FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Young, J Zhang, M Tavora, F Oliveira, JB Burke, A AF Young, J. Zhang, M. Tavora, F. Oliveira, J. B. Burke, A. TI DSG2 Mutations in ARVC: A Molecular Autopsy 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 Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. Fudan Univ, Shanghai Med Coll, Shanghai 200433, Peoples R China. NIH, Bethesda, MD 20892 USA. Messejana Heart & Lung Hosp, Fortaleza, Ceara, Brazil. 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 17 BP 7A EP 7A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986900018 ER PT J AU Siddiqui, SW Dunleavy, K Arthur, DC Filie, AC AF Siddiqui, S. W. Dunleavy, K. Arthur, D. C. Filie, A. C. TI Utility of Fine Needle Aspiration for c-MYC Interphase Fluorescence In-Situ Hybridization Analysis of Aggressive B-Cell Lymphomas 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 [Siddiqui, S. W.; Dunleavy, K.; Arthur, D. C.; Filie, A. C.] NCI, Bethesda, MD 20892 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 432 BP 106A EP 106A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986900433 ER PT J AU Hudson, J Duncavage, E Wells, S Tamburrino, A Salerno, P Xi, L Raffeld, M Moley, J Chernock, R AF Hudson, J. Duncavage, E. Wells, S. Tamburrino, A. Salerno, P. Xi, L. Raffeld, M. Moley, J. Chernock, R. TI Characterization of microRNA Expression in Medullary Thyroid Carcinoma 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 Washington Univ, Sch Med, St Louis, MO USA. NCI, Bethesda, MD 20892 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 600 BP 146A EP 146A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986900601 ER PT J AU Jung, CK Lubin, JH Brenner, AV Little, MP Sigurdson, AJ Nikiforov, YE AF Jung, C. K. Lubin, J. H. Brenner, A. V. Little, M. P. Sigurdson, A. J. Nikiforov, Y. E. TI The Increase in Papillary Thyroid Cancer Incidence in the US during the Last Four Decades Is Accompanied by a High and Stable Frequency of BRAF Mutations and a Sharp Increase in NRAS Mutations 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 Pittsburgh, Pittsburgh, PA USA. Catholic Univ Korea, Seoul, South Korea. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 602 BP 146A EP 146A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986900603 ER PT J AU Shuch, B Linehan, M Merino, MJ AF Shuch, B. Linehan, M. Merino, M. J. TI Are Adrenal Lesions Part of the Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome (HLRCC)? 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 [Shuch, B.; Linehan, M.; Merino, M. J.] NCI, Bethesda, MD 20892 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 621 BP 150A EP 150A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986900622 ER PT J AU Walter, BA Barak, S Fojo, A Merino, MJ AF Walter, B. A. Barak, S. Fojo, A. Merino, M. J. TI The Role of MicroRNA Expression in the Diagnosis of Adrenocortical Carcinomas. A Marker of Poor Prognostic Tumors 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 [Walter, B. A.; Barak, S.; Fojo, A.; Merino, M. J.] NCI, NIH, Bethesda, MD 20892 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 626 BP 151A EP 151A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986900627 ER PT J AU Lai, JP Aung, PP Khangura, S Kamal, N Gallin, JI Holland, SM Malech, HL Heller, T Quezado, M AF Lai, J-P Aung, P. P. Khangura, S. Kamal, N. Gallin, J. I. Holland, S. M. Malech, H. L. Heller, T. Quezado, M. TI Chronic Granulomatous Disease Involving Gastrointestinal Tract (Pathology Study of 87 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 [Lai, J-P; Aung, P. P.; Khangura, S.; Kamal, N.; Gallin, J. I.; Holland, S. M.; Malech, H. L.; Heller, T.; Quezado, M.] NCI, NIH, Bethesda, MD 20892 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 690 BP 166A EP 166A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986900691 ER PT J AU Aung, PP Linehan, WM Poropatich, CO Merino, MJ AF Aung, P. P. Linehan, W. M. Poropatich, C. O. Merino, M. J. TI