. Brayton, Kimberly Ganz, Peter A. Farr, Genevieve MacGregor, John S. Hsue, Priscilla Y. TI Improvement in Revascularization Time After Creation of a Coronary Catheterization Laboratory at a Public Hospital SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID ELEVATION MYOCARDIAL-INFARCTION; CARDIOVASCULAR DATA REGISTRY; TO-BALLOON TIMES; INTERHOSPITAL TRANSFER; PRIMARY ANGIOPLASTY; NATIONAL-REGISTRY; INTERVENTION; MORTALITY; REPERFUSION C1 [Ho, Jennifer E.; Ganz, Peter A.; Farr, Genevieve; Hsue, Priscilla Y.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. [Secemsky, Eric A.; Lange, David; Brayton, Kimberly] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Internal Med, San Francisco, CA 94110 USA. [Ho, Jennifer E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Hsue, PY (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, 1001 Potrero Ave,Room 5G1, San Francisco, CA 94110 USA. EM phsue@medsfgh.ucsf.edu OI Ho, Jennifer/0000-0002-7987-4768 NR 9 TC 1 Z9 1 U1 0 U2 0 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 JAN 23 PY 2012 VL 172 IS 2 BP 193 EP 194 DI 10.1001/archinternmed.2011.564 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 880GF UT WOS:000299392500026 PM 22123753 ER PT J AU Schuetz, P Briel, M Chiappa, V Greenwald, JL AF Schuetz, Philipp Briel, Matthias Chiappa, Victor Greenwald, Jeffrey L. TI Do Procalcitonin Algorithms Modify Mortality? reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID RESPIRATORY-TRACT INFECTIONS; RANDOMIZED CONTROLLED-TRIAL; ANTIBIOTIC USE; CARE C1 [Schuetz, Philipp] Harvard Univ, Sch Publ Hlth, Dept Emergency, Boston, MA 02115 USA. [Briel, Matthias] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Chiappa, Victor; Greenwald, Jeffrey L.] Massachusetts Gen Hosp, Dept Med, Inpatient Clinician Educ Serv, Boston, MA 02114 USA. RP Schuetz, P (reprint author), Harvard Univ, Sch Publ Hlth, Dept Emergency, 667 Huntington Ave, Boston, MA 02115 USA. EM philipp.schuetz@post.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 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 JAN 23 PY 2012 VL 172 IS 2 BP 198 EP 198 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 880GF UT WOS:000299392500034 ER PT J AU Larauche, M Mulak, A Yuan, PQ Kanauchi, O Tache, Y AF Larauche, Muriel Mulak, Agata Yuan, Pu-Qing Kanauchi, Osamu Tache, Yvette TI Stress-induced visceral analgesia assessed non-invasively in rats is enhanced by prebiotic diet SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Stress-related visceral analgesia; Water avoidance stress; Colorectal distension; Enzyme-treated rice fiber prebiotic; Short chain fatty acids; Defecation; Rat; Solid-state manometry ID IRRITABLE-BOWEL-SYNDROME; CORTICOTROPIN-RELEASING-FACTOR; CHAIN FATTY-ACIDS; EPITHELIAL BARRIER DYSFUNCTION; CHRONIC PSYCHOLOGICAL STRESS; WATER-AVOIDANCE STRESS; COLORECTAL DISTENSION; COLONIC HYPERSENSITIVITY; BACTERIAL TRANSLOCATION; RECEPTORS MEDIATE AB AIM: To investigate the influence of repeated water avoidance stress (rWAS) on the visceromotor response (VMR) to colorectal distension (CRD) and the modulation of the response by a prebiotic diet in rats using a novel surgery-free method of solid-state manometry. METHODS: Male Wistar rats fed a standard diet with or without 4% enzyme-treated rice fiber (ERF) for 5 wk were subjected to rWAS (1 h daily x 10 d) or no stress. The VMR to graded phasic CRD was assessed by intraluminal colonic pressure recording on days 0 (baseline), 1 and 10 (45 min) and 11 (24 h) after rWAS and expressed as percentage change from baseline. Cecal content of short chain fatty acids and distal colonic histology were assessed on day 11. RESULTS: WAS on day 1 reduced the VMR to CRD at 40 and 60 mmHg similarly by 28.9% +/- 6.6% in both diet groups. On day 10, rWAS-induced reduction of VMR occurred only at 40 mmHg in the standard diet group (36.2% +/- 17.8%) while in the ERF group VMR was lowered at 20, 40 and 60 mmHg by 64.9% +/- 20.9%, 49.3% +/- 11.6% and 38.9% +/- 7.3% respectively. The visceral analgesia was still observed on day 11 in ERF- but not in standard diet-fed rats. By contrast the non-stressed groups (standard or ERF duet) exhibited no changes in VMR to CRD. In standard diet-fed rats, rWAS induced mild colonic histological changes that were absent in ERF-fed rats exposed to stress compared to non-stressed rats. The reduction of cecal content of isobutyrate and total butyrate, but not butyrate alone, was correlated with lower visceral pain response. Additionally, ERF diet increased rWAS-induced defecation by 26% and 75% during the first 0-15 min and last 15-60 min, respectively, compared to standard diet, and reduced rats' body weight gain by 1.3 fold independently of their stress status. CONCLUSION: These data provide the first evidence of psychological stress-related visceral analgesia in rats that was enhanced by chronic intake of ERF prebiotic. (C) 2012 Baishideng. All rights reserved. C1 [Larauche, Muriel; Yuan, Pu-Qing; Tache, Yvette] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Larauche, Muriel; Yuan, Pu-Qing; Tache, Yvette] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Oppenheimer Family Ctr Neurobiol Stress, Dept Med,Digest Dis Div, Los Angeles, CA 90073 USA. [Mulak, Agata] Wroclaw Med Univ, Dept Gastroenterol & Hepatol, PL-50556 Wroclaw, Poland. [Kanauchi, Osamu] Shiga Univ Med Sci, Shiga, Japan. [Kanauchi, Osamu] Kirin Holdings Co Ltd, Cent Labs Frontier Technol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. RP Larauche, M (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, 11301 Wilshire Blvd,CURE Bldg 115,Room 111, Los Angeles, CA 90073 USA. EM mlarauche@mednet.ucla.edu OI Larauche, Muriel/0000-0003-3320-3675 FU Central Labs for Frontier Technology Kirin Holdings Co., Ltd Japan; National Institute of Health [P50 DK-64539, DK-41301, R01 DK-33061]; Veterans Administration FX Supported by Central Labs for Frontier Technology Kirin Holdings Co., Ltd Japan and the National Institute of Health grants, P50 DK-64539 (to Tache Y and Larauche M), Center Grant DK-41301 (Animal Core, to Yvette Tache), R01 DK-33061 (to Yvette Tache); and Veterans Administration Research Career Scientist Award NR 67 TC 11 Z9 11 U1 0 U2 3 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 JAN 21 PY 2012 VL 18 IS 3 BP 225 EP 236 DI 10.3748/wjg.v18.i3.225 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 887XK UT WOS:000299965000004 PM 22294825 ER PT J AU Thompson, BT AF Thompson, B. Taylor TI beta-agonists for ARDS: the dark side of adrenergic stimulation? SO LANCET LA English DT Editorial Material ID ACUTE LUNG INJURY; CONTROLLED CLINICAL-TRIAL C1 [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Thompson, B. Taylor] Harvard Univ, Sch Med, Boston, MA USA. RP Thompson, BT (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. EM tthompson1@partners.org NR 14 TC 3 Z9 4 U1 0 U2 1 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 JAN 21 PY 2012 VL 379 IS 9812 BP 196 EP 198 DI 10.1016/S0140-6736(11)61845-X PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 879FW UT WOS:000299316100012 PM 22166901 ER PT J AU Moteabbed, M Geyer, A Drenkhahn, R Bolch, WE Paganetti, H AF Moteabbed, Maryam Geyer, Amy Drenkhahn, Robert Bolch, Wesley E. Paganetti, Harald TI Comparison of whole-body phantom designs to estimate organ equivalent neutron doses for secondary cancer risk assessment in proton therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID PEDIATRIC-PATIENTS; VOXEL PHANTOMS; BEAM THERAPY; RADIOTHERAPY; DOSIMETRY; ADULT; AGE AB Secondary neutron fluence created during proton therapy can be a significant source of radiation exposure in organs distant from the treatment site, especially in pediatric patients. Various published studies have used computational phantoms to estimate neutron equivalent doses in proton therapy. In these simulations, whole-body patient representations were applied considering either generic whole-body phantoms or generic age-and gender-dependent phantoms. No studies to date have reported using patient-specific geometry information. The purpose of this study was to estimate the effects of patient-phantom matching when using computational pediatric phantoms. To achieve this goal, three sets of phantoms, including different ages and genders, were compared to the patients' whole-body CT. These sets consisted of pediatric age-specific reference, age-adjusted reference and anatomically sculpted phantoms. The neutron equivalent dose for a subset of out-of-field organs was calculated using the GEANT4 Monte Carlo toolkit, where proton fields were used to irradiate the cranium and the spine of all phantoms and the CT-segmented patient models. The maximum neutron equivalent dose per treatment absorbed dose was calculated and found to be on the order of 0 to 5 mSv Gy(-1). The relative dose difference between each phantom and their respective CT-segmented patient model for most organs showed a dependence on how close the phantom and patient heights were matched. The weight matching was found to have much smaller impact on the dose accuracy except for very heavy patients. Analysis of relative dose difference with respect to height difference suggested that phantom sculpting has a positive effect in terms of dose accuracy as long as the patient is close to the 50th percentile height and weight. Otherwise, the benefit of sculpting was masked by inherent uncertainties, i.e. variations in organ shapes, sizes and locations. Other sources of uncertainty included errors associated with beam positioning, neutron weighting factor definition and organ segmentation. This work demonstrated the importance of hybrid phantom height matching for more accurate organ dose calculation in proton therapy and the potential limitations of reference phantoms released by regulatory bodies for radiation therapy applications. C1 [Moteabbed, Maryam; Drenkhahn, Robert; Paganetti, Harald] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moteabbed, Maryam; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Geyer, Amy; Bolch, Wesley E.] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA. RP Moteabbed, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mmoteabbed@partners.org FU NCI [C06 CA059267] FX This work was supported by the NCI: Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267. NR 29 TC 3 Z9 3 U1 1 U2 11 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2012 VL 57 IS 2 BP 499 EP 515 DI 10.1088/0031-9155/57/2/499 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 877HU UT WOS:000299169200015 PM 22217682 ER PT J AU Malempati, S Weigel, B Ingle, AM Ahern, CH Carroll, JM Roberts, CT Reid, JM Schmechel, S Voss, SD Cho, SY Chen, HX Krailo, MD Adamson, PC Blaney, SM AF Malempati, Suman Weigel, Brenda Ingle, Ashish M. Ahern, Charlotte H. Carroll, Julie M. Roberts, Charles T. Reid, Joel M. Schmechel, Stephen Voss, Stephan D. Cho, Steven Y. Chen, Helen X. Krailo, Mark D. Adamson, Peter C. Blaney, Susan M. TI Phase I/II Trial and Pharmacokinetic Study of Cixutumumab in Pediatric Patients With Refractory Solid Tumors and Ewing Sarcoma: A Report From the Children's Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FACTOR-I-RECEPTOR; GROWTH-FACTOR RECEPTOR; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; CLINICAL-TRIALS; DOWN-REGULATION; BREAST-CANCER; FACTOR SYSTEM; WILMS-TUMOR; INSULIN AB Purpose A phase I/II study of cixutumumab (IMC-A12) in children with refractory solid tumors was conducted. This study was designed to assess the toxicities, pharmacokinetics, and pharmacodynamics of cixutumumab in children to determine a recommended phase II dose and to assess antitumor activity in Ewing sarcoma (ES). Patients and Methods Pediatric patients with relapsed or refractory solid tumors were treated with cixutumumab as a 1-hour intravenous infusion once per week. Two dose levels-6 and 9 mg/kg-were evaluated using a standard three-plus-three cohort design. Patients with refractory ES were treated in an expanded phase II cohort at each dose level. Results Forty-seven eligible patients with a median age of 15 years (range, 4 to 28 years) were enrolled. Twelve patients were treated in the dose-finding phase. Hematologic and nonhematologic toxicities were generally mild and infrequent. Dose-limiting toxicities included grade 4 thrombocytopenia at 6 mg/kg and grade 3 dehydration at 9 mg/kg. Mean trough concentration (+/- standard deviation) at 9 mg/kg was 106 +/- 57 mu g/mL, which exceeded the effective trough concentration of 60 mu g/mL observed in xenograft models. Three patients with ES had confirmed partial responses: one of 10 at 6 mg/kg and two of 20 at 9 mg/kg. Serum insulin-like growth factor I (IGF-I) levels consistently increased after one dose of cixutumumab. Tumor IGF-I receptor expression by immunohistochemistry did not correlate with response in patients with ES. Conclusion Cixutumumab is well tolerated in children with refractory solid tumors. The recommended phase II dose is 9 mg/kg. Limited single-agent activity of cixutumumab was seen in ES. C1 [Malempati, Suman] Oregon Hlth & Sci Univ, Dept Pediat, CDRC P, Portland, OR 97239 USA. [Carroll, Julie M.; Roberts, Charles T.] Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Weigel, Brenda; Schmechel, Stephen] Univ Minnesota, Minneapolis, MN USA. [Ingle, Ashish M.; Krailo, Mark D.] Childrens Oncol Grp Operat Ctr, Arcadia, CA USA. [Ahern, Charlotte H.; Blaney, Susan M.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Reid, Joel M.] Mayo Clin & Mayo Fdn, Rochester, MN USA. [Voss, Stephan D.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cho, Steven Y.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Chen, Helen X.] NCI, Rockville, MD USA. [Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Malempati, S (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, CDRC P, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM malempat@ohsu.edu OI Roberts, Charles/0000-0003-1756-5772 FU National Cancer Institute [U01 CA97452, U10 CA98543]; General Clinical Research Center [M01-RR00188-46] FX Supported by National Cancer Institute Grants No. U01 CA97452 and U10 CA98543 and General Clinical Research Center Grant No. M01-RR00188-46. NR 38 TC 68 Z9 70 U1 0 U2 7 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 JAN 20 PY 2012 VL 30 IS 3 BP 256 EP 262 DI 10.1200/JCO.2011.37.4355 PG 7 WC Oncology SC Oncology GA 923LG UT WOS:000302620200012 PM 22184397 ER PT J AU Bendell, JC Rodon, J Burris, HA de Jonge, M Verweij, J Birle, D Demanse, D De Buck, SS Ru, QHC Peters, M Goldbrunner, M Baselga, J AF Bendell, Johanna C. Rodon, Jordi Burris, Howard A. de Jonge, Maja Verweij, Jaap Birle, Diana Demanse, David De Buck, Stefan S. Ru, Qinhua C. Peters, Malte Goldbrunner, Michael Baselga, Jose TI Phase I, Dose-Escalation Study of BKM120, an Oral Pan-Class I PI3K Inhibitor, in Patients With Advanced Solid Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER; PROSTATE-CANCER; BREAST-CANCER; PIK3CA GENE; KINASE-B; PATHWAY; RESISTANCE; NVP-BEZ235 AB Purpose This phase I dose-escalation study investigated the maximum-tolerated dose (MTD), safety, preliminary activity, pharmacokinetics (PK), and pharmacodynamics of BKM120, a potent and highly specific oral pan-Class I PI3K inhibitor. Patients and Methods Thirty-five patients with advanced solid tumors received daily BKM120 12.5 to 150 mg. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Assessments included archival tumor molecular status, response by Response Evaluation Criteria in Solid Tumors (RECIST), positron emission tomography tracer uptake ([F-18] fluorodeoxyglucose positron emission tomography [FDG-PET]), fasting plasma C-peptide, and phosphorylated ribosomal protein S6 (pS6) in skin biopsies. Results Overall, treatment was well tolerated. Dose-limiting toxicities were grade 2 mood alteration (80 mg), grade 3 epigastralgia, grade 3 rash, grade 2 and grade 3 mood alteration (100 mg), and two grade 4 hyperglycemia (150 mg). The MTD was 100 mg/d. Frequent treatment-related adverse events included rash, hyperglycemia, diarrhea, anorexia, and mood alteration (37% each); nausea (31%); fatigue (26%); pruritus (23%); and mucositis (23%). BKM120 demonstrated rapid absorption, half-life of similar to 40 hours, similar to three-fold steady-state accumulation, dose-proportional exposure, and moderate interpatient variability. One patient demonstrated a confirmed partial response (triple-negative breast cancer); seven patients (20%) were on study for >= 8 months. BKM120 demonstrated dose-dependent pharmacodynamic effects on [F-18] FDG-PET, fasting C-peptide, fasting blood glucose, and pS6. No significant trends were seen to correlate tumor molecular alterations with clinical activity. Conclusion This study demonstrates feasibility and proof-of-concept of class I PI3K inhibition in patients with advanced cancers. BKM120, at the MTD of 100 mg/d, is safe and well tolerated, with a favorable PK profile, clear evidence of target inhibition, and preliminary antitumor activity. C1 [Bendell, Johanna C.; Burris, Howard A.] Sarah Cannon Res Inst, Nashville, TN USA. [Rodon, Jordi; Baselga, Jose] Vall dHebron Univ Hosp, Barcelona, Spain. [de Jonge, Maja; Verweij, Jaap] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Birle, Diana] Novartis Inst Biomed Res, Cambridge, MA USA. [Demanse, David; De Buck, Stefan S.; Peters, Malte; Goldbrunner, Michael] Novartis Pharmaceut, Basel, Switzerland. [Ru, Qinhua C.] Novartis Oncol, Florham Pk, NJ USA. RP Baselga, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House 108, Boston, MA 02114 USA. EM jbaselga@partners.org FU Novartis Pharma, Basel, Switzerland FX Supported by Novartis Pharma, Basel, Switzerland. NR 40 TC 278 Z9 283 U1 2 U2 21 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 JAN 20 PY 2012 VL 30 IS 3 BP 282 EP 290 DI 10.1200/JCO.2011.36.1360 PG 9 WC Oncology SC Oncology GA 923LG UT WOS:000302620200016 PM 22162589 ER PT J AU Sprauten, M Darrah, TH Peterson, DR Campbell, ME Hannigan, RE Cvancarova, M Beard, C Haugnes, HS Fossa, SD Oldenburg, J Travis, LB AF Sprauten, Mette Darrah, Thomas H. Peterson, Derick R. Campbell, M. Ellen Hannigan, Robyn E. Cvancarova, Milada Beard, Clair Haugnes, Hege S. Fossa, Sophie D. Oldenburg, Jan Travis, Lois B. TI Impact of Long-Term Serum Platinum Concentrations on Neuro- and Ototoxicity in Cisplatin-Treated Survivors of Testicular Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GERM-CELL-CANCER; COUNCIL EUROPEAN ORGANIZATION; PLASMA-MASS SPECTROMETRY; CARDIOVASCULAR-DISEASE; RANDOMIZED-TRIAL; OVARIAN-CANCER; RISK-FACTORS; CHEMOTHERAPY; CARBOPLATIN; PROGNOSIS AB Purpose Cisplatin-induced neurotoxicity and ototoxicity (NTX) are important adverse effects after chemotherapy for testicular cancer (TC). Although serum platinum is measurable years after therapy, its impact on NTX has not been evaluated. Patients and Methods In all, 169 cisplatin-treated survivors of TC provided blood samples at Survey I and reported NTX during Survey I (1998-2002) and Survey II (2007-2008). Serum platinum was quantified by inductively coupled plasma mass spectrometry. Patient-reported outcomes were evaluated with the Scale for Chemotherapy-Induced Neurotoxicity (SCIN), regarding the extent of symptom bother as 0, "not at all"; 1, "a little"; 2, "quite a bit"; or 3, "very much." Summing the six symptom scores yielded a total SCIN score of 0 to 18. Categorizing total SCIN scores into quartiles yielded similar-sized groups with increasing symptoms. Multivariate ordinal logistic regression analyses evaluated associations between NTX and long-term serum platinum levels, adjusting for cisplatin dose, dosing schedule, and age. Results At Survey I, a significant four-to five-fold association with total SCIN score emerged for the highest serum platinum quartile (odds ratio [OR], 4.69; 95% CI, 1.82 to 12.08). Paresthesias and Raynaud's syndrome (hands and feet) showed significant two-to four-fold increased risks with the highest platinum quartile. At Survey II, total SCIN score remained significantly associated with the highest platinum quartile (OR, 4.28; 95% CI, 1.36 to 13.48). Paresthesias (hands and feet) and tinnitus showed significant three-to four-fold increased risks for the highest platinum quartile. Cumulative cisplatin dose was not associated with total SCIN score or individual SCIN symptoms in multivariate analyses. Conclusion Here we document a significant relationship between increasing levels of residual serum platinum and NTX severity after adjusting for initial cisplatin dose. C1 [Fossa, Sophie D.] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Clin Canc Res, N-0424 Oslo, Norway. [Haugnes, Hege S.] Univ Tromso, Tromso, Norway. [Haugnes, Hege S.] Univ Hosp N Norway, Tromso, Norway. [Darrah, Thomas H.; Campbell, M. Ellen; Hannigan, Robyn E.] Univ Massachusetts, Boston, MA 02125 USA. [Beard, Clair] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Peterson, Derick R.; Travis, Lois B.] Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. RP Fossa, SD (reprint author), Oslo Univ Hosp, Norwegian Radium Hosp, Dept Clin Canc Res, Postboks 4953 Nydalen, N-0424 Oslo, Norway. EM s.d.fossa@medisin.uio.no RI Hannigan, Robyn /F-8628-2010; Darrah, Tom/I-2253-2016 OI Hannigan, Robyn /0000-0003-4782-1124; FU National Center for Research Resources of the National Institutes of Health [1 UL1 RR024160-01]; National Institutes of Health [5U56CA118635]; South-Eastern Norway Regional Health Authority [39247] FX Supported by Grants No. 1 UL1 RR024160-01 (L.B.T.) from the National Center for Research Resources of the National Institutes of Health, No. 5U56CA118635 (T.H.D., R.E.H., and C.B.) from the National Institutes of Health, and No. 39247 (M.S.) from the South-Eastern Norway Regional Health Authority. NR 64 TC 43 Z9 43 U1 0 U2 12 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 JAN 20 PY 2012 VL 30 IS 3 BP 300 EP 307 DI 10.1200/JCO.2011.37.4025 PG 8 WC Oncology SC Oncology GA 923LG UT WOS:000302620200018 PM 22184390 ER PT J AU Oberholzer, PA Kee, D Dziunycz, P Sucker, A Kamsukom, N Jones, R Roden, C Chalk, CJ Ardlie, K Palescandolo, E Piris, A MacConaill, LE Robert, C Hofbauer, GFL McArthur, GA Schadendorf, D Garraway, LA AF Oberholzer, Patrick A. Kee, Damien Dziunycz, Piotr Sucker, Antje Kamsukom, Nyam Jones, Robert Roden, Christine Chalk, Clinton J. Ardlie, Kristin Palescandolo, Emanuele Piris, Adriano MacConaill, Laura E. Robert, Caroline Hofbauer, Guenther F. L. McArthur, Grant A. Schadendorf, Dirk Garraway, Levi A. TI RAS Mutations Are Associated With the Development of Cutaneous Squamous Cell Tumors in Patients Treated With RAF Inhibitors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NONMELANOMA SKIN CANCERS; ACTINIC KERATOSIS; GENE-MUTATIONS; MELANOMA; BRAF; SORAFENIB; CARCINOMA; PATHWAY; KERATOACANTHOMA; PROGRESSION AB Purpose RAF inhibitors are effective against melanomas with BRAF V600E mutations but may induce keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cSCCs). The potential of these agents to promote secondary malignancies is concerning. We analyzed cSCC and KA lesions for genetic mutations in an attempt to identify an underlying mechanism for their formation. Methods Four international centers contributed 237 KA or cSCC tumor samples from patients receiving an RAF inhibitor (either vemurafenib or sorafenib; n = 19) or immunosuppression therapy (n = 53) or tumors that developed spontaneously (n = 165). Each sample was profiled for 396 known somatic mutations across 33 cancer-related genes by using a mass spectrometric-based genotyping platform. Results Mutations were detected in 16% of tumors (38 of 237), with five tumors harboring two mutations. Mutations in TP53, CDKN2A, HRAS, KRAS, and PIK3CA were previously described in squamous cell tumors. Mutations in MYC, FGFR3, and VHL were identified for the first time. A higher frequency of activating RAS mutations was found in tumors from patients treated with an RAF inhibitor versus populations treated with a non-RAF inhibitor (21.1% v 3.2%; P < .01), although overall mutation rates between treatment groups were similar (RAF inhibitor, 21.1%; immunosuppression, 18.9%; and spontaneous, 17.6%; P = not significant). Tumor histology (KA v cSCC), tumor site (head and neck v other), patient age (<= 70 v >70 years), and sex had no significant impact on mutation rate or type. Conclusion Squamous cell tumors from patients treated with an RAF inhibitor have a distinct mutational profile that supports a mechanism of therapy-induced tumorigenesis in RAS-primed cells. Conceivably, cotargeting of MEK together with RAF may reduce or prevent formation of these tumors. C1 [Oberholzer, Patrick A.; Chalk, Clinton J.; Ardlie, Kristin; MacConaill, Laura E.; Garraway, Levi A.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Oberholzer, Patrick A.; Jones, Robert; Roden, Christine; Palescandolo, Emanuele; MacConaill, Laura E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Piris, Adriano] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Piris, Adriano] Harvard Univ, Sch Med, Boston, MA USA. [Kee, Damien; McArthur, Grant A.] Peter MacCallum Canc Ctr, Melbourne, Australia. [Kee, Damien] Univ Melbourne, Parkville, Vic 3052, Australia. [Dziunycz, Piotr; Hofbauer, Guenther F. L.] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. [Sucker, Antje; Schadendorf, Dirk] Univ Hosp Essen, Essen, Germany. [Kamsukom, Nyam; Robert, Caroline] Inst Gustave Roussy, Villejuif, France. [Kamsukom, Nyam; Robert, Caroline] INSERM, U981, Villejuif, France. RP Garraway, LA (reprint author), Broad Inst MIT & Harvard, Dana Bldg,Room 1542,44 Binney St, Boston, MA 02115 USA. EM levi_garraway@dfci.harvard.edu RI Hofbauer, Gunther/B-2671-2010 OI Hofbauer, Gunther/0000-0003-0542-7989 FU National Institutes of Health, National Cancer Institute [DP2OD002750, R33CA126674]; Starr Cancer Consortium; Melanoma Research Alliance; Swiss National Science Foundation [PASMP3-127676/1]; Novartis FX Supported by Grants No. DP2OD002750 and R33CA126674 from the National Institutes of Health, National Cancer Institute; by the Starr Cancer Consortium; by the Melanoma Research Alliance (L.A.G.); and by Grant No. PASMP3-127676/1 from the Swiss National Science Foundation (P.A.O. and L.A.G.).; Research Funding: Levi A. Garraway, Novartis NR 46 TC 198 Z9 204 U1 2 U2 23 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 JAN 20 PY 2012 VL 30 IS 3 BP 316 EP 321 DI 10.1200/JCO.2011.36.7680 PG 6 WC Oncology SC Oncology GA 923LG UT WOS:000302620200020 PM 22067401 ER PT J AU de Groot, JF Heimberger, A Prados, MD Wen, PY AF de Groot, John F. Heimberger, Amy Prados, Michael D. Wen, Patrick Y. TI Maximizing the Efficacy of Angiogenesis Inhibitors Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CELLS; CANCER; GLIOMA C1 [de Groot, John F.; Heimberger, Amy] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Prados, Michael D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP de Groot, JF (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 12 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2012 VL 30 IS 3 BP 338 EP 339 DI 10.1200/JCO.2011.38.6680 PG 3 WC Oncology SC Oncology GA 923LG UT WOS:000302620200029 ER PT J AU Chi, AS Batchelor, TT Kwak, EL Clark, JW Wang, DL Wilner, KD Louis, DN Iafrate, AJ AF Chi, Andrew S. Batchelor, Tracy T. Kwak, Eunice L. Clark, Jeffrey W. Wang, Daphne L. Wilner, Keith D. Louis, David N. Iafrate, A. John TI Rapid Radiographic and Clinical Improvement After Treatment of a MET-Amplified Recurrent Glioblastoma With a Mesenchymal-Epithelial Transition Inhibitor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FACTOR/HEPATOCYTE GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; C-MET; ANAPLASTIC LYMPHOMA; EXPRESSION; AMPLIFICATION; TUMORS; PF-2341066; CRIZOTINIB C1 [Chi, Andrew S.; Batchelor, Tracy T.; Kwak, Eunice L.; Clark, Jeffrey W.; Wang, Daphne L.; Louis, David N.; Iafrate, A. John] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Wilner, Keith D.] Pfizer, New York, NY USA. RP Chi, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. FU Pfizer FX Research Funding: Andrew S. Chi, Pfizer; Tracy T. Batchelor, Pfizer; Eunice L. Kwak, Pfizer; Jeffrey W. Clark, Pfizer NR 30 TC 37 Z9 39 U1 0 U2 4 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 JAN 20 PY 2012 VL 30 IS 3 BP E30 EP E33 DI 10.1200/JCO.2011.38.4586 PG 4 WC Oncology SC Oncology GA 923LG UT WOS:000302620200003 PM 22162573 ER PT J AU Ahmed, FK Clark, BE Burton, DR Pantophlet, R AF Ahmed, Fatima K. Clark, Brenda E. Burton, Dennis R. Pantophlet, Ralph TI An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site SO VACCINE LA English DT Article DE Protein engineering; b12; Hyperglycosylation; lmmunofocusing ID IMMUNODEFICIENCY-VIRUS TYPE-1; B-CELL RESPONSES; BROADLY NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; HIV-1-INFECTED INDIVIDUALS; SHIV CHALLENGE; VACCINE DESIGN; EPITOPE; CD4 AB A major priority in HIV vaccine research is the development of an immunogen to elicit broadly neutralizing antibodies (NAbs). Monoclonal antibody (mAb) b12 is one of now several broadly neutralizing mAbs that bind epitopes overlapping the CD4-binding site (CD4bs) on HIV-1 gpl 20 and that serve as templates to engineer effective immunogens. We are exploring a strategy whereby extra glycans are incorporated onto gp120 to occlude the epitopes of non-neutralizing mAbs while maintaining exposure of the b12 site. Immunizing with these so-called hyperglycosylated gp120s is hypothesized to preferentially elicit b12-like NAbs. Here, the effects of two adjuvants, monophosphoryl lipid A (MPL) and Quil A, on eliciting b12-like responses when formulated with a new hyperglycosylated mutant, Delta N2mCHO(Q105N), is presented. Sera from Delta N2mCHO(Q105N)_MPL immunized animals bound the homologous antigen Delta N2mCHO(Q105N) with greater preference than sera from Delta N2mCHO(Q105N)_QuilA immunized animals, demonstrating the modulation of antibody fine specificity by these two adjuvants. We also found that sera from Delta N2mCHO(Q105N)_QuilA immunized animals bound best to a resurfaced HIV gpl 20 core protein on which non-CD4bs epitopes are substituted with non-HIV residues, suggesting that these sera contain a relatively larger fraction of CD4bs-specific antibodies. Consistent with these data, inhibition assays revealed epitope overlap with the binding sites of the CD4bs-specific antibodies b12, b13 and VRCO3. Unexpectedly, these sera did not exhibit significant neutralizing activity against a set of HIV-1 primary strains. Our results show that although formulating mutant Delta N2mCHO(Q105N) with Quil A promotes the elicitation of CD4bs-directed antibodies relative to wild-type gp120, tweaking of the immunization regimen is needed to yield robust, CD4bs-focused NAbs. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Clark, Brenda E.; Pantophlet, Ralph] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Ahmed, Fatima K.; Pantophlet, Ralph] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. [Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Burton, Dennis R.] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02129 USA. [Burton, Dennis R.] Harvard Univ, Boston, MA 02129 USA. RP Pantophlet, R (reprint author), Simon Fraser Univ, Fac Hlth Sci, Blusson Hall,8888 Univ Dr, Burnaby, BC V5A 1S6, Canada. EM rpantophlet@sfu.ca FU CIHR [200100]; Canada Foundation for Innovation; British Columbia Knowledge Development Fund; IAVI Neutralizing Antibody Consortium; NIH [A133292, A160425] FX Financial support for this study was provided by CIHR operating grant 200100 and a CIHR New Investigator Award (to R.P.) and infrastructure development funding from the Canada Foundation for Innovation and the British Columbia Knowledge Development Fund (to R.P.). Financial support for some of the pilot studies was provided by the IAVI Neutralizing Antibody Consortium and by NIH grants A133292 and A160425 (to D.R.B.). MAbs VRC01, VRCO3, CD4-IgG2, and HJ16 as well as antigens RSC3 and RSC3 Delta 371l were obtained via the NIH AIDS Research and Reference Reagent Program from John Mascola (VRC01 and 03), Progenics Pharmaceuticals (CD4-1gG2), Antonio Lanzavecchia (HJ16), and Zhi-Yong Yang, Peter Kwong, and Gary Nabel (RSC3 and Delta 3711). We thank Peter Kwong and John Mascola (Vaccine Research Center, NIH) for providing additional VRC01, Lisa Cavacini (Beth Israel Deaconess Medical Center) for mAbs B4e8 and F105, and Dietmar and Hermann Katinger (Polymun Scientific GmbH, Austria) for the generous gift of 2G12. We also thank Kate Auyeung for assistance with immunogen preparation, James Kwon, Jose Tam-Huang and Dennis Chau for assistance with cloning, plasmid preparation and protein purification, Savrina Manhas for assistance with neutralization assays and Kevin Henry for critical review of the manuscript during the draft stage. NR 82 TC 14 Z9 14 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 20 PY 2012 VL 30 IS 5 BP 922 EP 930 DI 10.1016/j.vaccine.2011.11.089 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 909IK UT WOS:000301558000016 PM 22142583 ER PT J AU Gonzalez, RG Lev, MH Goldmacher, GV Smith, WS Payabvash, S Harris, GJ Halpern, EF Koroshetz, WJ Camargo, ECS Dillon, WP Furie, KL AF Gonzalez, R. Gilberto Lev, Michael H. Goldmacher, Gregory V. Smith, Wade S. Payabvash, Seyedmehdi Harris, Gordon J. Halpern, Elkan F. Koroshetz, Walter J. Camargo, Erica C. S. Dillon, William P. Furie, Karen L. TI Improved Outcome Prediction Using CT Angiography in Addition to Standard Ischemic Stroke Assessment: Results from the STOPStroke Study SO PLOS ONE LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; COMPUTED-TOMOGRAPHY; DIAGNOSTIC-APPROACH; IMAGING SCALE; SCORE; INFARCTION; MISMATCH; TRIAL; SCANS; RISK AB Purpose: To improve ischemic stroke outcome prediction using imaging information from a prospective cohort who received admission CT angiography (CTA). Methods: In a prospectively designed study, 649 stroke patients diagnosed with acute ischemic stroke had admission NIH stroke scale scores, noncontrast CT (NCCT), CTA, and 6-month outcome assessed using the modified Rankin scale (mRS) scores. Poor outcome was defined as mRS>2. Strokes were classified as "major'' by the (1) Alberta Stroke Program Early CT Score (ASPECTS+) if NCCT ASPECTS was <= 7; (2) Boston Acute Stroke Imaging Scale (BASIS+) if they were ASPECTS+ or CTA showed occlusion of the distal internal carotid, proximal middle cerebral, or basilar arteries; and (3) NIHSS for scores>10. Results: Of 649 patients, 253 (39.0%) had poor outcomes. NIHSS, BASIS, and age, but not ASPECTS, were independent predictors of outcome. BASIS and NIHSS had similar sensitivities, both superior to ASPECTS (p<0.0001). Combining NIHSS with BASIS was highly predictive: 77.6% (114/147) classified as NIHSS>10/BASIS+ had poor outcomes, versus 21.5% (77/358) with NIHSS <= 10/BASIS- (p<0.0001), regardless of treatment. The odds ratios for poor outcome is 12.6 (95% CI: 7.9 to 20.0) in patients who are NIHSS>10/BASIS+ compared to patients who are NIHSS <= 10/BASIS-; the odds ratio is 5.4 (95% CI: 3.5 to 8.5) when compared to patients who are only NIHSS>10 or BASIS+. Conclusions: BASIS and NIHSS are independent outcome predictors. Their combination is stronger than either instrument alone in predicting outcomes. The findings suggest that CTA is a significant clinical tool in routine acute stroke assessment. C1 [Gonzalez, R. Gilberto; Lev, Michael H.; Goldmacher, Gregory V.; Payabvash, Seyedmehdi; Harris, Gordon J.; Halpern, Elkan F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gonzalez, R. Gilberto; Lev, Michael H.; Goldmacher, Gregory V.; Payabvash, Seyedmehdi; Harris, Gordon J.; Halpern, Elkan F.; Camargo, Erica C. S.; Furie, Karen L.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Camargo, Erica C. S.; Furie, Karen L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dillon, William P.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM rggonzalez@partners.org FU National Institute of Health Agency for Health Care Policy and Research (AHCPR) [R01 HS11392-01A1]; GE Healthcare FX This work was supported by the National Institute of Health Agency for Health Care Policy and Research (AHCPR), R01 HS11392-01A1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Michael H. Lev has read the journal's policy and has the following conflicts: He receives research support from GE Healthcare, and is Consultant to Co-Axia, GE Healthcare, and Millennium Pharmaceuticals. Otherwise, the other authors have declared that no competing interests exist. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. NR 28 TC 21 Z9 21 U1 1 U2 3 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 JAN 20 PY 2012 VL 7 IS 1 AR e30352 DI 10.1371/journal.pone.0030352 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 909MH UT WOS:000301568100037 PM 22276182 ER PT J AU Xiong, Y Sheen, J AF Xiong, Yan Sheen, Jen TI Rapamycin and Glucose-Target of Rapamycin (TOR) Protein Signaling in Plants SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MTOR FUNCTION; ARABIDOPSIS; GROWTH; KINASE; EXPRESSION; GENE; TRANSDUCTION; METABOLISM; COMPLEX; INHIBITION AB Target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator that integrates energy, nutrients, growth factors, and stress signals to promote survival and growth in all eukaryotes. The reported land plant resistance to rapamycin and the embryo lethality of the Arabidopsis tor mutants have hindered functional dissection of TOR signaling in plants. We developed sensitive cellular and seedling assays to monitor endogenous Arabidopsis TOR activity based on its conserved S6 kinase (S6K) phosphorylation. Surprisingly, rapamycin effectively inhibits Arabidopsis TOR-S6K1 signaling and retards glucose-mediated root and leaf growth, mimicking estradiol-inducible tor mutants. Rapamycin inhibition is relieved in transgenic plants deficient in Arabidopsis FK506-binding protein 12 (FKP12), whereas FKP12 overexpression dramatically enhances rapamycin sensitivity. The role of Arabidopsis FKP12 is highly specific as overexpression of seven closely related FKP proteins fails to increase rapamycin sensitivity. Rapamycin exerts TOR inhibition by inducing direct interaction between the TOR-FRB (FKP-rapamycin binding) domain and FKP12 in plant cells. We suggest that variable endogenous FKP12 protein levels may underlie the molecular explanation for longstanding enigmatic observations on inconsistent rapamycin resistance in plants and in various mammalian cell lines or diverse animal cell types. Integrative analyses with rapamycin and conditional tor and fkp12 mutants also reveal a central role of glucose-TOR signaling in root hair formation. Our studies demonstrate the power of chemical genetic approaches in the discovery of previously unknown and pivotal functions of glucose-TOR signaling in governing the growth of cotyledons, true leaves, petioles, and primary and secondary roots and root hairs. C1 [Sheen, Jen] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu FU National Institutes of Health [R01 GM60493]; National Science Foundation [IOS-0843244]; Massachusetts General Hospital FX This work was supported, in whole or in part, by National Institutes of Health Grant R01 GM60493 (to J. S.). This work was also supported by National Science Foundation Grant IOS-0843244 (to J. S.).; Supported by the Massachusetts General Hospital Tosteson postdoctoral fellowship. NR 34 TC 55 Z9 63 U1 4 U2 30 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 JAN 20 PY 2012 VL 287 IS 4 BP 2836 EP 2842 DI 10.1074/jbc.M111.300749 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 892NG UT WOS:000300292300055 PM 22134914 ER PT J AU Haeno, H Gonen, M Davis, MB Herman, JM Iacobuzio-Donahue, CA Michor, F AF Haeno, Hiroshi Gonen, Mithat Davis, Meghan B. Herman, Joseph M. Iacobuzio-Donahue, Christine A. Michor, Franziska TI Computational Modeling of Pancreatic Cancer Reveals Kinetics of Metastasis Suggesting Optimum Treatment Strategies SO CELL LA English DT Article ID MATHEMATICAL-MODELS; PROSTATE-CANCER; RAPID AUTOPSY; PROGRESSION; CARCINOMA; SURVIVAL; DORMANCY; CHEMOTHERAPY; INEFFICIENCY; GEMCITABINE AB Pancreatic cancer is a leading cause of cancer-related death, largely due to metastatic dissemination. We investigated pancreatic cancer progression by utilizing a mathematical framework of metastasis formation together with comprehensive data of 228 patients, 101 of whom had autopsies. We found that pancreatic cancer growth is initially exponential. After estimating the rates of pancreatic cancer growth and dissemination, we determined that patients likely harbor metastases at diagnosis and predicted the number and size distribution of metastases as well as patient survival. These findings were validated in an independent database. Finally, we analyzed the effects of different treatment modalities, finding that therapies that efficiently reduce the growth rate of cells earlier in the course of treatment appear to be superior to upfront tumor resection. These predictions can be validated in the clinic. Our interdisciplinary approach provides insights into the dynamics of pancreatic cancer metastasis and identifies optimum therapeutic interventions. C1 [Davis, Meghan B.; Herman, Joseph M.; Iacobuzio-Donahue, Christine A.] Johns Hopkins Univ Hosp, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA. [Iacobuzio-Donahue, Christine A.