Primary Neuroendocrine Tumors of the Kidney. Morphological and Molecular Alterations of an Uncommon Malignancy 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, NIH, Bethesda, MD 20892 USA. Virginia Hosp Ctr, Arlington, VA 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 792 BP 191A EP 191A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901069 ER PT J AU Hipp, JD Monaco, J Kunju, PL Cheng, J Yagi, Y Rodriguez-Canales, J Emmert-Buck, MR Hewitt, S Feldman, MD Tomaszewski, JE Toner, M Tompkins, RG Flotte, T Lucas, D Gilbertson, JR Madabhushi, A Balis, UJ AF Hipp, J. D. Monaco, J. Kunju, P. L. Cheng, J. Yagi, Y. Rodriguez-Canales, J. Emmert-Buck, M. R. Hewitt, S. Feldman, M. D. Tomaszewski, J. E. Toner, M. Tompkins, R. G. Flotte, T. Lucas, D. Gilbertson, J. R. Madabhushi, A. Balis, U. J. TI Integration of Architectural and Cytologic Driven Image Algorithms for Prostate Adenocarcinoma Identification 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 Univ Michigan, Ann Arbor, MI 48109 USA. Rutgers State Univ, Piscataway, NJ USA. Harvard, Boston, MA USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Penn, Perlman Sch Med, Philadelphia, PA 19104 USA. Mayo Clin, Rochester, MN 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 890 BP 213A EP 214A PG 2 WC Pathology SC Pathology GA 888EP UT WOS:000299986901167 ER PT J AU Jin-Ping, L Rodriguez, BAW Aung, PP Linehan, M Merino, MJ AF Jin-Ping, L. Rodriguez, B. A. Walter Aung, P. P. Linehan, M. Merino, M. J. TI Mixed Epithelial and Stromal Tumor of Kidney, Molecular and IHC Findings of a Possible New Hereditary Syndrome 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 [Jin-Ping, L.; Rodriguez, B. A. Walter; Aung, P. P.; Linehan, M.; Merino, M. J.] NCI, NIH, Bethesda, MD 20892 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 899 BP 215A EP 216A PG 2 WC Pathology SC Pathology GA 888EP UT WOS:000299986901176 ER PT J AU Navaei, AH Aung, PP Walter, BA Pinto, P Merino, MJ AF Navaei, A. H. Aung, P. P. Walter, B. A. Pinto, P. Merino, M. J. TI Correlation between ERG Fusion Protein and Androgen Receptor Expression in Prostate Cancer; Possible Role in Diagnosis and Therapy 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 [Navaei, A. H.; Aung, P. P.; Walter, B. A.; Pinto, P.; Merino, M. J.] NCI, NIH, Bethesda, MD 20892 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 963 BP 230A EP 230A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901240 ER PT J AU Biancotto, A Dagur, PK Fuchs, JC Wiestner, A Bagwell, CB Mccoy, JP AF Biancotto, Angelique Dagur, Pradeep K. Fuchs, John C. Wiestner, Adrian Bagwell, C. Bruce McCoy, J. Philip, Jr. TI Phenotypic complexity of T regulatory subsets in patients with B-chronic lymphocytic leukemia SO MODERN PATHOLOGY LA English DT Article DE chronic lymphocytic leukemia; immunophenotyping; T-reg ID CD38 EXPRESSION; SUPPRESSIVE FUNCTION; CELL RESPONSES; EXPANSION; FREQUENCY; ZAP-70; CD4; DIFFERENTIATION; INTERLEUKIN-7; SURVIVAL AB Increased numbers of T regulatory (T-reg) cells are found in B-chronic lymphocytic leukemia, but the nature and function of these T-regs remains unclear. Detailed characterization of the T-regs in chronic lymphocytic leukemia has not been performed and the degree of heterogeneity of among these cells has not been studied to date. Using 15-color flow cytometry we show that T-reg, cells, defined using CD4, CD25, and forkhead box P3 (FOXP3), can be divided into multiple complex subsets based on markers used for naive, memory, and effector delineation as well as markers of T-reg activation. Furthermore FOXP3 cells can be identified among CD4(+)CD25(-) as well as CD8(+)CD4(-) populations in increased proportions in patients with chronic lymphocytic leukemia compared with healthy donors. Significantly different frequencies of naive and effector T-regs populations are found in healthy donor controls compared with donors with chronic lymphocytic leukemia. A population