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21231 USA. [Iacobuzio-Donahue, Christine A.] Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21231 USA. [Iacobuzio-Donahue, Christine A.] Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21231 USA. [Herman, Joseph M.] Johns Hopkins Univ Hosp, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD 21231 USA. [Haeno, Hiroshi; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Haeno, Hiroshi; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Gonen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. RP Iacobuzio-Donahue, CA (reprint author), Johns Hopkins Univ Hosp, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA. EM ciacobu@jhmi.edu; michor@jimmy.harvard.edu RI Gonen, Mithat/E-4826-2012 FU National Institutes of Health [CA106610, CA62924]; Sol Goldman Pancreatic Cancer Research Center; Michael Rolfe Pancreatic Cancer Foundation; George Rubis Endowment for Pancreatic Cancer Research; Joseph C. Monastra Foundation for Pancreatic Cancer Research; Alfredo Scatena Memorial Fund; National Cancer Institute's Physical Sciences-Oncology Center [U54CA143798] FX The authors would like to thank the Michor lab and Georg Lubeck for helpful comments. This work was supported by National Institutes of Health grants CA106610 and CA62924 (C.A.I.-D.), Pilot Funding from the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Foundation, the George Rubis Endowment for Pancreatic Cancer Research, the Joseph C. Monastra Foundation for Pancreatic Cancer Research, and The Alfredo Scatena Memorial Fund. Furthermore, we would like to acknowledge support from the National Cancer Institute's Physical Sciences-Oncology Center, U54CA143798 (H. H., M. G., and F. M.). NR 48 TC 137 Z9 141 U1 2 U2 38 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 20 PY 2012 VL 148 IS 1-2 BP 362 EP 375 DI 10.1016/j.cell.2011.11.060 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 882DC UT WOS:000299540700037 PM 22265421 ER PT J AU Khuman, J Zhang, J Park, J Carroll, JD Donahue, C Whalen, MJ AF Khuman, Jugta Zhang, Jimmy Park, Juyeon Carroll, James D. Donahue, Chad Whalen, Michael J. TI Low-Level Laser Light Therapy Improves Cognitive Deficits and Inhibits Microglial Activation after Controlled Cortical Impact in Mice SO JOURNAL OF NEUROTRAUMA LA English DT Article DE cognition; controlled cortical impact; inflammation; low-level laser light therapy; mice; microglia ID TRAUMATIC BRAIN-INJURY; TERM NEUROLOGICAL DEFICITS; ACUTE ISCHEMIC-STROKE; UNITED-STATES; PROMOTES REGENERATION; FUNCTIONAL RECOVERY; PERIPHERAL-NERVE; EMITTING DIODE; WATER MAZE; TNF-ALPHA AB Low-level laser light therapy (LLLT) exerts beneficial effects on motor and histopathological outcomes after experimental traumatic brain injury (TBI), and coherent near-infrared light has been reported to improve cognitive function in patients with chronic TBI. However, the effects of LLLT on cognitive recovery in experimental TBI are unknown. We hypothesized that LLLT administered after controlled cortical impact (CCI) would improve post-injury Morris water maze (MWM) performance. Low-level laser light (800 nm) was applied directly to the contused parenchyma or transcranially in mice beginning 60-80 min after CCI. Injured mice treated with 60 J/cm(2) (500 mW/cm(2)x2 min) either transcranially or via an open craniotomy had modestly improved latency to the hidden platform (p<0.05 for group), and probe trial performance (p<0.01) compared to non-treated controls. The beneficial effects of LLLT in open craniotomy mice were associated with reduced microgliosis at 48h (21.8 +/- 2.3 versus 39.2 +/- 4.2 IbA-1 + cells/200 x field, p<0.05). Little or no effect of LLLT on post-injury cognitive function was observed using the other doses, a 4-h administration time point and 7-day administration of 60 J/cm(2). No effect of LLLT (60 J/cm(2) open craniotomy) was observed on post-injury motor function (days 1-7), brain edema (24h), nitrosative stress (24h), or lesion volume (14 days). Although further dose optimization and mechanism studies are needed, the data suggest that LLLT might be a therapeutic option to improve cognitive recovery and limit inflammation after TBI. C1 [Khuman, Jugta; Zhang, Jimmy; Park, Juyeon; Whalen, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Sch Med, Charlestown, MA 02129 USA. [Khuman, Jugta; Zhang, Jimmy; Park, Juyeon; Donahue, Chad; Whalen, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Neurosci Ctr, Sch Med, Charlestown, MA 02129 USA. [Carroll, James D.] THOR Photomed Ltd, Chesham, England. RP Whalen, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Sch Med, Charlestown, MA 02129 USA. EM mwhalen@partners.org OI Carroll, James/0000-0002-9205-1061 FU Massachusetts General Hospital Center for the Integration of Medicine and Technology (CIMIT); [RO1NS047447] FX This work was supported by grants from the Massachusetts General Hospital Center for the Integration of Medicine and Technology (CIMIT) (M.J.W.), and RO1NS047447 NR 53 TC 39 Z9 39 U1 3 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JAN 20 PY 2012 VL 29 IS 2 BP 408 EP 417 DI 10.1089/neu.2010.1745 PG 10 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 885SO UT WOS:000299801300020 PM 21851183 ER PT J AU Barnett, BE Ciocca, ML Goenka, R Barnett, LG Wu, JM Laufer, TM Burkhardt, JK Cancro, MP Reiner, SL AF Barnett, Burton E. Ciocca, Maria L. Goenka, Radhika Barnett, Lisa G. Wu, Junmin Laufer, Terri M. Burkhardt, Janis K. Cancro, Michael P. Reiner, Steven L. TI Asymmetric B Cell Division in the Germinal Center Reaction SO SCIENCE LA English DT Article ID T-LYMPHOCYTE DIVISION; BCL-6; ANTIGEN; DIFFERENTIATION; INFLAMMATION; EXPRESSION; RESPONSES AB Lifelong antibody responses to vaccination require reorganization of lymphoid tissue and dynamic intercellular communication called the germinal center reaction. B lymphocytes undergo cellular polarization during antigen stimulation, acquisition, and presentation, which are critical steps for initiating humoral immunity. Here, we show that germinal center B lymphocytes asymmetrically segregate the transcriptional regulator Bcl6, the receptor for interleukin-21, and the ancestral polarity protein atypical protein kinase C to one side of the plane of division, generating unequal inheritance of fate-altering molecules by daughter cells. Germinal center B lymphocytes from mice with a defect in leukocyte adhesion fail to divide asymmetrically. These results suggest that motile cells lacking constitutive attachment can receive provisional polarity cues from the microenvironment to generate daughter cell diversity and self-renewal. C1 [Barnett, Burton E.; Ciocca, Maria L.; Wu, Junmin; Reiner, Steven L.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Goenka, Radhika; Burkhardt, Janis K.; Cancro, Michael P.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Barnett, Burton E.; Ciocca, Maria L.; Barnett, Lisa G.; Wu, Junmin; Laufer, Terri M.; Reiner, Steven L.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Burkhardt, Janis K.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Reiner, SL (reprint author), Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. EM sreiner@columbia.edu FU NIH [AI042370, AI076458, T32GM07229, T32HD007516, 3T32GM007170-36S1, T32AI055428, AI065644]; U.S. Department of Defense [W81WWXWH1010185]; Veterans Administration [BX000435]; Abramson family FX We thank J. Chaix, S. Gordon, M. Paley, and L. Rupp for assistance. We are grateful for funding from the NIH (grants AI042370 and AI076458 to S. L. R., T32GM07229 to B. E. B., T32HD007516 and 3T32GM007170-36S1 to M. L. C., T32AI055428 to R. G., and AI065644 to J.K.B.), the U.S. Department of Defense (grant W81WWXWH1010185 to M. P. C.), Veterans Administration (grant BX000435 to T. M. L.), and the Abramson family (to S. L. R.). The data reported in this paper are tabulated in the main paper and in the supporting online material. The authors declare no conflicts of interest. NR 19 TC 35 Z9 36 U1 0 U2 6 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 JAN 20 PY 2012 VL 335 IS 6066 BP 342 EP 344 DI 10.1126/science.1213495 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 878RE UT WOS:000299273400049 PM 22174128 ER PT J AU Kessler, JD Kahle, KT Sun, TT Meerbrey, KL Schlabach, MR Schmitt, EM Skinner, SO Xu, QK Li, MZ Hartman, ZC Rao, M Yu, P Dominguez-Vidana, R Liang, AC Solimini, NL Bernardi, RJ Yu, B Hsu, T Golding, I Luo, J Osborne, CK Creighton, CJ Hilsenbeck, SG Schiff, R Shaw, CA Elledge, SJ Westbrook, TF AF Kessler, Jessica D. Kahle, Kristopher T. Sun, Tingting Meerbrey, Kristen L. Schlabach, Michael R. Schmitt, Earlene M. Skinner, Samuel O. Xu, Qikai Li, Mamie Z. Hartman, Zachary C. Rao, Mitchell Yu, Peng Dominguez-Vidana, Rocio Liang, Anthony C. Solimini, Nicole L. Bernardi, Ronald J. Yu, Bing Hsu, Tiffany Golding, Ido Luo, Ji Osborne, C. Kent Creighton, Chad J. Hilsenbeck, Susan G. Schiff, Rachel Shaw, Chad A. Elledge, Stephen J. Westbrook, Thomas F. TI A SUMOylation-Dependent Transcriptional Subprogram Is Required for Myc-Driven Tumorigenesis SO SCIENCE LA English DT Article ID NEGATIVE BREAST-CANCER; C-MYC; EXPRESSION SIGNATURE; THERAPY; P53; METASTASIS; TRANSACTIVATION; ACTIVATION; INHIBITION; ADDICTION AB Myc is an oncogenic transcription factor frequently dysregulated in human cancer. To identify pathways supporting the Myc oncogenic program, we used a genome-wide RNA interference screen to search for Myc-synthetic lethal genes and uncovered a role for the SUMO-activating enzyme (SAE1/2). Loss of SAE1/2 enzymatic activity drives synthetic lethality with Myc. Inactivation of SAE2 leads to mitotic catastrophe and cell death upon Myc hyperactivation. Mechanistically, SAE2 inhibition switches a transcriptional subprogram of Myc from activated to repressed. A subset of these SUMOylation-dependent Myc switchers (SMS genes) is required for mitotic spindle function and to support the Myc oncogenic program. SAE2 is required for growth of Myc-dependent tumors in mice, and gene expression analyses of Myc-high human breast cancers suggest that low SAE1 and SAE2 abundance in the tumors correlates with longer metastasis-free survival of the patients. Thus, inhibition of SUMOylation may merit investigation as a possible therapy for Myc-driven human cancers. C1 [Kahle, Kristopher T.; Schlabach, Michael R.; Xu, Qikai; Li, Mamie Z.; Liang, Anthony C.; Solimini, Nicole L.; Elledge, Stephen J.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Brigham & Womens Hosp,Div Genet,Dept Genet, Boston, MA 02115 USA. [Kessler, Jessica D.; Sun, Tingting; Meerbrey, Kristen L.; Schmitt, Earlene M.; Skinner, Samuel O.; Dominguez-Vidana, Rocio; Hsu, Tiffany; Golding, Ido; Westbrook, Thomas F.] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA. [Kessler, Jessica D.; Meerbrey, Kristen L.; Schmitt, Earlene M.; Rao, Mitchell; Yu, Peng; Dominguez-Vidana, Rocio; Hsu, Tiffany; Shaw, Chad A.; Westbrook, Thomas F.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Skinner, Samuel O.; Golding, Ido] Univ Illinois, Dept Phys, Urbana, IL 61801 USA. [Hartman, Zachary C.] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. [Bernardi, Ronald J.; Westbrook, Thomas F.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Yu, Bing; Luo, Ji] NCI, Med Oncol Branch, Ctr Drive, Bethesda, MD 20892 USA. [Osborne, C. Kent; Creighton, Chad J.; Hilsenbeck, Susan G.; Schiff, Rachel; Westbrook, Thomas F.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Osborne, C. Kent; Hilsenbeck, Susan G.; Schiff, Rachel] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Osborne, C. Kent; Schiff, Rachel] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Osborne, C. Kent; Schiff, Rachel] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Creighton, Chad J.; Hilsenbeck, Susan G.] Baylor Coll Med, Div Biostat, Houston, TX 77030 USA. RP Elledge, SJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Brigham & Womens Hosp,Div Genet,Dept Genet, Boston, MA 02115 USA. EM selledge@genetics.med.harvard.edu; thomasw@bcm.edu RI Dominguez-Vidana, Rocio/A-1153-2009; OI Dominguez-Vidana, Rocio/0000-0003-3855-5178; Shaw, Chad/0000-0001-7267-5398 FU NIH [T32HD05520/T32CA090221-09, R01GM082837, CA149196]; U.S. Department of Defense [W81XWH-10-1-0354]; Human Frontier Science Program [RGY70/2008]; Welch Foundation [Q-1759]; NSF [082265]; Susan G. Komen for the Cure [KG090355]; CPRIT [RP120583]; Specialized Program of Research Excellence developmental grant [P50 CA058183]; SU2C-American Association for Cancer Research; U.S. Army [W81XWH0410197] FX We thank C. Bland for critical comments on the manuscript and T. Mitchell, W. Choi, S. Songyang, and the BCM C-BASS and CCSC Cores for reagents and technical assistance. J.D.K and K. L. M. are supported by NIH training grants T32HD05520/T32CA090221-09 and U.S. Department of Defense predoctoral fellowship W81XWH-10-1-0354, respectively. The Golding lab is supported by NIH grant R01GM082837, Human Frontier Science Program grant RGY70/2008, Welch Foundation grant Q-1759, and NSF grant 082265 (PFC: Center for the Physics of Living Cells). This work was supported by a Susan G. Komen for the Cure grant (KG090355), CPRIT grant (RP120583), and NIH grant (CA149196) to T. F. W., Specialized Program of Research Excellence developmental grant (P50 CA058183) to T. F. W., SU2C-American Association for Cancer Research Breast Cancer program grant to R. S. and C.K.O., and U.S. Army Innovator Award (W81XWH0410197) to S.J.E. S.J.E. is an Investigator with the Howard Hughes Medical Institute. T. F. W. is a scholar of The V Foundation and The Mary Kay Ash Foundation for Cancer Research. Gene Expression data are deposited in GEO (accession no. GSE34055). NR 39 TC 143 Z9 146 U1 3 U2 23 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 JAN 20 PY 2012 VL 335 IS 6066 BP 348 EP 353 DI 10.1126/science.1212728 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 878RE UT WOS:000299273400051 PM 22157079 ER PT J AU Lane, SW De Vita, S Alexander, KA Karaman, R Milsom, MD Dorrance, AM Purdon, A Louis, L Bouxsein, ML Williams, DA AF Lane, Steven W. De Vita, Serena Alexander, Kylie A. Karaman, Ruchan Milsom, Michael D. Dorrance, Adrienne M. Purdon, Amy Louis, Leeann Bouxsein, Mary L. Williams, David A. TI Rac signaling in osteoblastic cells is required for normal bone development but is dispensable for hematopoietic development SO BLOOD LA English DT Article ID STEM-CELLS; PROGENITOR CELLS; N-CADHERIN; GUANOSINE TRIPHOSPHATASES; MARROW MICROENVIRONMENT; ENDOSTEAL NICHE; BETA-CATENIN; ADHESION; MAINTENANCE; ENGRAFTMENT AB Hematopoietic stem cells (HSCs) interact with osteoblastic, stromal, and vascular components of the BM hematopoietic microenvironment (HM) that are required for the maintenance of long-term self-renewal in vivo. Osteoblasts have been reported to be a critical cell type making up the HSC niche in vivo. Rac1 GTPase has been implicated in adhesion, spreading, and differentiation of osteoblast cell lines and is critical for HSC engraftment and retention. Recent data suggest a differential role of GTPases in endosteal/osteoblastic versus perivascular niche function. However, whether Rac signaling pathways are also necessary in the cell-extrinsic control of HSC function within the HM has not been examined. In the present study, genetic and inducible models of Rac deletion were used to demonstrate that Rac depletion causes impaired proliferation and induction of apoptosis in the OP9 cell line and in primary BM stromal cells. Deletion of Rac proteins caused reduced trabecular and cortical long bone growth in vivo. Surprisingly, HSC function and maintenance of hematopoiesis in vivo was preserved despite these substantial cell-extrinsic changes. These data have implications for therapeutic strategies to target Rac signaling in HSC mobilization and in the treatment of leukemia and provide clarification to our evolving concepts of HSC-HM interactions. (Blood. 2012;119(3):736-744) C1 [Lane, Steven W.; De Vita, Serena; Karaman, Ruchan; Milsom, Michael D.; Dorrance, Adrienne M.; Williams, David A.] Harvard Univ, Div Hematol Oncol, Childrens Hosp Boston, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [Lane, Steven W.; De Vita, Serena; Karaman, Ruchan; Milsom, Michael D.; Dorrance, Adrienne M.; Williams, David A.] Harvard Stem Cell Inst, Boston, MA USA. [Lane, Steven W.; Alexander, Kylie A.; Purdon, Amy] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Louis, Leeann; Bouxsein, Mary L.] Harvard Univ, Ctr Adv Orthoped Studies, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02115 USA. RP Williams, DA (reprint author), Harvard Univ, Div Hematol Oncol, Childrens Hosp Boston, Dana Farber Canc Inst,Med Sch, 300 Long Wood Ave,Karp 08125-3, Boston, MA 02115 USA. EM dawilliams@childrens.harvard.edu RI Lane, Steven/C-3215-2012; Alexander, Kylie /P-2666-2016 OI Lane, Steven/0000-0002-8050-6209; Alexander, Kylie /0000-0001-5772-0277 FU National Health and Medical Research Council of Australia; US National Institutes of Health [DK62757] FX S.W.L. has received funding support from the National Health and Medical Research Council of Australia. D.A.W. has received funding support from the US National Institutes of Health (grant DK62757). NR 46 TC 10 Z9 10 U1 0 U2 3 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 JAN 19 PY 2012 VL 119 IS 3 BP 736 EP 744 DI 10.1182/blood-2011-07-368753 PG 9 WC Hematology SC Hematology GA 882WH UT WOS:000299594100014 PM 22123845 ER PT J AU Yin, L Kosugi, M Kufe, D AF Yin, Li Kosugi, Michio Kufe, Donald TI Inhibition of the MUC1-C oncoprotein induces multiple myeloma cell death by down-regulating TIGAR expression and depleting NADPH SO BLOOD LA English DT Article ID REACTIVE OXYGEN; SURVIVAL RESPONSE; OXIDATIVE STRESS; INDUCED ACTIVATION; INDUCED APOPTOSIS; LEUKEMIA-CELLS; CANCER CELLS; INDUCTION; PROTEIN; GROWTH AB The MUC1-C oncoprotein is aberrantly expressed in most multiple myeloma cells. However, the functional significance of MUC1-C expression in multiple myeloma is not known. The present studies demonstrate that treatment of multiple myeloma cells with a MUC1-C inhibitor is associated with increases in reactive oxygen species (ROS), oxidation of mitochondrial cardiolipin, and loss of the mitochondrial transmembrane potential. The MUC1-C inhibitor-induced increases in ROS were also associated with downregulation of the p53-inducible regulator of glycolysis and apoptosis (TIGAR). In concert with the decrease in TIGAR expression, which regulates the pentose phosphate pathway, treatment with the MUC1-C inhibitor reduced production of NADPH, and in turn glutathione (GSH) levels. TIGAR protects against oxidative stress-induced apoptosis. The suppression of TIGAR and NADPH levels thus contributed to ROS-mediated late apoptosis/necrosis of multiple myeloma cells. These findings indicate that multiple myeloma cells are dependent on MUC1-C and TIGAR for maintenance of redox balance and that targeting MUC1-C activates a cascade involving TIGAR suppression that contributes to multiple myeloma cell death. (Blood. 2012;119(3):810-816) C1 [Yin, Li; Kosugi, Michio; Kufe, Donald] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 450 Brookline Ave, Boston, MA 02115 USA. EM bdonald_kufe@dfci.harvard.edu FU Leukemia & Lymphoma Society; Multiple Myeloma Research Foundation; National Cancer Institute [CA42802] FX This study was supported by the Leukemia & Lymphoma Society, the Multiple Myeloma Research Foundation, and the National Cancer Institute grant CA42802. NR 38 TC 34 Z9 36 U1 2 U2 7 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 JAN 19 PY 2012 VL 119 IS 3 BP 810 EP 816 DI 10.1182/blood-2011-07-369686 PG 7 WC Hematology SC Hematology GA 882WH UT WOS:000299594100022 PM 22117045 ER PT J AU Jackevicius, CA Chou, MM Ross, JS Shah, ND Krumholz, HM AF Jackevicius, Cynthia A. Chou, Mindy M. Ross, Joseph S. Shah, Nilay D. Krumholz, Harlan M. TI Generic Atorvastatin and Health Care Costs SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Pomona, CA 91766 USA. [Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Toronto, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Chou, Mindy M.] Indian Hlth Serv, San Fidel, NM USA. [Ross, Joseph S.; Krumholz, Harlan M.] Yale Univ, Sch Med, New Haven, CT USA. [Ross, Joseph S.; Krumholz, Harlan M.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Shah, Nilay D.] Mayo Clin, Rochester, MN USA. RP Jackevicius, CA (reprint author), Western Univ Hlth Sci, Pomona, CA 91766 USA. FU NHLBI NIH HHS [U01 HL105270]; NIA NIH HHS [K08 AG032886, K08 AG032886-04] NR 5 TC 34 Z9 35 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 JAN 19 PY 2012 VL 366 IS 3 BP 201 EP 204 DI 10.1056/NEJMp1113112 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 877RZ UT WOS:000299201400004 PM 22149736 ER PT J AU Su, F Viros, A Milagre, C Trunzer, K Bollag, G Spleiss, O Reis, JS Kong, XJ Koya, RC Flaherty, KT Chapman, PB Kim, MJ Hayward, R Martin, M Yang, H Wang, QQ Hilton, H Hang, JS Noe, J Lambros, M Geyer, F Dhomen, N Niculescu-Duvaz, I Zambon, A Niculescu-Duvaz, D Preece, N Robert, L Otte, NJ Mok, S Kee, D Ma, Y Zhang, C Habets, G Burton, EA Wong, B Nguyen, H Kockx, M Andries, L Lestini, B Nolop, KB Lee, RJ Joe, AK Troy, JL Gonzalez, R Hutson, TE Puzanov, I Chmielowski, B Springer, CJ McArthur, GA Sosman, JA Lo, RS Ribas, A Marais, R AF Su, Fei Viros, Amaya Milagre, Carla Trunzer, Kerstin Bollag, Gideon Spleiss, Olivia Reis-Filho, Jorge S. Kong, Xiangju Koya, Richard C. Flaherty, Keith T. Chapman, Paul B. Kim, Min Jung Hayward, Robert Martin, Matthew Yang, Hong Wang, Qiongqing Hilton, Holly Hang, Julie S. Noe, Johannes Lambros, Maryou Geyer, Felipe Dhomen, Nathalie Niculescu-Duvaz, Ion Zambon, Alfonso Niculescu-Duvaz, Dan Preece, Natasha Robert, Lidia Otte, Nicholas J. Mok, Stephen Kee, Damien Ma, Yan Zhang, Chao Habets, Gaston Burton, Elizabeth A. Wong, Bernice Hoa Nguyen Kockx, Mark Andries, Luc Lestini, Brian Nolop, Keith B. Lee, Richard J. Joe, Andrew K. Troy, James L. Gonzalez, Rene Hutson, Thomas E. Puzanov, Igor Chmielowski, Bartosz Springer, Caroline J. McArthur, Grant A. Sosman, Jeffrey A. Lo, Roger S. Ribas, Antoni Marais, Richard TI RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID B-RAF; MELANOMA; ACTIVATION; CARCINOGENESIS; PLX4032; KINASE; PROLIFERATION; VEMURAFENIB; RESISTANCE; THERAPY AB BACKGROUND Cutaneous squamous-cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors. METHODS We performed a molecular analysis to identify oncogenic mutations (HRAS, KRAS, NRAS, CDKN2A, and TP53) in the lesions from patients treated with the BRAF inhibitor vemurafenib. An analysis of an independent validation set and functional studies with BRAF inhibitors in the presence of the prevalent RAS mutation was also performed. RESULTS Among 21 tumor samples, 13 had RAS mutations (12 in HRAS). In a validation set of 14 samples, 8 had RAS mutations (4 in HRAS). Thus, 60% (21 of 35) of the specimens harbored RAS mutations, the most prevalent being HRAS Q61L. Increased proliferation of HRAS Q61L-mutant cell lines exposed to vemurafenib was associated with mitogen-activated protein kinase (MAPK)-pathway signaling and activation of ERK-mediated transcription. In a mouse model of HRAS Q61L-mediated skin carcinogenesis, the vemurafenib analogue PLX4720 was not an initiator or a promoter of carcinogenesis but accelerated growth of the lesions harboring HRAS mutations, and this growth was blocked by concomitant treatment with a MEK inhibitor. CONCLUSIONS Mutations in RAS, particularly HRAS, are frequent in cutaneous squamous-cell carcinomas and keratoacanthomas that develop in patients treated with vemurafenib. The molecular mechanism is consistent with the paradoxical activation of MAPK signaling and leads to accelerated growth of these lesions. (Funded by Hoffmann-La Roche and others; ClinicalTrials.gov numbers, NCT00405587, NCT00949702, NCT01001299, and NCT01006980.) C1 [Ribas, Antoni] Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Med Ctr, Los Angeles, CA 90095 USA. [Su, Fei; Kim, Min Jung; Yang, Hong; Wang, Qiongqing; Hilton, Holly; Hang, Julie S.; Lestini, Brian; Lee, Richard J.; Joe, Andrew K.] Hoffmann La Roche, Nutley, NJ USA. [Viros, Amaya; Milagre, Carla; Reis-Filho, Jorge S.; Hayward, Robert; Martin, Matthew; Lambros, Maryou; Geyer, Felipe; Dhomen, Nathalie; Niculescu-Duvaz, Ion; Zambon, Alfonso; Niculescu-Duvaz, Dan; Preece, Natasha; Springer, Caroline J.; Marais, Richard] Inst Canc Res, London SW3 6JB, England. [Viros, Amaya] Univ Autonoma Barcelona, Hosp Vall dHebron, E-08193 Barcelona, Spain. [Trunzer, Kerstin; Spleiss, Olivia; Noe, Johannes] Hoffmann La Roche AG, Basel, Switzerland. [Bollag, Gideon; Ma, Yan; Zhang, Chao; Habets, Gaston; Burton, Elizabeth A.; Wong, Bernice; Hoa Nguyen; Nolop, Keith B.] Plexxikon, Berkeley, CA USA. [Kong, Xiangju; Koya, Richard C.; Robert, Lidia; Otte, Nicholas J.; Mok, Stephen; Chmielowski, Bartosz; Lo, Roger S.; Ribas, Antoni] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Flaherty, Keith T.] Harvard Univ, Sch Med, Boston, MA USA. [Chapman, Paul B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kee, Damien; McArthur, Grant A.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Kockx, Mark; Andries, Luc] HistoGeneX, Antwerp, Belgium. [Troy, James L.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gonzalez, Rene] Univ Colorado, Ctr Canc, Aurora, CO USA. [Hutson, Thomas E.] Texas Oncol Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [Puzanov, Igor; Sosman, Jeffrey A.] Vanderbilt Univ, Nashville, TN USA. RP Ribas, A (reprint author), Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Med Ctr, 11-934 Factor Bldg,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM aribas@mednet.ucla.edu; richard.marais@icr.ac.uk RI Zambon, Alfonso/J-2529-2012 OI Zambon, Alfonso/0000-0002-8074-2308 FU Hoffmann-La Roche; Plexxikon; Seaver Institute; Louise Belley and Richard Schnarr Fund; Fred L. Hartley Family Foundation; Wesley Coyle Memorial Fund; Ruby Family Foundation; Albert Stroberg and Betsy Patterson Fund; Jonsson Cancer Center Foundation; Caltech-UCLA Joint Center for Translational Medicine; European Organisation for Research and Treatment of Cancer Melanoma Group, Cancer Research U.K. (CRUK) [C107/A10433, CRUK-A8274]; American Institute for Cancer Research [09-0773]; Institute of Cancer Research; Breakthrough Breast Cancer FX Supported in part by Hoffmann-La Roche and Plexxikon (to Drs. Su, Trunzer, and Bollag); the Seaver Institute, the Louise Belley and Richard Schnarr Fund, the Fred L. Hartley Family Foundation, the Wesley Coyle Memorial Fund, the Ruby Family Foundation, the Albert Stroberg and Betsy Patterson Fund, the Jonsson Cancer Center Foundation, and the Caltech-UCLA Joint Center for Translational Medicine (to Drs. Lo and Ribas); the European Organisation for Research and Treatment of Cancer Melanoma Group, Cancer Research U.K. (CRUK) (C107/A10433 and CRUK-A8274), the American Institute for Cancer Research (09-0773), and the Institute of Cancer Research (to Dr. Marais); and Breakthrough Breast Cancer and the 2010 CRUK Future Leaders Prize in Cancer Research (to Dr. Reis-Filho). NR 34 TC 493 Z9 498 U1 4 U2 47 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 19 PY 2012 VL 366 IS 3 BP 207 EP 215 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 877RZ UT WOS:000299201400006 PM 22256804 ER PT J AU Heravi-Moussavi, A Anglesio, MS Cheng, SWG Senz, J Yang, W Prentice, L Fejes, AP Chow, C Tone, A Kalloger, SE Hamel, N Roth, A Ha, G Wan, ANC Maines-Bandiera, S Salamanca, C Pasini, B Clarke, BA Lee, AF Lee, CH Zhao, CQ Young, RH Aparicio, SA Sorensen, PHB Woo, MMM Boyd, N Jones, SJM Hirst, M Marra, MA Gilks, B Shah, SP Foulkes, WD Morin, GB Huntsman, DG AF Heravi-Moussavi, Alireza Anglesio, Michael S. Cheng, S. -W. Grace Senz, Janine Yang, Winnie Prentice, Leah Fejes, Anthony P. Chow, Christine Tone, Alicia Kalloger, Steve E. Hamel, Nancy Roth, Andrew Ha, Gavin Wan, Adrian N. C. Maines-Bandiera, Sarah Salamanca, Clara Pasini, Barbara Clarke, Blaise A. Lee, Anna F. Lee, Cheng-Han Zhao, Chengquan Young, Robert H. Aparicio, Samuel A. Sorensen, Poul H. B. Woo, Michelle M. M. Boyd, Niki Jones, Steven J. M. Hirst, Martin Marra, Marco A. Gilks, Blake Shah, Sohrab P. Foulkes, William D. Morin, Gregg B. Huntsman, David G. TI Recurrent Somatic DICER1 Mutations in Nonepithelial Ovarian Cancers SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GRANULOSA-CELL TUMORS; RNASE-III; EXPRESSION; MICRORNAS; PROGNOSIS; SELECTION; DROSHA; FOXL2 AB BACKGROUND Germline truncating mutations in DICER1, an endoribonuclease in the RNase III family that is essential for processing microRNAs, have been observed in families with the pleuropulmonary blastoma-family tumor and dysplasia syndrome. Mutation carriers are at risk for nonepithelial ovarian tumors, notably sex cord-stromal tumors. METHODS We sequenced the whole transcriptomes or exomes of 14 nonepithelial ovarian tumors and noted closely clustered mutations in the region of DICER1 encoding the RNase IIIb domain of DICER1 in four samples. We then sequenced this region of DICER1 in additional ovarian tumors and in certain other tumors and queried the effect of the mutations on the enzymatic activity of DICER1 using in vitro RNA cleavage assays. RESULTS DICER1 mutations in the RNase IIIb domain were found in 30 of 102 nonepithelial ovarian tumors (29%), predominantly in Sertoli-Leydig cell tumors (26 of 43, or 60%), including 4 tumors with additional germline DICER1 mutations. These mutations were restricted to codons encoding metal-binding sites within the RNase IIIb catalytic centers, which are critical for microRNA interaction and cleavage, and were somatic in all 16 samples in which germline DNA was available for testing. We also detected mutations in 1 of 14 nonseminomatous testicular germ-cell tumors, in 2 of 5 embryonal rhabdomyosarcomas, and in 1 of 266 epithelial ovarian and endometrial carcinomas. The mutant DICER1 proteins had reduced RNase IIIb activity but retained RNase IIIa activity. CONCLUSIONS Somatic missense mutations affecting the RNase IIIb domain of DICER1 are common in nonepithelial ovarian tumors. These mutations do not obliterate DICER1 function but alter it in specific cell types, a novel mechanism through which perturbation of microRNA processing may be oncogenic. (Funded by the Terry Fox Research Institute and others.) C1 [Huntsman, David G.] Univ British Columbia, British Columbia Canc Agcy, Ovarian Canc Res Program, Vancouver, BC V5Z 4E6, Canada. [Heravi-Moussavi, Alireza; Cheng, S. -W. Grace; Roth, Andrew; Ha, Gavin; Wan, Adrian N. C.; Maines-Bandiera, Sarah; Salamanca, Clara; Aparicio, Samuel A.; Sorensen, Poul H. B.; Jones, Steven J. M.; Marra, Marco A.; Shah, Sohrab P.; Morin, Gregg B.; Huntsman, David G.] Univ British Columbia, British Columbia Canc Res Ctr, Vancouver, BC V5Z 1M9, Canada. [Chow, Christine; Kalloger, Steve E.; Gilks, Blake; Huntsman, David G.] Univ British Columbia, Vancouver Gen Hosp, Genet Pathol Evaluat Ctr, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. [Huntsman, David G.] Univ British Columbia, Ctr Translat & Appl Genom, British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Jones, Steven J. M.; Marra, Marco A.; Morin, Gregg B.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Anglesio, Michael S.; Lee, Anna F.; Lee, Cheng-Han; Aparicio, Samuel A.; Sorensen, Poul H. B.; Gilks, Blake; Shah, Sohrab P.; Huntsman, David G.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Hamel, Nancy; Foulkes, William D.] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ, Canada. [Hamel, Nancy; Foulkes, William D.] McGill Univ, Dept Human Genet, Program Canc Genet, Montreal, PQ, Canada. [Cheng, S. -W. Grace; Fejes, Anthony P.; Jones, Steven J. M.; Hirst, Martin; Marra, Marco A.; Morin, Gregg B.] Univ British Columbia, British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada. [Hamel, Nancy; Foulkes, William D.] McGill Univ, Res Inst, Ctr Hlth, Montreal, PQ, Canada. [Foulkes, William D.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Segal Canc Ctr, Montreal, PQ H3T 1E2, Canada. [Pasini, Barbara] Univ Turin, Dept Genet, Turin, Italy. [Pasini, Barbara] Univ Turin, Dept Biol, Turin, Italy. [Pasini, Barbara] Univ Turin, Dept Biochem, Turin, Italy. [Clarke, Blaise A.] Univ Toronto, Fac Med, Dept Lab Med, Toronto, ON, Canada. [Clarke, Blaise A.] Univ Toronto, Dept Pathobiol, Fac Med, Toronto, ON, Canada. [Zhao, Chengquan] Univ Pittsburgh, Magee Womens Hosp, Dept Pathol, Med Ctr, Pittsburgh, PA 15213 USA. [Young, Robert H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Young, Robert H.] Harvard Univ, Sch Med, Boston, MA USA. RP Huntsman, DG (reprint author), Univ British Columbia, British Columbia Canc Agcy, Ovarian Canc Res Program, Rm 3427,600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. EM gmorin@bcgsc.ca; dhuntsma@bccancer.bc.ca RI Morin, Gregg/E-9123-2012; Tang, Macy/B-9798-2014; Hirst, Martin/B-7684-2016; Jones, Steven/C-3621-2009; Marra, Marco/B-5987-2008; OI Morin, Gregg/0000-0001-8949-4374; Anglesio, Michael/0000-0003-1639-5003; Lee, Anna/0000-0002-6703-0656; foulkes, william/0000-0001-7427-4651 FU Terry Fox Research Institute; British Columbia Cancer Foundation; Vancouver General Hospital-University of British Columbia Hospital Foundation; Canadian Institutes of Health Research; Genome Canada; Michael Smith Foundation for Health Research; Marsha Rivkin Centre for Ovarian Cancer Research; Susan G. Komen for the Cure; Weekend to End Women's Cancer; Ovarian Cancer Research Program of British Columbia (OvCaRe), Ovarian Cancer Canada; National Cancer Institute through the Cooperative Human Tissue Network; Gynecologic Oncology Group FX Supported by grants from the Terry Fox Research Institute, the British Columbia Cancer Foundation, the Vancouver General Hospital-University of British Columbia Hospital Foundation, the Canadian Institutes of Health Research, Genome Canada, the Michael Smith Foundation for Health Research, the Marsha Rivkin Centre for Ovarian Cancer Research, Susan G. Komen for the Cure, and the Weekend to End Women's Cancer. The contributing tumor banks were supported by the Ovarian Cancer Research Program of British Columbia (OvCaRe), Ovarian Cancer Canada, and the National Cancer Institute through the Cooperative Human Tissue Network and the Gynecologic Oncology Group. NR 40 TC 146 Z9 155 U1 1 U2 19 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 JAN 19 PY 2012 VL 366 IS 3 BP 234 EP 242 DI 10.1056/NEJMoa1102903 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 877RZ UT WOS:000299201400009 PM 22187960 ER PT J AU Kotton, DN Muse, VV Nishino, M AF Kotton, Darrell N. Muse, Victorine V. Nishino, Michiya TI Case 2-2012: A 63-Year-Old Woman with Dyspnea and Rapidly Progressive Respiratory Failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID KASABACH-MERRITT-SYNDROME; BREAST IMPLANTS; HALO SIGN; METASTATIC ANGIOSARCOMA; ASPERGILLOSIS; DIAGNOSIS; SILICONE; GALACTOMANNAN; DISEASES; CT C1 [Kotton, Darrell N.] Boston Med Ctr, Dept Med, Boston, MA 02218 USA. [Kotton, Darrell N.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Muse, Victorine V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Nishino, Michiya] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Muse, Victorine V.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Nishino, Michiya] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kotton, DN (reprint author), Boston Med Ctr, Dept Med, Boston, MA 02218 USA. NR 32 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 19 PY 2012 VL 366 IS 3 BP 259 EP 269 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 877RZ UT WOS:000299201400013 PM 22256809 ER PT J AU Chung, RT AF Chung, Raymond T. TI A Watershed Moment in the Treatment of Hepatitis C SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SUSTAINED VIROLOGICAL RESPONSE; GENOTYPE 1 INFECTION; PEGINTERFERON ALPHA-2A; VIRUS-INFECTION; PLUS RIBAVIRIN; BOCEPREVIR; TELAPREVIR C1 [Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. [Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. NR 10 TC 32 Z9 33 U1 0 U2 4 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 JAN 19 PY 2012 VL 366 IS 3 BP 273 EP 275 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 877RZ UT WOS:000299201400015 PM 22256811 ER PT J AU Robinton, DA Daley, GQ AF Robinton, Daisy A. Daley, George Q. TI The promise of induced pluripotent stem cells in research and therapy SO NATURE LA English DT Review ID HUMAN SOMATIC-CELLS; HUMAN IPS CELLS; DYSKERATOSIS-CONGENITA; HUMAN FIBROBLASTS; CHROMOSOMAL-ABERRATIONS; REPROGRAMMING FACTORS; PARKINSONS-DISEASE; EPIGENETIC MEMORY; GENE-EXPRESSION; DEFINED FACTORS AB The field of stem-cell biology has been catapulted forward by the startling development of reprogramming technology. The ability to restore pluripotency to somatic cells through the ectopic co-expression of reprogramming factors has created powerful new opportunities for modelling human diseases and offers hope for personalized regenerative cell therapies. While the field is racing ahead, some researchers are pausing to evaluate whether induced pluripotent stem cells are indeed the true equivalents of embryonic stem cells and whether subtle differences between these types of cell might affect their research applications and therapeutic potential. C1 [Robinton, Daisy A.; Daley, George Q.] Childrens Hosp Boston, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA. [Robinton, Daisy A.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Robinton, Daisy A.; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Robinton, Daisy A.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Robinton, Daisy A.; Daley, George Q.] Broad Inst, Cambridge, MA 02142 USA. [Robinton, Daisy A.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Daley, GQ (reprint author), Childrens Hosp Boston, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU National Institutes of Health [RO1-DK70055, RO1-DK59279, UO1-HL100001]; American Recovery and Reinvestment Act [RC2-HL102815]; Roche Foundation for Anemia Research; Alex's Lemonade Stand Foundation; Harvard Stem Cell Institute; Burroughs Wellcome Fund; Leukemia and Lymphoma Society FX G.Q.D. is supported by grants from the National Institutes of Health (RO1-DK70055, RO1-DK59279 and UO1-HL100001, as well as special funds from the American Recovery and Reinvestment Act of 2009 (RC2-HL102815), the Roche Foundation for Anemia Research, Alex's Lemonade Stand Foundation and the Harvard Stem Cell Institute. G. Q. D. is an affiliate member of the Broad Institute, a recipient of Clinical Scientist Awards in Translational Research from the Burroughs Wellcome Fund and the Leukemia and Lymphoma Society, and an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. We gratefully acknowledge A. de Los Angeles for providing the images for Fig. 1a, d, f; T. Onder, for Fig. 1b; and A. Cherry, for Fig. 1c, e. NR 100 TC 439 Z9 457 U1 50 U2 429 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 19 PY 2012 VL 481 IS 7381 BP 295 EP 305 DI 10.1038/nature10761 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 877VK UT WOS:000299210600031 PM 22258608 ER PT J AU Zhang, JH Benavente, CA McEvoy, J Flores-Otero, J Ding, L Chen, X Ulyanov, A Wu, G Wilson, M Wang, JM Brennan, R Rusch, M Manning, AL Ma, J Easton, J Shurtleff, S Mullighan, C Pounds, S Mukatira, S Gupta, P Neale, G Zhao, D Lu, C Fulton, RS Fulton, LL Hong, X Dooling, DJ Ochoa, K Naeve, C Dyson, NJ Mardis, ER Bahrami, A Ellison, D Wilson, RK Downing, JR Dyer, MA AF Zhang, Jinghui Benavente, Claudia A. McEvoy, Justina Flores-Otero, Jacqueline Ding, Li Chen, Xiang Ulyanov, Anatoly Wu, Gang Wilson, Matthew Wang, Jianmin Brennan, Rachel Rusch, Michael Manning, Amity L. Ma, Jing Easton, John Shurtleff, Sheila Mullighan, Charles Pounds, Stanley Mukatira, Suraj Gupta, Pankaj Neale, Geoff Zhao, David Lu, Charles Fulton, Robert S. Fulton, Lucinda L. Hong, Xin Dooling, David J. Ochoa, Kerri Naeve, Clayton Dyson, Nicholas J. Mardis, Elaine R. Bahrami, Armita Ellison, David Wilson, Richard K. Downing, James R. Dyer, Michael A. TI A novel retinoblastoma therapy from genomic and epigenetic analyses SO NATURE LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TYROSINE KINASE; CANCER EPIGENETICS; CHROMOSOMAL INSTABILITY; SYK INHIBITOR; B-CELLS; TARGET; EXPRESSION; ANEUPLOIDY; LYMPHOMA AB Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss. C1 [Benavente, Claudia A.; McEvoy, Justina; Flores-Otero, Jacqueline; Brennan, Rachel; Dyer, Michael A.] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. [Zhang, Jinghui; Chen, Xiang; Ulyanov, Anatoly; Wu, Gang; Rusch, Michael; Easton, John] St Jude Childrens Hosp, Dept Computat Biol & Bioinformat, Memphis, TN 38105 USA. [Ding, Li; Lu, Charles; Fulton, Robert S.; Fulton, Lucinda L.; Hong, Xin; Dooling, David J.; Ochoa, Kerri; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Sch Med St Louis, Genome Inst, St Louis, MO 63108 USA. [Ding, Li; Fulton, Robert S.; Fulton, Lucinda L.; Hong, Xin; Dooling, David J.; Ochoa, Kerri; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Sch Med St Louis, Dept Genet, St Louis, MO 63108 USA. [Wilson, Matthew; Dyer, Michael A.] Univ Tennessee, Hlth Sci Ctr, Dept Ophthalmol, Memphis, TN 38163 USA. [Wilson, Matthew] St Jude Childrens Hosp, Dept Surg, Memphis, TN 38105 USA. [Wang, Jianmin; Mukatira, Suraj; Gupta, Pankaj; Neale, Geoff] St Jude Childrens Hosp, Hartwell Ctr Biotechnol & Bioinformat, Memphis, TN 38105 USA. [Manning, Amity L.; Dyson, Nicholas J.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Ma, Jing; Shurtleff, Sheila; Mullighan, Charles; Bahrami, Armita; Ellison, David; Downing, James R.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. [Pounds, Stanley] St Jude Childrens Hosp, Dept Biostat, Memphis, TN 38105 USA. [Zhao, David; Naeve, Clayton] St Jude Childrens Hosp, Dept Informat Sci, Memphis, TN 38105 USA. [Mardis, Elaine R.] Washington Univ, Sch Med St Louis, Siteman Canc Ctr, St Louis, MO 63108 USA. [Wilson, Richard K.] Washington Univ, Sch Med St Louis, Dept Med, St Louis, MO 63108 USA. [Dyer, Michael A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Dyer, MA (reprint author), St Jude Childrens Hosp, Dept Dev Neurobiol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM rwilson@wustl.edu; james.downing@stjude.org; michael.dyer@stjude.org OI Pounds, Stanley/0000-0002-9167-2114; Mullighan, Charles/0000-0002-1871-1850; McEvoy, Justina/0000-0003-0382-1288 FU St Jude Children's Research Hospital - Washington University; St Jude Children's Research Hospital; NCI [CA21765]; NIH [EY014867, EY018599, GM81607, CA64402]; American Cancer Society; Research to Prevent Blindness Foundation; American Lebanese Syrian Associated Charities; MGH Cancer Center Saltonstall Foundation; AstraZeneca FX The WGS was supported as part of the St Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project. We thank J. Lahti, J. Dalton and M. Valentine for help with FISH analysis, L. Holmfeldt, J. Zhang and M. Barbato for help with sample preparation, and V. Valentine for spectral karyotype analysis. We thank I. Qaddoumi, C. Rodriguez-Galindo and B. Haik for the support of the St Jude Children's Research Hospital retinoblastoma clinical research and W. Lei, D. McGoldrick, D. Alford, S. Espy, J. Obenauer and K. Johnson for assistance with data acquisition, handling and analysis. We thank A. McArthur and C. Guess for editing the manuscript, J. Temirov for help with sister chromatid analysis, J. Thurman for help with histology, F. Krafcik for help with cell culture, J. Wu and C. Billups for statistical analysis, J. Jeon for help with lentiviral preparations and C. Bradley for assistance with preclinical testing. This work was supported, in part, by Cancer Center Support (CA21765) from the NCI; grants to M. A. D. from the NIH (EY014867 and EY018599), the American Cancer Society and the Research to Prevent Blindness Foundation; and the American Lebanese Syrian Associated Charities. M. A. D. is a Howard Hughes Medical Institute Early Career Scientist. This work was also supported by an American Cancer Society Fellowship to A. L. M., the MGH Cancer Center Saltonstall Foundation Scholarship to N.J.D. and funding from AstraZeneca and NIH grants GM81607 and CA64402 to N.J.D. NR 32 TC 180 Z9 186 U1 4 U2 49 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 19 PY 2012 VL 481 IS 7381 BP 329 EP 334 DI 10.1038/nature10733 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 877VK UT WOS:000299210600035 PM 22237022 ER PT J AU Metallo, CM Gameiro, PA Bell, EL Mattaini, KR Yang, JJ Hiller, K Jewell, CM Johnson, ZR Irvine, DJ Guarente, L Kelleher, JK Vander Heiden, MG Iliopoulos, O Stephanopoulos, G AF Metallo, Christian M. Gameiro, Paulo A. Bell, Eric L. Mattaini, Katherine R. Yang, Juanjuan Hiller, Karsten Jewell, Christopher M. Johnson, Zachary R. Irvine, Darrell J. Guarente, Leonard Kelleher, Joanne K. Vander Heiden, Matthew G. Iliopoulos, Othon Stephanopoulos, Gregory TI Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia SO NATURE LA English DT Article ID FATTY-ACID SYNTHESIS; CELL-PROLIFERATION; FLUX ANALYSIS; HIF-ALPHA; GROWTH; CANCER; DEHYDROGENASE; SUPPRESSION; DISTRIBUTIONS; HYDROXYLATION AB Acetyl coenzyme A (AcCoA) is the central biosynthetic precursor for fatty-acid synthesis and protein acetylation. In the conventional view of mammalian cell metabolism, AcCoA is primarily generated from glucose-derived pyruvate through the citrate shuttle and ATP citrate lyase in the cytosol(1-3). However, proliferating cells that exhibit aerobic glycolysis and those exposed to hypoxia convert glucose to lactate at near-stoichiometric levels, directing glucose carbon away from the tricarboxylic acid cycle and fatty-acid synthesis(4). Although glutamine is consumed at levels exceeding that required for nitrogen biosynthesis(5), the regulation and use of glutamine metabolism in hypoxic cells is not well understood. Here we show that human cells use reductive metabolism of alpha-ketoglutarate to synthesize AcCoA for lipid synthesis. This isocitrate dehydrogenase-1 (IDH1)-dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived alpha-ketoglutarate for de novo lipogenesis. Furthermore, renal cell lines deficient in the von Hippel-Lindau tumour suppressor protein preferentially use reductive glutamine metabolism for lipid biosynthesis even at normal oxygen levels. These results identify a critical role for oxygen in regulating carbon use to produce AcCoA and support lipid synthesis in mammalian cells. C1 [Metallo, Christian M.; Gameiro, Paulo A.; Hiller, Karsten; Kelleher, Joanne K.; Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Gameiro, Paulo A.] Univ Coimbra, Dept Life Sci, P-3004517 Coimbra, Portugal. [Gameiro, Paulo A.; Yang, Juanjuan; Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Gameiro, Paulo A.; Yang, Juanjuan; Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Bell, Eric L.; Mattaini, Katherine R.; Guarente, Leonard; Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Mattaini, Katherine R.; Jewell, Christopher M.; Johnson, Zachary R.; Irvine, Darrell J.; Vander Heiden, Matthew G.] MIT, Koch Inst Canc Res, Cambridge, MA 02139 USA. [Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stephanopoulos, G (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. EM iliopoul@helix.mgh.harvard.edu; gregstep@mit.edu RI Bell, Eric/F-6368-2012 FU National Institutes of Health [R01 DK075850-01]; American Cancer Society; German Research Foundation (DFG) [HI1400]; Glenn Foundation for Medical Research; Burrough's Wellcome Fund; Smith Family; Damon Runyon Cancer Research Foundation; National Cancer Institute; Dana Farber/Harvard Cancer Center; [R01 CA122591] FX We thank N. Vokes and P. Ward for discussions. We also thank S. Gross and Agios Pharmaceuticals for providing the IDH1 construct. We acknowledge support from National Institutes of Health grant R01 DK075850-01. C. M. M. is supported by a postdoctoral fellowship from the American Cancer Society. K. H. is supported by the German Research Foundation (DFG) grant HI1400. L. G. is supported by the NIH and the Glenn Foundation for Medical Research. M. G. V. H. is supported by the Burrough's Wellcome Fund, the Smith Family, the Damon Runyon Cancer Research Foundation and the National Cancer Institute. D.J.I. is an investigator of the Howard Hughes Medical Institute. O.I. is supported by R01 CA122591 and the Dana Farber/Harvard Cancer Center Kidney SPORE Grant Developmental Award. NR 40 TC 406 Z9 411 U1 10 U2 139 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 19 PY 2012 VL 481 IS 7381 BP 380 EP U166 DI 10.1038/nature10602 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 877VK UT WOS:000299210600046 ER PT J AU Folmer, RL AF Folmer, Robert L. TI rTMS for tinnitus SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Editorial Material C1 Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR USA. RP Folmer, RL (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR USA. EM folmerr@ohsu.edu NR 3 TC 2 Z9 2 U1 0 U2 2 PU FRONTIERS RES FOUND PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD JAN 18 PY 2012 VL 6 AR 1 DI 10.3389/fnhum.2012.00001 PG 1 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 882LM UT WOS:000299565200001 PM 22279433 ER PT J AU Calias, P Papisov, M Pan, J Savioli, N Belov, V Huang, Y Lotterhand, J Alessandrini, M Liu, N Fischman, AJ Powell, JL Heartlein, MW AF Calias, Pericles Papisov, Mikhail Pan, Jing Savioli, Nancy Belov, Vasily Huang, Yan Lotterhand, Jason Alessandrini, Mary Liu, Nan Fischman, Alan J. Powell, Jan L. Heartlein, Michael W. TI CNS Penetration of Intrathecal-Lumbar Idursulfase in the Monkey, Dog and Mouse: Implications for Neurological Outcomes of Lysosomal Storage Disorder SO PLOS ONE LA English DT Article ID BLOOD-BRAIN-BARRIER; ENZYME REPLACEMENT THERAPY; II HUNTER-SYNDROME; GROWTH FACTOR-II/MANNOSE-6-PHOSPHATE RECEPTOR; ADENOASSOCIATED VIRUS VECTOR; CENTRAL-NERVOUS-SYSTEM; MUCOPOLYSACCHARIDOSIS-II; CEREBROSPINAL-FLUID; TRANSFERRIN RECEPTOR; MONOCLONAL-ANTIBODY AB A major challenge for the treatment of many central nervous system (CNS) disorders is the lack of convenient and effective methods for delivering biological agents to the brain. Mucopolysaccharidosis II (Hunter syndrome) is a rare inherited lysosomal storage disorder resulting from a deficiency of iduronate-2-sulfatase (I2S). I2S is a large, highly glycosylated enzyme. Intravenous administration is not likely to be an effective therapy for disease-related neurological outcomes that require enzyme access to the brain cells, in particular neurons and oligodendrocytes. We demonstrate that intracerebroventricular and lumbar intrathecal administration of recombinant I2S in dogs and nonhuman primates resulted in widespread enzyme distribution in the brain parenchyma, including remarkable deposition in the lysosomes of both neurons and oligodendrocytes. Lumbar intrathecal administration also resulted in enzyme delivery to the spinal cord, whereas little enzyme was detected there after intraventricular administration. Mucopolysaccharidosis II model is available in mice. Lumbar administration of recombinant I2S to enzyme deficient animals reduced the storage of glycosaminoglycans in both superficial and deep brain tissues, with concurrent morphological improvements. The observed patterns of enzyme transport from cerebrospinal fluid to the CNS tissues and the resultant biological activity (a) warrant further investigation of intrathecal delivery of I2S via lumbar catheter as an experimental treatment for the neurological symptoms of Hunter syndrome and (b) may have broader implications for CNS treatment with biopharmaceuticals. C1 [Calias, Pericles; Pan, Jing; Savioli, Nancy; Huang, Yan; Lotterhand, Jason; Alessandrini, Mary; Liu, Nan; Powell, Jan L.; Heartlein, Michael W.] Shire Human Genet Therapies Inc, Lexington, MA USA. [Papisov, Mikhail; Belov, Vasily] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Papisov, Mikhail; Belov, Vasily; Fischman, Alan J.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Papisov, Mikhail; Belov, Vasily; Fischman, Alan J.] Shriners Burns Hosp, Dept Nucl Med, Boston, MA USA. RP Calias, P (reprint author), Shire Human Genet Therapies Inc, Lexington, MA USA. EM pcalias@shire.com OI Papisov, Mikhail/0000-0003-4716-2122 FU Shire Human Genetic Therapies, Inc. FX This study was sponsored by Shire Human Genetic Therapies, Inc. The funders participated in the study design and conduct, data collection and analysis, decision to publish and preparation of the manuscript. NR 64 TC 41 Z9 41 U1 0 U2 5 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 JAN 18 PY 2012 VL 7 IS 1 AR e30341 DI 10.1371/journal.pone.0030341 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 885IH UT WOS:000299771900061 PM 22279584 ER PT J AU Monach, PA Kumpers, P Lukasz, A Tomasson, G Specks, U Stone, JH Cuthbertson, D Krischer, J Carette, S Ding, LN Hoffman, GS Ikle, D Kallenberg, CGM Khalidi, NA Langford, CA Seo, P St Clair, EW Spiera, R Tchao, N Ytterberg, SR Haubitz, M Merkel, PA AF Monach, Paul A. Kuempers, Philipp Lukasz, Alexander Tomasson, Gunnar Specks, Ulrich Stone, John H. Cuthbertson, David Krischer, Jeffrey Carette, Simon Ding, Linna Hoffman, Gary S. Ikle, David Kallenberg, Cees G. M. Khalidi, Nader A. Langford, Carol A. Seo, Philip St Clair, E. William Spiera, Robert Tchao, Nadia Ytterberg, Steven R. Haubitz, Marion Merkel, Peter A. TI Circulating Angiopoietin-2 as a Biomarker in ANCA-Associated Vasculitis SO PLOS ONE LA English DT Article ID SOLUBLE ADHESION MOLECULES; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; TIE-2 LIGAND ANGIOPOIETIN-2; CRITICALLY-ILL PATIENTS; C-REACTIVE PROTEIN; WEGENERS-GRANULOMATOSIS; E-SELECTIN; FOLLOW-UP; SYSTEMIC VASCULITIS; DISEASE-ACTIVITY AB The endothelial-specific Angiopoietin-Tie2 ligand-receptor system is an important regulator of endothelial activation. Binding of angiopoietin-2 (Ang-2) to Tie2 receptor renders the endothelial barrier responsive to pro-inflammatory cytokines. We previously showed that circulating Ang-2 correlated with disease severity in a small cohort of critically ill patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. The current study reassessed Ang-2 as a biomarker of disease activity and relapse in AAV. Circulating Ang-2 was measured in 162 patients with severe AAV (BVAS/WG >= 3, with or without glomerulonephritis) in a clinical trial. Ang-2 levels during active AAV were compared to levels in the same patients during remission (BVAS/WG = 0). Levels in clinical subsets of AAV were compared, and association with future disease course was assessed. Ang-2 levels were elevated in severe disease (median 3.0 ng/ml, interquartile range 1.9-4.4) compared to healthy controls (1.2, 0.9-1.5). However, they did not reliably decline with successful treatment (median 2.6 ng/ml, interquartile range 1.9-3.8, median change -0.1). Ang-2 correlated weakly with BVAS/WG score (r = 0.17), moderately with markers of systemic inflammation (r = 0.25-0.41), and inversely with renal function (r = -0.36). Levels were higher in patients with glomerulonephritis, but levels adjusted for renal dysfunction were no different in patients with or without glomerulonephritis. Levels were higher in patients with newly diagnosed AAV and lower in patients in whom treatment had recently been started. Ang-2 levels during active disease did not predict response to treatment, and Ang-2 levels in remission did not predict time to flare. Thus, Ang-2 appears to have limited practical value in AAV as a biomarker of disease activity at time of measurement or for predicting future activity. C1 [Monach, Paul A.; Tomasson, Gunnar; Merkel, Peter A.] Boston Univ, Rheumatol Sect, Dept Med, Sch Med,Vasculitis Ctr, Boston, MA 02215 USA. [Kuempers, Philipp; Lukasz, Alexander; Haubitz, Marion] Hannover Med Sch, Dept Hypertens & Nephrol, D-3000 Hannover, Germany. [Kuempers, Philipp] Univ Hosp Munster, Div Gen Internal Med Nephrol & Rheumatol, Dept Med, Munster, Germany. [Specks, Ulrich] Mayo Clin Coll Med, Div Pulm & Crit Care Med, Rochester, MN USA. [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Cuthbertson, David; Krischer, Jeffrey] Univ S Florida, Coll Med, Dept Pediat, Tampa, FL 33612 USA. [Carette, Simon] Univ Toronto, Div Rheumatol, Toronto, ON, Canada. [Ding, Linna] NIAID, Bethesda, MD 20892 USA. [Hoffman, Gary S.; Langford, Carol A.] Cleveland Clin, Ctr Vasculitis Care & Res, Cleveland, OH 44106 USA. [Ikle, David] Rho, Fed Syst Div, Chapel Hill, NC USA. [Kallenberg, Cees G. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Rheumatol & Clin Immunol, Groningen, Netherlands. [Khalidi, Nader A.] McMaster Univ, Div Rheumatol, Hamilton, ON, Canada. [Seo, Philip] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA. [St Clair, E. William] Duke Univ, Div Rheumatol & Immunol, Durham, NC USA. [Spiera, Robert] Hosp Special Surg, Div Rheumatol, New York, NY 10021 USA. [Tchao, Nadia] Immune Tolerance Network, San Francisco, CA USA. [Ytterberg, Steven R.] Mayo Clin Coll Med, Div Rheumatol, Rochester, MN USA. RP Monach, PA (reprint author), Boston Univ, Rheumatol Sect, Dept Med, Sch Med,Vasculitis Ctr, Boston, MA 02215 USA. EM pmonach@bu.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [U54AR057319, RC1 AR058303, P60 AR047785]; National Center for Research Resources [U54 RR019497]; National Institute of Neurological Disorders and Stroke [NS064808]; Office of Rare Diseases Research; NIH [N01 AI15416, M01 RR00533, K24 AR02224]; National Institute of Allergy and Infectious Diseases; Juvenile Diabetes Research Foundation; National Center for Research Resources (NCRR) [RR024150-01, RR025005, K24 AR049185, K23 AR052820]; Boston University [RR 025771]; Arthritis Foundation FX This work was sponsored by the Vasculitis Clinical Research Consortium which has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54AR057319, RC1 AR058303, and P60 AR047785), the National Center for Research Resources (U54 RR019497), the National Institute of Neurological Disorders and Stroke (NS064808), and the Office of Rare Diseases Research. The Rituximab in ANCA-Associated Vasculitis (RAVE) trial was performed with the support of the Immune Tolerance Network (NIH Contract #N01 AI15416), an international clinical research consortium supported by the National Institute of Allergy and Infectious Diseases and the Juvenile Diabetes Research Foundation. Genentech and Biogen Idec provided the study medications and partial funding of the clinical trial. For this ancillary study, Genentech had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. At the Mayo Clinic and Foundation, the trial was supported by a Clinical and Translational Science Award from the National Center for Research Resources (NCRR) (RR024150-01); at Johns Hopkins University, by grants from the NCRR (RR025005) and career development awards (K24 AR049185 to Dr. Stone, and K23 AR052820 to Dr. Seo); and at Boston University, by a Clinical and Translational Science Award (RR 025771), grants from the National Institutes of Health (M01 RR00533) and a career development award (K24 AR02224 to Dr. Merkel). Dr. Monach was also supported by an Arthritis Investigator Award from the Arthritis Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 5 Z9 5 U1 0 U2 4 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 JAN 18 PY 2012 VL 7 IS 1 AR e30197 DI 10.1371/journal.pone.0030197 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 885IH UT WOS:000299771900048 PM 22279570 ER PT J AU Vermeer, PD Bell, M Lee, K Vermeer, D Wieking, BG Bilal, E Bhanot, G Drapkin, RI Ganesan, S Klingelhutz, AJ Hendriks, WJ Lee, J AF Vermeer, Paola D. Bell, Megan Lee, Kimberly Vermeer, DanielW. Wieking, Byrant G. Bilal, Erhan Bhanot, Gyan Drapkin, Ronny I. Ganesan, Shridar Klingelhutz, Aloysius J. Hendriks, Wiljan J. Lee, Johnh. TI ErbB2, EphrinB1, Src Kinase and PTPN13 Signaling Complex Regulates MAP Kinase Signaling in Human Cancers SO PLOS ONE LA English DT Article ID HER-2 CODON-655 POLYMORPHISM; HUMAN-PAPILLOMAVIRUS TYPE-16; SQUAMOUS-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; HUMAN-BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; CLINICAL-IMPLICATIONS; TRANSMEMBRANE DOMAIN; INVASIVE GROWTH; EXPRESSION AB In non-cancerous cells, phosphorylated proteins exist transiently, becoming de-phosphorylated by specific phosphatases that terminate propagation of signaling pathways. In cancers, compromised phosphatase activity and/or expression occur and contribute to tumor phenotype. The non-receptor phosphatase, PTPN13, has recently been dubbed a putative tumor suppressor. It decreased expression in breast cancer correlates with decreased overall survival. Here we show that PTPN13 regulates a new signaling complex in breast cancer consisting of ErbB2, Src, and EphrinB1. To our knowledge, this signaling complex has not been previously described. Co-immunoprecipitation and localization studies demonstrate that EphrinB1, a PTPN13 substrate, interacts with ErbB2. In addition, the oncogenic V660E ErbB2 mutation enhances this interaction, while Src kinase mediates EphrinB1 phosphorylation and subsequent MAP Kinase signaling. Decreased PTPN13 function further enhances signaling. The association of oncogene kinases (ErbB2, Src), a signaling transmembrane ligand (EphrinB1) and a phosphatase tumor suppressor (PTPN13) suggest that EphrinB1 may be a relevant therapeutic target in breast cancers harboring ErbB2-activating mutations and decreased PTPN13 expression. C1 [Vermeer, Paola D.; Bell, Megan; Lee, Kimberly; Vermeer, DanielW.; Wieking, Byrant G.; Lee, Johnh.] Sanford Res Univ S Dakota, Canc Biol Res Ctr, Sioux Falls, SD USA. [Bilal, Erhan] IBM Res Corp, Thomas J Watson Res Ctr, Yorktown Hts, NY USA. [Bhanot, Gyan] Rutgers State Univ, Piscataway, NJ USA. [Drapkin, Ronny I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ganesan, Shridar] Canc Inst New Jersey, New Brunswick, NJ USA. [Klingelhutz, Aloysius J.] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. [Hendriks, Wiljan J.] Raboud Univ Nijmegen Med Ctr, NCMLS, Cell Biol Lab, Nijmegen, Netherlands. [Lee, Johnh.] Sanford Hlth, Dept Otolaryngol Head & Neck Surg, Sioux Falls, SD USA. RP Vermeer, PD (reprint author), Sanford Res Univ S Dakota, Canc Biol Res Ctr, Sioux Falls, SD USA. EM John.Lee@SanfordHealth.org RI Hendriks, Wiljan/A-5214-2013; Drapkin, Ronny/E-9944-2016 OI Hendriks, Wiljan/0000-0001-9481-8281; Drapkin, Ronny/0000-0002-6912-6977 FU National Institutes of Health/National Institute of Dental and Craniofacial Research [7R01DE018386-03]; State of South Dakota [3SB161] FX This work was supported by 7R01DE018386-03 from the National Institutes of Health/National Institute of Dental and Craniofacial Research and the State of South Dakota Translational Cancer sub-award 3SB161. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 13 Z9 13 U1 0 U2 10 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 JAN 18 PY 2012 VL 7 IS 1 AR e30447 DI 10.1371/journal.pone.0030447 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 885IH UT WOS:000299771900069 PM 22279592 ER PT J AU Lim, MA Selak, MA Xiang, Z Krainc, D Neve, RL Kraemer, BC Watts, JL Kalb, RG AF Lim, M. A. Selak, M. A. Xiang, Z. Krainc, D. Neve, R. L. Kraemer, B. C. Watts, J. L. Kalb, R. G. TI Reduced Activity of AMP-Activated Protein Kinase Protects against Genetic Models of Motor Neuron Disease SO JOURNAL OF NEUROSCIENCE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSGENIC MOUSE MODEL; HUNTINGTONS-DISEASE; SKELETAL-MUSCLE; CAENORHABDITIS-ELEGANS; CALORIC RESTRICTION; C-ELEGANS; LIFE-SPAN; IN-VIVO; MITOCHONDRIAL DYSFUNCTION AB A growing body of research indicates that amyotrophic lateral sclerosis (ALS) patients and mouse models of ALS exhibit metabolic dysfunction. A subpopulation of ALS patients possesses higher levels of resting energy expenditure and lower fat-free mass compared to healthy controls. Similarly, two mutant copper zinc superoxide dismutase 1 (mSOD1) mouse models of familial ALS possess a hypermetabolic phenotype. The pathophysiological relevance of the bioenergetic defects observed in ALS remains largely elusive. AMP-activated protein kinase (AMPK) is a key sensor of cellular energy status and thus might be activated in various models of ALS. Here, we report that AMPK activity is increased in spinal cord cultures expressing mSOD1, as well as in spinal cord lysates from mSOD1 mice. Reducing AMPK activity either pharmacologically or genetically prevents mSOD1-induced motor neuron death in vitro. To investigate the role of AMPK in vivo, we used Caenorhabditis elegans models of motor neuron disease. C. elegans engineered to express human mSOD1(G85R) in neurons develops locomotor dysfunction and severe fecundity defects when compared to transgenic worms expressing human wild-type SOD1. Genetic reduction of aak-2, the ortholog of the AMPK alpha 2 catalytic subunit in nematodes, improved locomotor behavior and fecundity in G85R animals. Similar observations were made with nematodes engineered to express mutant tat-activating regulatory (TAR) DNA-binding protein of 43 kDa molecular weight. Altogether, these data suggest that bioenergetic abnormalities are likely to be pathophysiologically relevant to motor neuron disease. C1 [Lim, M. A.; Kalb, R. G.] Childrens Hosp Philadelphia, Dept Pediat, Div Neurol, Abramson Res Ctr, Philadelphia, PA 19104 USA. [Kalb, R. G.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Lim, M. A.; Kalb, R. G.] Univ Penn, Neurosci Grad Grp, Philadelphia, PA 19104 USA. [Selak, M. A.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. [Xiang, Z.; Krainc, D.] MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Neve, R. L.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Kraemer, B. C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Fdn, Seattle, WA 98108 USA. [Kraemer, B. C.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Clin, Seattle, WA 98108 USA. [Watts, J. L.] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. RP Kalb, RG (reprint author), Childrens Hosp Philadelphia, Dept Pediat, Div Neurol, Abramson Res Ctr, Philadelphia, PA 19104 USA. EM kalb@email.chop.edu FU National Institutes of Health [F31NS06816502, R21NS060754, RO1NS052325]; Department of Veterans Affairs; ALS Association FX This work was supported by National Institutes of Health Grants F31NS06816502 (M. A. L.), R21NS060754, and RO1NS052325 (R. G. K.), the Department of Veterans Affairs (B. C. K.), and the ALS Association. We thank the generosity of Dr. Morris Birnbaum (University of Pennsylvania, Philadelphia, PA) for the AMPK wild-type and dominant negative plasmids; Dr. David Borchelt (University of Florida, Gainesville, FL) for the wild-type and mutant SOD1 plasmids; Drs. Arthur Horwich (Yale University, New Haven, CT) and Jiou Wang(Johns Hopkins University, Baltimore, MD) for the WT SOD1, G85R mSOD1, and G85R(line 18) worm strains; Dr. Hyeon-Sook Koo (Yonsei University, Seoul, South Korea) for the AAK2::GFP translational reporter strain; Drs. Martin Chalfie, Irini Topalidou, and Xiaoyin Chen (Columbia University, New York, NY) for the sid-1 mutant strains; Dr. Yishi Jin (University of California at San Diego, La Jolla, CA) for the CZ1200 strain; Dr. Miriam Goodman (Stanford University, Palo Alto, CA) for sharing the Parallel Worm Tracker program; and Drs. Gary Ruvkun (Harvard University, Cambridge, MA) and Todd Lamitina (University of Pennsylvania, Philadelphia, PA) for sharing RNAi clones. We acknowledge the Gene Knockout Consortium at Oklahoma Medical Research Center, which provided several of the C. elegans knock-out strains used in our experiments. We also acknowledge Jelena Mojsilovic-Petrovic, Heather Pratt, Peter Krumbhaar, and Daniel Helbig for their excellent technical assistance. Finally, we thank the C. elegans laboratories at the University of Pennsylvania (Christopher Fang-Yen, Todd Lamitina, John Murray, David Raizen, and Meera Sundaram) for their advice and suggestions. NR 97 TC 41 Z9 43 U1 0 U2 9 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 JAN 18 PY 2012 VL 32 IS 3 BP 1123 EP 1141 DI 10.1523/JNEUROSCI.6554-10.2012 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 879JG UT WOS:000299324900036 PM 22262909 ER PT J AU Clark, RA Watanabe, R Teague, JE Schlapbach, C Tawa, MC Adams, N Dorosario, AA Chaney, KS Cutler, CS LeBoeuf, NR Carter, JB Fisher, DC Kupper, TS AF Clark, Rachael A. Watanabe, Rei Teague, Jessica E. Schlapbach, Christoph Tawa, Marianne C. Adams, Natalie Dorosario, Andrew A. Chaney, Keri S. Cutler, Corey S. LeBoeuf, Nicole R. Carter, Joi B. Fisher, David C. Kupper, Thomas S. TI Skin Effector Memory T Cells Do Not Recirculate and Provide Immune Protection in Alemtuzumab-Treated CTCL Patients SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID MYCOSIS FUNGOIDES/SEZARY-SYNDROME; REFRACTORY SEZARY-SYNDROME; MONOCLONAL-ANTIBODY; LYMPHOPROLIFERATIVE DISORDERS; CYTOKINE PRODUCTION; PHASE-II; LYMPHOMA; THERAPY; CAMPATH-1H; RESIDENT AB Cutaneous T cell lymphoma (CTCL) is a cancer of skin-homing T cells with variants that include leukemic CTCL (L-CTCL), a malignancy of central memory T cells (T(CM)), and mycosis fungoides (MF), a malignancy of skin resident effector memory T cells (T(EM)). We report that low-dose alemtuzumab (alpha CD52) effectively treated patients with refractory L-CTCL but not MF. Alemtuzumab depleted all T cells in blood and depleted both benign and malignant T(CM) from skin, but a diverse population of skin resident T(EM) remained in skin after therapy. T cell depletion with alemtuzumab required the presence of neutrophils, a cell type frequent in blood but rare in normal skin. These data suggest that T(CM) were depleted because they recirculate between the blood and the skin, whereas skin resident T(EM) were spared because they are sessile and non-recirculating. After alemtuzumab treatment, skin T cells produced lower amounts of interleukin-4 and higher amounts of interferon-gamma. Moreover, there was a marked lack of infections in alemtuzumab-treated L-CTCL patients despite the complete absence of T cells in the blood, suggesting that skin resident T(EM) can protect the skin from pathogens even in the absence of T cell recruitment from the circulation. Together, these data suggest that alemtuzumab may treat refractory L-CTCL without severely compromising the immune response to infection by depleting circulating T(CM) but sparing the skin resident T(EM) that provide local immune protection of the skin. C1 [Clark, Rachael A.; Watanabe, Rei; Teague, Jessica E.; Schlapbach, Christoph; Chaney, Keri S.; LeBoeuf, Nicole R.; Kupper, Thomas S.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Clark, Rachael A.; Watanabe, Rei; Teague, Jessica E.; Schlapbach, Christoph; Chaney, Keri S.; LeBoeuf, Nicole R.; Kupper, Thomas S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Clark, Rachael A.; Tawa, Marianne C.; Adams, Natalie; Dorosario, Andrew A.; Cutler, Corey S.; Fisher, David C.; Kupper, Thomas S.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Carter, Joi B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Clark, RA (reprint author), Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA. EM rclark1@partners.org RI Schlapbach, Christoph/D-5832-2013 OI Schlapbach, Christoph/0000-0003-0258-1243 FU Damon Runyon Clinical Investigator Award [R01 AR056720]; NIH/National Cancer Institute [P50 CA9368305]; NIH/National Institute of Allergy and Infectious Diseases [R01 A1025082]; Swiss National Science Foundation; Fondation Rene Touraine FX This work was supported by a charitable contribution from Edward P. Lawrence, Esq.; a Damon Runyon Clinical Investigator Award (to R.A.C.) and R01 AR056720 (to R.A.C.); and the SPORE in Skin Cancer P50 CA9368305 NIH/National Cancer Institute (to T.S.K.) and R01 A1025082 NIH/National Institute of Allergy and Infectious Diseases (to T.S.K.). Salary support for C.S. was provided by the Swiss National Science Foundation and the Fondation Rene Touraine. NR 51 TC 37 Z9 37 U1 1 U2 4 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 JAN 18 PY 2012 VL 4 IS 117 AR 117ra7 DI 10.1126/scitranslmed.3003008 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 879JR UT WOS:000299326000003 PM 22261031 ER PT J AU Lee-Lewandrowski, E Chang, C Gregory, K Lewandrowski, K AF Lee-Lewandrowski, Elizabeth Chang, Connie Gregory, Kimberly Lewandrowski, Kent TI Evaluation of rapid point-of-care creatinine testing in the radiology service of a large academic medical center: Impact on clinical operations and patient disposition SO CLINICA CHIMICA ACTA LA English DT Article DE Point-of-care testing; Creatinine; Outcomes; Contrast induced nephropathy; Nephrogenic systemic fibrosis ID EMERGENCY-DEPARTMENT; IMPLEMENTATION; STAY AB Background: Measurement of creatinine and calculation of the estimated glomerular filtration rate (eGFR) are widely employed to identify patients with chronic kidney disease who are at risk for contrast induced acute kidney injury and nephrogenic systemic fibrosis. However, patients may present for radiologic studies without a recent creatinine/eGFR necessitating cancelation of the study or performance of the scan without contrast. Both of these approaches are suboptimal. Methods: We implemented a rapid whole blood point-of-care (POCT) creatinine test (iSTAT, Abbott Point-of-Care) in our radiology department and assessed the impact on clinical operations. Results: Over a 7-month period a total of 3087 creatinine tests were performed. Overall 53% of patients presenting for scans (441/month) did not have a recent eGFR. An audit of 1 month of creatinine/eGFR values showed that 74% were normal permitting the scan to be performed without further consideration. Of the abnormal values 74% were performed with contrast and 26% without. Of note 78% of patients with an abnormal eGFR had a normal creatinine value. The cost of the POC test was $10.06 compared to a cost of $5.32 (including phlebotomy) for a creatinine performed in the central laboratory. The added incremental cost for the POC test was therefore $4.74. Conclusions: Determining the cost effectiveness of the rapid test is extremely challenging because the analysis would need to take many complex factors into consideration including the effect on workflow in the radiology department, the clinical impact of more timely scans, the clinical and financial consequences of performing scans with or without contrast and the impact on revenues complicated by differential reimbursement rates and payor mix. However, given the benefits of the test on radiology operations and on the quality and timeliness of care it appears that the POCT test is cost effective and improves clinical operations. (C) 2011 Elsevier B.V. All rights reserved. C1 [Lee-Lewandrowski, Elizabeth; Gregory, Kimberly; Lewandrowski, Kent] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chang, Connie] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Gray 5 Chem, Boston, MA 02114 USA. EM klewandrowski@partners.org FU Abbott Point-of-Care FX This study was supported in part by a grant from Abbott Point-of-Care. NR 10 TC 12 Z9 12 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN 18 PY 2012 VL 413 IS 1-2 BP 88 EP 92 DI 10.1016/j.cca.2011.05.006 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 867NZ UT WOS:000298462400012 PM 21600893 ER PT J AU Cannuscio, CC AF Cannuscio, Carolyn C. TI Lessons in Elder Care SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, Philadelphia VA Med Ctr,Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. RP Cannuscio, CC (reprint author), Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, Philadelphia VA Med Ctr,Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. EM carolyncannu@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 18 PY 2012 VL 307 IS 3 BP 263 EP 264 DI 10.1001/jama.2011.2004 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 877EY UT WOS:000299161200021 PM 22253392 ER PT J AU Zhang, XC Wang, Z Zhang, XY Le, MH Sun, JG Xu, D Cheng, JL Stacey, G AF Zhang, Xue-Cheng Wang, Zheng Zhang, Xinyan Le, Mi Ha Sun, Jianguo Xu, Dong Cheng, Jianlin Stacey, Gary TI Evolutionary dynamics of protein domain architecture in plants SO BMC EVOLUTIONARY BIOLOGY LA English DT Article DE domain architecture; evolutionary dynamics; plant lineage; genetic origin ID EUKARYOTIC EVOLUTION; GENOME EVOLUTION; HISTORY; REARRANGEMENTS; DUPLICATIONS; COMBINATIONS; PREDICTION; PHYLOGENY; SEQUENCE; PROTEOMES AB Background: Protein domains are the structural, functional and evolutionary units of the protein. Protein domain architectures are the linear arrangements of domain(s) in individual proteins. Although the evolutionary history of protein domain architecture has been extensively studied in microorganisms, the evolutionary dynamics of domain architecture in the plant kingdom remains largely undefined. To address this question, we analyzed the lineage-based protein domain architecture content in 14 completed green plant genomes. Results: Our analyses show that all 14 plant genomes maintain similar distributions of species-specific, single-domain, and multi-domain architectures. Approximately 65% of plant domain architectures are universally present in all plant lineages, while the remaining architectures are lineage-specific. Clear examples are seen of both the loss and gain of specific protein architectures in higher plants. There has been a dynamic, lineage-wise expansion of domain architectures during plant evolution. The data suggest that this expansion can be largely explained by changes in nuclear ploidy resulting from rounds of whole genome duplications. Indeed, there has been a decrease in the number of unique domain architectures when the genomes were normalized into a presumed ancestral genome that has not undergone whole genome duplications. Conclusions: Our data show the conservation of universal domain architectures in all available plant genomes, indicating the presence of an evolutionarily conserved, core set of protein components. However, the occurrence of lineage-specific domain architectures indicates that domain architecture diversity has been maintained beyond these core components in plant genomes. Although several features of genome-wide domain architecture content are conserved in plants, the data clearly demonstrate lineage-wise, progressive changes and expansions of individual protein domain architectures, reinforcing the notion that plant genomes have undergone dynamic evolution. C1 [Zhang, Xue-Cheng; Le, Mi Ha; Stacey, Gary] Univ Missouri, Div Plant Sci, Columbia, MO 65211 USA. [Wang, Zheng; Xu, Dong; Cheng, Jianlin] Univ Missouri, Dept Comp Sci, Columbia, MO 65211 USA. [Zhang, Xinyan; Sun, Jianguo] Univ Missouri, Dept Stat, Columbia, MO 65211 USA. [Xu, Dong; Cheng, Jianlin] Univ Missouri, Inst Informat, Columbia, MO 65211 USA. [Stacey, Gary] Univ Missouri, Div Biochem, Natl Ctr Soybean Biotechnol, Ctr Sustainable Energy, Columbia, MO 65211 USA. [Zhang, Xue-Cheng] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Zhang, Xue-Cheng] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Zhang, Xinyan] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Zhang, XC (reprint author), Univ Missouri, Div Plant Sci, Columbia, MO 65211 USA. EM xzhang@molbio.mgh.harvard.edu FU Paul K. and Diane Shumaker Endowment in Bioinformatics; US Department of Energy, Office of Science [DE-FG02-02ER15309]; Biological and Environmental Research Program [DE-SC0004898]; UM research board; MU research council; NIH [1R010GM93123]; United Soybean Board FX We thank Dr. Steven B. Cannon, Dr. Melanie R. Mormile and Dr. Seth D. Findley for critical reading of the manuscript. ZW is supported in part by the Paul K. and Diane Shumaker Endowment in Bioinformatics. This work was funded grants from the US Department of Energy, Office of Science, Basic Energy Biosciences Program (grant No. DE-FG02-02ER15309 to GS) and from the Biological and Environmental Research Program (grant No. DE-SC0004898 to GS, DX, and JC), a UM research board grant, a MU research council grant and a NIH grant (1R010GM93123) to JC, and a United Soybean Board grant to XD. NR 43 TC 10 Z9 10 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD JAN 17 PY 2012 VL 12 AR 6 DI 10.1186/1471-2148-12-6 PG 12 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 913PM UT WOS:000301889900001 PM 22252370 ER PT J AU Noerholm, M Balaj, L Limperg, T Salehi, A Zhu, LD Hochberg, FH Breakefield, XO Carter, BS Skog, J AF Noerholm, Mikkel Balaj, Leonora Limperg, Tobias Salehi, Afshin Zhu, Lin Dan Hochberg, Fred H. Breakefield, Xandra O. Carter, Bob S. Skog, Johan TI RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls SO BMC CANCER LA English DT Article DE Exosomes; Microvesicles; Microarray; Biomarkers; Serum; Glioma ID PERIPHERAL-BLOOD CELLS; DIAGNOSTIC BIOMARKERS; COLORECTAL-CANCER; BREAST-CANCER; EXOSOMES; PLASMA; MICROARRAY; PROFILES; PROTEINS; VESICLES AB Background: RNA from exosomes and other microvesicles contain transcripts of tumour origin. In this study we sought to identify biomarkers of glioblastoma multiforme in microvesicle RNA from serum of affected patients. Methods: Microvesicle RNA from serum from patients with de-novo primary glioblastoma multiforme (N = 9) and normal controls (N = 7) were analyzed by microarray analysis. Samples were collected according to protocols approved by the Institutional Review Board. Differential expressions were validated by qRT-PCR in a separate set of samples (N = 10 in both groups). Results: Expression profiles of microvesicle RNA correctly separated individuals in two groups by unsupervised clustering. The most significant differences pertained to down-regulated genes (121 genes > 2-fold down) in the glioblastoma multiforme patient microvesicle RNA, validated by qRT-PCR on several genes. Overall, yields of microvesicle RNA from patients was higher than from normal controls, but the additional RNA was primarily of size < 500 nt. Gene ontology of the down-regulated genes indicated these are coding for ribosomal proteins and genes related to ribosome production. Conclusions: Serum microvesicle RNA from patients with glioblastoma multiforme has significantly down-regulated levels of RNAs coding for ribosome production, compared to normal healthy controls, but a large overabundance of RNA of unknown origin with size < 500 nt. C1 [Noerholm, Mikkel; Balaj, Leonora; Limperg, Tobias; Salehi, Afshin; Zhu, Lin Dan; Hochberg, Fred H.; Breakefield, Xandra O.; Carter, Bob S.; Skog, Johan] Massachusetts Gen Hosp, Dept Neurol Neurosurg & Radiol, Boston, MA 02114 USA. [Noerholm, Mikkel; Balaj, Leonora; Limperg, Tobias; Salehi, Afshin; Zhu, Lin Dan; Hochberg, Fred H.; Breakefield, Xandra O.; Carter, Bob S.; Skog, Johan] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Noerholm, Mikkel; Skog, Johan] Columbia Univ, Med Ctr, Exosome Diagnost Inc, New York, NY 10032 USA. [Limperg, Tobias] Univ Med Ctr Utrecht, Dept Neurosci & Pharmacol, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. [Salehi, Afshin; Carter, Bob S.] UCSD Sch Med, Div Neurol Surg, San Diego, CA 92103 USA. RP Noerholm, M (reprint author), Massachusetts Gen Hosp, Dept Neurol Neurosurg & Radiol, Boston, MA 02114 USA. EM mikkel@exosomedx.com FU American Brain Tumor Association; NIH/NCI [CA141226, CA156009, CA069246]; PHS [P30NS045776] FX We would like to thank Lori LoGuidice for kind assistance with RNA extractions and Suzanne McDavitt for review and formatting of themanuscript. This work was funded by American Brain Tumor Association Translational grant (JS, LB), NIH/NCI grant CA141226 (XOB), CA156009 (XOB) and NIH/NCI grant CA069246 (BC, AS and FHH). Brain Tumor Funders Collaborative and Harvard Catalyst (BSC). We gratefully acknowledge the Neuroscience Center PCR Core facility, which is funded by PHS grant P30NS045776. NR 41 TC 74 Z9 76 U1 2 U2 23 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 JAN 17 PY 2012 VL 12 AR 22 DI 10.1186/1471-2407-12-22 PG 11 WC Oncology SC Oncology GA 907ND UT WOS:000301423700001 PM 22251860 ER PT J AU Liu, J Lee, GY Lawitts, JA Toner, M Biggers, JD AF Liu, Jie Lee, Gloria Y. Lawitts, Joel A. Toner, Mehmet Biggers, John D. TI Preservation of Mouse Sperm by Convective Drying and Storing in 3-O-Methyl-D-Glucose SO PLOS ONE LA English DT Article ID DESICCATION TOLERANCE; SPERMATOZOA; TRANSPORT; TEMPERATURE; FERTILIZATION; HEPATOCYTES; CHROMOSOMES; EXPRESSION; INTEGRITY; CHROMATIN AB With the fast advancement in the genetics and bio-medical fields, the vast number of valuable transgenic and rare genetic mouse models need to be preserved. Preservation of mouse sperm by convective drying and subsequent storing at above freezing temperatures could dramatically reduce the cost and facilitate shipping. Mouse sperm were convectively dried under nitrogen gas in the Na-EGTA solution containing 100 mmol/L 3-O-methyl-D-glucose and stored in LiCl sorption jars (Relative Humidity, RH, 12%) at 4 degrees C and 22 degrees C for up to one year. The functionality of these sperm samples after storage was tested by intracytoplasmic injection into mouse oocytes. The percentages of blastocysts produced from sperm stored at 4 degrees C for 1, 2, 3, 6, and 12 months were 62.6%, 53.4%, 39.6%, 33.3%, and 30.4%, respectively, while those stored at 22 degrees C for 1, 2, and 3 months were 28.8%, 26.6%, and 12.2%, respectively. Transfer of 38 two-to four-cell embryos from sperm stored at 4 degrees C for 1 year produced two live pups while 59 two-to four-cell embryos from sperm stored at 22 degrees C for 3 months also produced two live pups. Although all the pups looked healthy at 3 weeks of age, normality of offspring produced using convectively dried sperm needs further investigation. The percentages of blastocyst from sperm stored in the higher relative humidity conditions of NaBr and MgCl2 jars and driest condition of P2O5 jars at 4 degrees C and 22 degrees C were all lower. A simple method of mouse sperm preservation is demonstrated. Three-O-methyl-D-glucose, a metabolically inactive derivative of glucose, offers significant protection for dried mouse sperm at above freezing temperatures without the need for poration of cell membrane. C1 [Liu, Jie; Lee, Gloria Y.; Toner, Mehmet; Biggers, John D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02115 USA. [Liu, Jie; Lee, Gloria Y.; Toner, Mehmet; Biggers, John D.] Shriners Hosp Children, Boston, MA USA. [Lawitts, Joel A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Biggers, John D.] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA USA. RP Liu, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02115 USA. EM jliu22@partners.org FU National Institutes of Health; National Center for Research Resources [NIH/NCRR 5 R24 RR018934] FX The authors would like to thank funding support from the National Institutes of Health and the National Center for Research Resources (NIH/NCRR 5 R24 RR018934). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 5 Z9 5 U1 0 U2 7 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 JAN 17 PY 2012 VL 7 IS 1 AR e29924 DI 10.1371/journal.pone.0029924 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 907XU UT WOS:000301454400040 PM 22272261 ER PT J AU Shanmugasundararaj, S Lehle, S Yamodo, HI Husain, SS Tseng, C Nguyen, K Addona, GH Miller, KW AF Shanmugasundararaj, Sivananthaperumal Lehle, Simon Yamodo, Herve I. Husain, S. Shaukat Tseng, Claire Nguyen, Khanh Addona, George H. Miller, Keith W. TI The Location and Nature of General Anesthetic Binding Sites on the Active Conformation of Firefly Luciferase; A Time Resolved Photolabeling Study SO PLOS ONE LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; COMPETITIVE-BINDING; PHASE-TRANSITION; STRUCTURAL BASIS; MOLECULAR-BASIS; DIETHYL-ETHER; IN-VITRO; INHIBITION; SYSTEM; BIOLUMINESCENCE AB Firefly luciferase is one of the few soluble proteins that is acted upon by a wide variety of general anesthetics and alcohols; they inhibit the ATP-driven production of light. We have used time-resolved photolabeling to locate the binding sites of alcohols during the initial light output, some 200 ms after adding ATP. The photolabel 3-azioctanol inhibited the initial light output with an IC50 of 200 mu M, close to its general anesthetic potency. Photoincorporation of [H-3]3-azioctanol into luciferase was saturable but weak. It was enhanced 200 ms after adding ATP but was negligible minutes later. Sequencing of tryptic digests by HPLC-MSMS revealed a similar conformation-dependence for photoincorporation of 3-azioctanol into Glu-313, a residue that lines the bottom of a deep cleft (vestibule) whose outer end binds luciferin. An aromatic diazirine analog of benzyl alcohol with broader side chain reactivity reported two sites. First, it photolabeled two residues in the vestibule, Ser-286 and Ile-288, both of which are implicated with Glu-313 in the conformation change accompanying activation. Second, it photolabeled two residues that contact luciferin, Ser-316 and Ser-349. Thus, time resolved photolabeling supports two mechanisms of action. First, an allosteric one, in which anesthetics bind in the vestibule displacing water molecules that are thought to be involved in light output. Second, a competitive one, in which anesthetics bind isosterically with luciferin. This work provides structural evidence that supports the competitive and allosteric actions previously characterized by kinetic studies. C1 [Shanmugasundararaj, Sivananthaperumal; Lehle, Simon; Yamodo, Herve I.; Husain, S. Shaukat; Nguyen, Khanh; Addona, George H.; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Tseng, Claire; Addona, George H.; Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Shanmugasundararaj, S (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM k_miller@helix.mgh.harvard.edu FU United States Public Health Service [GM 069726, 058448]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital FX This research was supported by grants from the United States Public Health Service to KM (GM 069726 & 058448) and by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; We thank Elizabeth Kelly for assistance with the anesthetic potency measurements. Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 RR-01081) [32]. NR 32 TC 4 Z9 4 U1 0 U2 13 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 JAN 17 PY 2012 VL 7 IS 1 AR e29854 DI 10.1371/journal.pone.0029854 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 907XU UT WOS:000301454400032 PM 22272253 ER PT J AU Vathipadiekal, V Saxena, D Mok, SC Hauschka, PV Ozbun, L Birrer, MJ AF Vathipadiekal, Vinod Saxena, Deepa Mok, Samuel C. Hauschka, Peter V. Ozbun, Laurent Birrer, Michael J. TI Identification of a Potential Ovarian Cancer Stem Cell Gene Expression Profile from Advanced Stage Papillary Serous Ovarian Cancer SO PLOS ONE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; DRUG EFFLUX CAPACITY; SIDE POPULATION; HEMATOPOIETIC STEM; INITIATING CELLS; SOLID TUMORS; SURVIVAL; PHENOTYPE; NOTCH; CARCINOMA AB Identification of gene expression profiles of cancer stem cells may have significant implications in the understanding of tumor biology and for the design of novel treatments targeted toward these cells. Here we report a potential ovarian cancer stem cell gene expression profile from isolated side population of fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma. Affymetrix U133 Plus 2.0 microarrays were used to interrogate the differentially expressed genes between side population (SP) and main population (MP), and the results were analyzed by paired T-test using BRB-ArrayTools. We identified 138 up-regulated and 302 down-regulated genes that were differentially expressed between all 10 SP/MP pairs. Microarray data was validated using qRT-PCR and17/19 (89.5%) genes showed robust correlations between microarray and qRT-PCR expression data. The Pathway Studio analysis identified several genes involved in cell survival, differentiation, proliferation, and apoptosis which are unique to SP cells and a mechanism for the activation of Notch signaling is identified. To validate these findings, we have identified and isolated SP cells enriched for cancer stem cells from human ovarian cancer cell lines. The SP populations were having a higher colony forming efficiency in comparison to its MP counterpart and also capable of sustained expansion and differentiation in to SP and MP phenotypes. 50,000 SP cells produced tumor in nude mice whereas the same number of MP cells failed to give any tumor at 8 weeks after injection. The SP cells demonstrated a dose dependent sensitivity to specific c-secretase inhibitors implicating the role of Notch signaling pathway in SP cell survival. Further the generated SP gene list was found to be enriched in recurrent ovarian cancer tumors. C1 [Vathipadiekal, Vinod; Birrer, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Saxena, Deepa; Hauschka, Peter V.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Orthopaed Surg, Boston, MA USA. [Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Ozbun, Laurent] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Vathipadiekal, V (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. EM mbirrer@partners.org OI Vathipadiekal, Vinod/0000-0002-8181-6890 FU National Institutes of the Health [5R01CA142832-02 216288 2009A051746, 1RC4CA156551-01 217168 2010A053125]; National Cancer Institute; CDMRP-DOD [W81XWH-06-1-0422, W81XWH-09-1-0292]; Susan G. Komen for the Cure [BCTR 0600935]; Orthopaedic Surgery Foundation, Children's Hospital Boston FX This work was supported in part by grants from National Institutes of the Health (5R01CA142832-02 216288 2009A051746, 1RC4CA156551-01 217168 2010A053125 and an Intramural Research Program of the National Cancer Institute) to MJB. PVH and DS were supported by grants from the CDMRP-DOD (W81XWH-06-1-0422 and W81XWH-09-1-0292), Susan G. Komen for the Cure (BCTR 0600935), and the Orthopaedic Surgery Foundation, Children's Hospital Boston. 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 65 TC 43 Z9 44 U1 1 U2 6 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 JAN 17 PY 2012 VL 7 IS 1 AR e29079 DI 10.1371/journal.pone.0029079 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 907XU UT WOS:000301454400006 PM 22272227 ER PT J AU Iezzoni, LI AF Iezzoni, Lisa I. TI Mobilizing to Address Increasing Population Disability SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 17 PY 2012 VL 156 IS 2 BP 160 EP 161 DI 10.7326/0003-4819-156-2-201201170-00015 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 894IW UT WOS:000300421400010 PM 22250150 ER PT J AU Bovenberg, MSS Degeling, MH Tannous, BA AF Bovenberg, M. Sarah S. Degeling, M. Hannah Tannous, Bakhos A. TI Enhanced Gaussia Luciferase Blood Assay for Monitoring of in Vivo Biological Processes SO ANALYTICAL CHEMISTRY LA English DT Article ID GENE-EXPRESSION; ER STRESS; CULTURE; CELLS AB Secreted Gaussia luciferase (Gluc) has been shown to be a useful tool for ex vivo monitoring of in vivo biological processes. The Gluc level in the blood was used to detect tumor growth, metastasis and response to therapy, gene transfer, and circulating cells viability, as well as transcription factors activation, complementing in vivo bioluminescence imaging. The sensitivity of the Gluc blood assay is limited due to the absorption of blue light by pigmented molecules such as hemoglobin, resulting in quenching of the signal and therefore lower sensitivity. To overcome this problem, we designed an alternative microtiter well-based binding assay in which Gluc is captured first from blood using a specific antibody followed by the addition of coelenterazine and signal acquisition using a luminometer. This assay showed to be over 1 order of magnitude more sensitive in detecting Gluc in the blood as compared to the direct Gluc blood assay enhancing ex vivo monitoring of biological processes. C1 [Bovenberg, M. Sarah S.; Degeling, M. Hannah; Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Charlestown, MA 02129 USA. [Bovenberg, M. Sarah S.; Degeling, M. Hannah; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Bovenberg, M. Sarah S.; Degeling, M. Hannah] Leiden Univ, Med Ctr, Dept Neurosurg, Leiden, Netherlands. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU NIH/NCI [4R00CA126839]; NIH/NINDS [P30NS045776, 1R01NS064983]; Fulbright scholarship; Saal van Zwanenberg Foundation; VSB fonds; Dr. Hendrik Muller Vaderlandschfonds; Dutch Cancer Foundation (KWF Kankerbestrijding); Hersenstichting brain fund; Jo Keur (Leiden hospital); Huygens Scholarship Program; Jo Keur FX M.S.S.B. and M.H.D. contributed equally to this work. This work was supported by grants from NIH/NCI 4R00CA126839 and NIH/NINDS P30NS045776 and 1R01NS064983 (B.A.T.). M.H.D. is supported by a Fulbright scholarship, the Saal van Zwanenberg Foundation, VSB fonds, Dr. Hendrik Muller Vaderlandschfonds, the Dutch Cancer Foundation (KWF Kankerbestrijding), and the Hersenstichting brain fund as well as the Jo Keur (Leiden hospital). M.S.S.B. was supported by a Fulbright scholarship, the Huygens Scholarship Program, VSB fonds, Jo Keur, and the Saal van Zwanenberg Foundation. We would like to thank Dr. Jian Teng for technical assistance. NR 16 TC 5 Z9 6 U1 2 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JAN 17 PY 2012 VL 84 IS 2 BP 1189 EP 1192 DI 10.1021/ac202833r PG 4 WC Chemistry, Analytical SC Chemistry GA 876UY UT WOS:000299134400067 PM 22148161 ER PT J AU Roti, G Stegmaier, K AF Roti, G. Stegmaier, K. TI Genetic and proteomic approaches to identify cancer drug targets SO BRITISH JOURNAL OF CANCER LA English DT Review DE drug discovery; protein target identification; chemical genomics; chemical proteomics; small-molecule library screening; cancer drug targets ID DIVERSITY-ORIENTED SYNTHESIS; SMALL-MOLECULE MICROARRAYS; EXPRESSION PROFILES; CHEMICAL PROTEOMICS; CONNECTIVITY MAP; LEUKEMIA STEM; DISCOVERY; CELLS; DIFFERENTIATION; IDENTIFICATION AB While target-based small-molecule discovery has taken centre-stage in the pharmaceutical industry, there are many cancer-promoting proteins not easily addressed with a traditional target-based screening approach. In order to address this problem, as well as to identify modulators of biological states in the absence of knowing the protein target of the state switch, alternative phenotypic screening approaches, such as gene expression-based and high-content imaging, have been developed. With this renewed interest in phenotypic screening, however, comes the challenge of identifying the binding protein target(s) of small-molecule hits. Emerging technologies have the potential to improve the process of target identification. In this review, we discuss the application of genomic (gene expression-based), genetic (short hairpin RNA and open reading frame screening), and proteomic approaches to protein target identification. British Journal of Cancer (2012) 106, 254-261. doi:10.1038/bjc.2011.543 www.bjcancer.com Published online 13 December 2011 (C) 2012 Cancer Research UK C1 [Roti, G.; Stegmaier, K.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02215 USA. [Roti, G.; Stegmaier, K.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02215 USA. [Stegmaier, K.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. [Stegmaier, K.] MIT, Cambridge, MA 02142 USA. RP Stegmaier, K (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02215 USA. EM kimberly_stegmaier@dfci.harvard.edu FU EHA-ASH; American-Italian Cancer Foundation; Lady Tata Memorial Trust; Leukemia and Lymphoma Society; National Cancer Institute; American Cancer Society; Howard Hughes Medical Institute; Stand-up-to-Cancer FX This work was supported by the EHA-ASH, American-Italian Cancer Foundation, Lady Tata Memorial Trust, and Leukemia and Lymphoma Society Special Fellow award (GR); and by the National Cancer Institute, American Cancer Society, Howard Hughes Medical Institute, and Stand-up-to-Cancer (KS). We thank Aaron Thorner and Justin Lamb for their critical reading of the paper. NR 45 TC 11 Z9 11 U1 0 U2 11 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 JAN 17 PY 2012 VL 106 IS 2 BP 254 EP 261 DI 10.1038/bjc.2011.543 PG 8 WC Oncology SC Oncology GA 879HU UT WOS:000299321100004 PM 22166799 ER PT J AU Leitch, JM Li, CX Baron, JA Matthews, LM Cao, XH Hart, PJ Culotta, VC AF Leitch, Jeffry M. Li, Cissy X. Baron, J. Allen Matthews, Lauren M. Cao, Xiaohang Hart, P. John Culotta, Valeria C. TI Post-Translational Modification of Cu/Zn Superoxide Dismutase under Anaerobic Conditions SO BIOCHEMISTRY LA English DT Article ID COPPER CHAPERONE CCS; AMYOTROPHIC-LATERAL-SCLEROSIS; SACCHAROMYCES-CEREVISIAE; CU,ZN-SUPEROXIDE DISMUTASE; CAENORHABDITIS-ELEGANS; OXYGEN; YEAST; ACTIVATION; METAL; PATHWAY AB In eukaryotic organisms, the largely cytosolic copper- and zinc-containing superoxide dismutase (Cu/Zn SOD) enzyme represents a key defense against reactive oxygen toxicity. Although much is known about the biology of this enzyme under aerobic conditions, less is understood regarding the effects of low oxygen levels on Cu/Zn SOD enzymes from diverse organisms. We show here that like bakers' yeast (Saccharomyces cerevisiae), adaptation of the multicellular Caenorhabditis elegans to growth at low oxygen levels involves strong downregulation of its Cu/Zn SOD. Much of this regulation occurs at the post-translational level where CCS-independent activation of Cu/Zn SOD is inhibited. Hypoxia inactivates the endogenous Cu/Zn SOD of C. elegans Cu/Zn SOD as well as a P144 mutant of S. cerevisiae Cu/Zn SOD (herein denoted Sod1p) that is independent of CCS. In our studies of S. cerevisiae Sod1p, we noted a posttranslational modification to the inactive enzyme during hypoxia. Analysis of this modification by mass spectrometry revealed phosphorylation at serine 38. Serine 38 represents a putative proline-directed kinase target site located on a solvent-exposed loop that is positioned at one end of the Sod1p beta-barrel, a region immediately adjacent to residues previously shown to influence CCS-dependent activation. Although phosphorylation of serine 38 is minimal when the Sod1p is abundantly active (e.g., high oxygen level), up to 50% of Sod1p can be phosphorylated when CCS activation of the enzyme is blocked, e.g., by hypoxia or low-copper conditions. Serine 38 phosphorylation can be a marker for inactive pools of Sod1p. C1 [Leitch, Jeffry M.; Li, Cissy X.; Baron, J. Allen; Matthews, Lauren M.; Culotta, Valeria C.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA. [Cao, Xiaohang; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Hart, P. John] S Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Culotta, VC (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA. EM vculotta@jhsph.edu FU Johns Hopkins University National Institute of Environmental Health Sciences Center, National Institutes of Health (NIH) [GM 50016, NS 39112]; NIH [F32 GM 087904, ES 07141, T32 CA009110]; Judith and Jean Pape Adams Charitable Foundation FX This work was supported by the Johns Hopkins University National Institute of Environmental Health Sciences Center, National Institutes of Health (NIH) Grants GM 50016 (V.C.C.) and NS 39112 (P.J.H.), NIH Postdoctoral Fellowship F32 GM 087904 (J.M.L.), and NIH Training Grants ES 07141 (C.X.L.) and T32 CA009110 X.C. was supported in part by a grant by the Judith and Jean Pape Adams Charitable Foundation. NR 42 TC 7 Z9 7 U1 0 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 17 PY 2012 VL 51 IS 2 BP 677 EP 685 DI 10.1021/bi201353y PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876VJ UT WOS:000299135500011 PM 22148750 ER PT J AU Quante, M Bhagat, G Abrams, JA Marache, F Good, P Lee, MD Lee, Y Friedman, R Asfaha, S Dubeykovskaya, Z Mahmood, U Figueiredo, JL Kitajewski, J Shawber, C Lightdale, CJ Rustgi, AK Wang, TC AF Quante, Michael Bhagat, Govind Abrams, Julian A. Marache, Frederic Good, Pamela Lee, Michele D. Lee, Yoomi Friedman, Richard Asfaha, Samuel Dubeykovskaya, Zinaida Mahmood, Umar Figueiredo, Jose-Luiz Kitajewski, Jan Shawber, Carrie Lightdale, Charles J. Rustgi, Anil K. Wang, Timothy C. TI Bile Acid and Inflammation Activate Gastric Cardia Stem Cells in a Mouse Model of Barrett-Like Metaplasia SO CANCER CELL LA English DT Article ID DYSPLASIA-ADENOCARCINOMA SEQUENCE; GASTROESOPHAGEAL-REFLUX DISEASE; INTESTINAL METAPLASIA; TRANSGENIC MICE; SQUAMOUS EPITHELIUM; OXIDATIVE STRESS; DNA-DAMAGE; ESOPHAGUS; EXPRESSION; CANCER AB Esophageal adenocarcinoma (EAC) arises from Barrett esophagus (BE), intestinal-like columnar metaplasia linked to reflux esophagitis. In a transgenic mouse model of BE, esophageal overexpression of interleukin-1 beta phenocopies human pathology with evolution of esophagitis, Barrett-like metaplasia and EAC. Histopathology and gene signatures closely resembled human BE, with upregulation of TFF2, Bmp4, Cdx2, Notch1, and IL-6. The development of BE and EAC was accelerated by exposure to bile acids and/or nitrosamines, and inhibited by IL-6 deficiency. Lgr5(+) gastric cardia stem cells present in BE were able to lineage trace the early BE lesion. Our data suggest that BE and EAC arise from gastric progenitors due to a tumor-promoting IL-1 beta-IL-6 signaling cascade and DII1-dependent Notch signaling. C1 [Quante, Michael; Abrams, Julian A.; Marache, Frederic; Good, Pamela; Lee, Michele D.; Asfaha, Samuel; Dubeykovskaya, Zinaida; Lightdale, Charles J.; Wang, Timothy C.] Columbia Univ, Dept Med, Med Ctr, Div Digest & Liver Dis, New York, NY 10032 USA. [Quante, Michael; Bhagat, Govind; Abrams, Julian A.; Marache, Frederic; Good, Pamela; Lee, Michele D.; Asfaha, Samuel; Dubeykovskaya, Zinaida; Kitajewski, Jan; Shawber, Carrie; Lightdale, Charles J.; Wang, Timothy C.] Columbia Univ, Dept Med, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Bhagat, Govind] Columbia Univ, Dept Med, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Lee, Yoomi] Columbia Univ, Dept Med, Med Ctr, Div Hematol & Oncol, New York, NY 10032 USA. [Friedman, Richard] Columbia Univ, Dept Biomed Informat, Med Ctr, New York, NY 10032 USA. [Kitajewski, Jan; Shawber, Carrie] Columbia Univ, Dept Pathol Obstet & Gynecol, Med Ctr, New York, NY 10032 USA. [Mahmood, Umar] Harvard Univ, Sch Med, Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Figueiredo, Jose-Luiz] Harvard Univ, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Figueiredo, Jose-Luiz] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rustgi, Anil K.] Univ Penn, Div Gastroenterol, Dept Med & Genet, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Quante, Michael] Tech Univ Munich, Med Klin, Klinikum Rechts Isar, D-81675 Munich, Germany. RP Quante, M (reprint author), Columbia Univ, Dept Med, Med Ctr, Div Digest & Liver Dis, New York, NY 10032 USA. EM michael.quante@lrz.tum.de; tcw21@columbia.edu RI Asfaha, Samuel/I-8245-2015; OI Asfaha, Samuel/0000-0001-6972-0338; Bhagat, Govind/0000-0001-6250-048X FU NIH [RO1DK060758, 1U54CA126513, R01CA120979, 5U01 CA143056, P01-CA098101, P30-DK050306]; Mildred-Scheel-Stiftung, Deutsche Krebshilfe, Germany; NCI [K07 CA132892]; Louis V. Gerstner, Jr. Scholars Award FX These studies are supported by NIH (RO1DK060758, 1U54CA126513, and R01CA120979 to T.C.W; 5U01 CA143056 to A.K.R., T.C.W., U.M.). A.K.R. was further supported by NIH P01-CA098101 and P30-DK050306 grants. M.Q. was supported by a grant from the Mildred-Scheel-Stiftung, Deutsche Krebshilfe, Germany. J.A. is supported by a Career Development Award from the NCI (K07 CA132892) and by a Louis V. Gerstner, Jr. Scholars Award. We acknowledge the assistance of the Transgenic Mouse and Genomics Core of the Irving Cancer Research Center at Columbia University, and the Electronic Microscopy Core Facility at the University of Pennsylvania. We thank all members of the Wang lab for fruitful discussions. NR 68 TC 137 Z9 142 U1 3 U2 24 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN 17 PY 2012 VL 21 IS 1 BP 36 EP 51 DI 10.1016/j.ccr.2011.12.004 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 879XA UT WOS:000299365000007 PM 22264787 ER PT J AU Sabatine, MS Morrow, DA de Lemos, JA Omland, T Sloan, S Jarolim, P Solomon, SD Pfeffer, MA Braunwald, E AF Sabatine, Marc S. Morrow, David A. de Lemos, James A. Omland, Torbjorn Sloan, Sarah Jarolim, Petr Solomon, Scott D. Pfeffer, Marc A. Braunwald, Eugene TI Evaluation of Multiple Biomarkers of Cardiovascular Stress for Risk Prediction and Guiding Medical Therapy in Patients With Stable Coronary Disease SO CIRCULATION LA English DT Article DE angiotensin-converting enzyme inhibitors; biomarkers; coronary disease ID CHRONIC HEART-FAILURE; LEFT-VENTRICULAR DYSFUNCTION; ARTERY-DISEASE; NATRIURETIC PEPTIDE; IMMUNOLUMINOMETRIC ASSAY; PROGNOSTIC VALUE; RANDOMIZED-TRIALS; HUMAN PLASMA; ADRENOMEDULLIN; PRECURSOR AB Background-Circulating biomarkers can offer insight into subclinical cardiovascular stress and thus have the potential to aid in risk stratification and tailoring of therapy. Methods and Results-We measured plasma levels of 4 cardiovascular biomarkers, midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and copeptin, in 3717 patients with stable coronary artery disease and preserved left ventricular ejection fraction who were randomized to trandolapril or placebo as part of the Prevention of Events With Angiotensin Converting Enzyme (PEACE) trial. After adjustment for clinical cardiovascular risk predictors and left ventricular ejection fraction, elevated levels of MR-proANP, MR-proADM, and CT-proET-1 were independently associated with the risk of cardiovascular death or heart failure (hazard ratios per 1-SD increase in log-transformed biomarker levels of 1.97, 1.48, and 1.47, respectively; P <= 0.002 for each biomarker). These 3 biomarkers also significantly improved metrics of discrimination when added to a clinical model. Trandolapril significantly reduced the risk of cardiovascular death or heart failure in patients who had elevated levels of >= 2 biomarkers (hazard ratio, 0.53; 95% confidence interval, 0.36-0.80), whereas there was no benefit in patients with elevated levels of 0 or 1 biomarker (hazard ratio, 1.09; 95% confidence interval, 0.74-1.59; P(interaction) = 0.012). Conclusions-In patients with stable coronary artery disease and preserved left ventricular ejection fraction, our results suggest that elevated levels of novel biomarkers of cardiovascular stress may help identify patients who are at higher risk of cardiovascular death and heart failure and may be useful to select patients who derive significant benefit from angiotensin-converting enzyme inhibitor therapy. (Circulation. 2012;125:233-240.) C1 [Sabatine, Marc S.; Morrow, David A.; Sloan, Sarah; Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Sabatine, Marc S.; Morrow, David A.; Sloan, Sarah; Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [de Lemos, James A.] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA. [Omland, Torbjorn] Univ Oslo, Akershus Univ Hosp, Div Med, Oslo, Norway. [Omland, Torbjorn] Univ Oslo, Ctr Heart Failure Res, Oslo, Norway. [Omland, Torbjorn] Univ Oslo, KG Jebsen Cardiac Res Ctr, Oslo, Norway. [Jarolim, Petr] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Solomon, Scott D.; Pfeffer, Marc A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM msabatine@partners.org RI Solomon, Scott/I-5789-2013 FU National Heart, Lung, and Blood Institute (NHLBI) [N01 HC65149, R01 HL094390]; Knoll Pharmaceuticals; Abbott Laboratories; Accumetrics; Amgen; AstraZeneca; Beckman Coulter; BG Medicine; B. R. A. H. M. S. GmbH; Bristol-Myers Squibb; CV Therapeutics; Daiichi Sankyo Co Ltd; diaDexus; Eli Lilly and Co; Genentech; GlaxoSmithKline; Integrated Therapeutics; Johnson Johnson; Merck and Co; Nanosphere; Novartis Pharmaceuticals; Nuvelo; Ortho-Clinical Diagnostics; Pfizer; Roche Diagnostics; Sanofi-aventis; Siemens; Singulex; Roche; Alere, Inc; Alere; Johnson & Johnson Roche Diagnostics; Tethys Biomedical; Beckman-Coulter; Ortho Clinical Diagnostics; Siemens Healthcare Diagnostics; T2 Biosystems; Novartis; Anthera; Boehringer Ingelheim; Boston Scientific; Cerenis; Eleven Biotherapeutics; Hamilton Health Sciences; Karo Bio; Salutria; Sanofi Aventis; Servier; University of Oxford FX The PEACE trial was supported by a contract from the National Heart, Lung, and Blood Institute (NHLBI; N01 HC65149) and by Knoll Pharmaceuticals and Abbott Laboratories, which also provided the study medication. Dr Sabatine was supported in part by grant R01 HL094390 from the NHLBI. Reagent for measurement of MR-proANP, MR-proADM, CT-proET-1, and copeptin were provided by B. R. A. H. M. S. GmbH (Henningsdorf, Germany). The NHLBI, Knoll Pharmaceuticals, Abbott Laboratories, and B. R. A. H. M. S. GmbH had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.; Drs Sabatine, Morrow, and Braunwald and S. Sloan are members of the TIMI Study Group, which has received research grant support from Accumetrics, Amgen, AstraZeneca, Beckman Coulter, BG Medicine, B. R. A. H. M. S. GmbH, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo Co Ltd, diaDexus, Eli Lilly and Co, Genentech, GlaxoSmithKline, Integrated Therapeutics, Johnson & Johnson, Merck and Co, Nanosphere, Novartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-aventis, Siemens, and Singulex. Dr Sabatine reports receiving honoraria for educational presentations from Bristol-Myers Squibb and diaDexus, as well as remuneration for consulting from AstraZeneca, Bristol-Myers Squibb/Sanofi-aventis Joint Venture, Daiichi-Sankyo/Lilly Partnership, Sanofi-aventis, and Singulex. Dr Morrow reports receiving honoraria for educational presentations from Eli Lilly; remuneration for consulting from Beckman-Coulter, Boehringer Ingelheim, Cardiokinetix, Critical Diagnostics, Gilead, Instrumentation Laboratory, Ikaria, Menarini, Merck, OrthoClinical Diagnostics, Servier, Roche Diagnostics, and Siemens; and remuneration from AstraZeneca for adjudication as a member of a Clinical Events Committee. Dr de Lemos reports receiving grant support from Roche and Alere, Inc (formerly Biosite) and consulting income from Alere, Johnson & Johnson Roche Diagnostics, and Tethys Biomedical. Dr Omland reports receiving speakers' honoraria from Roche Diagnostics and Abbott Laboratories. Dr Jarolim reports receiving research support from Amgen, Beckman-Coulter, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics; honoraria for educational presentations from Ortho Clinical Diagnostics; and consulting fees from T2 Biosystems. Dr Pfeffer reports receiving grant support from Amgen, Novartis, and Sanofi-aventis, as well as consulting fees from Amgen, Anthera, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cerenis, Eleven Biotherapeutics, GlaxoSmithKline, Hamilton Health Sciences, Karo Bio, Novartis, Roche, Salutria, Sanofi Aventis, Servier, and University of Oxford. Dr Pfeffer is a coinventor on a patent that Brigham and Women's Hospital has for the use of inhibitors of the renin-angiotensin system in selected survivors of MI. His share of the licensing agreements with Novartis and Boehringer, which are irrevocably transferred to charity, are not linked to sales. Dr Braunwald reports receiving remuneration for symposia and/or consulting from Amorcyte, CardioRentis, CVRx, Daiichi Sankyo, Eli Lilly, Genzyme, Medicines Co, and Merck & Co. The other authors report no conflicts. NR 36 TC 61 Z9 64 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 17 PY 2012 VL 125 IS 2 BP 233 EP U137 DI 10.1161/CIRCULATIONAHA.111.063842 PG 25 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 879HZ UT WOS:000299321600012 PM 22179538 ER EF