of CCR7(+)CD39(+) T-regs was significantly associated with chronic lymphocytic leukemia. This population demonstrated slightly reduced suppressive activity compared with total T-regs Or T-regs of healthy donors. These data suggest that FOXP3-expressing cells, particularly in patients with chronic lymphocytic leukemia are much more complex for T-reg sub-populations and transitions than previously reported. These findings demonstrate the complexity of regulation of T-cell responses in chronic lymphocytic leukemia and illustrate the use of high-dimensional analysis of cellular phenotypes in facilitating understanding of the intricacies of cellular immune responses and their dysregulation in cancer. Modern Pathology (2012) 25, 246-259; doi:10.1038/modpathol.2011.164; published online 18 November 2011 C1 [McCoy, J. Philip, Jr.] NHLBI, Ctr Human Immunol Autoimmun & Inflammat, NIH, Bethesda, MD 20892 USA. [Dagur, Pradeep K.; McCoy, J. Philip, Jr.] NHLBI, Flow Cytometiy Core Lab, Bethesda, MD 20892 USA. [Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Bagwell, C. Bruce] Ver Software House, Topsham, ME USA. RP Mccoy, JP (reprint author), NHLBI, Ctr Human Immunol Autoimmun & Inflammat, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM mccoyjp@mail.nih.gov FU NHLBI; CHI, NIH, Bethesda, MD, USA FX We are grateful to Dr. M. Roederer and Dr. P. Chattopadhyay for their generous assistance. This research was supported by the Intramural Research Program of the NHLBI and by the CHI, NIH, Bethesda, MD, USA. NR 49 TC 10 Z9 11 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 IS 2 BP 246 EP 259 DI 10.1038/modpathol.2011.164 PG 14 WC Pathology SC Pathology GA 888EK UT WOS:000299986400010 PM 22101351 ER PT J AU Romero, VAV Rodriguez, BAW Merino, MJ AF Romero, V. A. Valera Rodriguez, B. A. Walter Merino, M. J. TI Molecular Classification Helps Discriminate between Oncocytomas and Chromophobe Renal Carcinomas Using Meta-Analysis of Gene Expression Microarrays 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 [Romero, V. A. Valera; Rodriguez, B. A. Walter; Merino, M. J.] NCI, NIH, Bethesda, MD 20892 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 1039 BP 247A EP 247A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901316 ER PT J AU Rodriguez, BAW Romero, VAV Linehan, M Merino, MJ AF Rodriguez, B. A. Walter Romero, V. A. Valera Linehan, M. Merino, M. J. TI Mitochondria Respiratory Chain Gene Expression Analysis in Renal Cell Carcinoma 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 NIN, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 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 1047 BP 249A EP 249A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901324 ER PT J AU Walter, BA Valera, VA Pacak, K Linehan, M Merino, MJ AF Walter, B. A. Valera, V. A. Pacak, K. Linehan, M. Merino, M. J. TI How Immunohistochemistry Can Help To Identify Renal Tumors Associated with SDHB Syndrome 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 [Walter, B. A.; Valera, V. A.; Pacak, K.; Linehan, M.; Merino, M. J.] NCI, NIH, Bethesda, MD 20892 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 1046 BP 249A EP 249A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901323 ER PT J AU Davidson, B Abeler, V Hellesylt, E Holth, A Shih, IM Kristensen, GB Skeie-Jensen, T Yang, Y Wang, TL AF Davidson, B. Abeler, V. Hellesylt, E. Holth, A. Shih, I-M Kristensen, G. B. Skeie-Jensen, T. Yang, Y. Wang, T-L TI Gene Expression Signatures Differentiate Uterine Leiomyosarcoma and 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 Norwegian Radium Hosp, Oslo, Norway. Johns Hopkins Med Inst, Baltimore, MD USA. NIH, Bethesda, MD 20892 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 1112 BP 265A EP 265A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901389 ER PT J AU Gomez-Macias, GS Stratton, P Rodriguez, BAW Merino, MJ AF Gomez-Macias, G. S. Stratton, P. Rodriguez, B. A. Walter Merino, M. J. TI Does GVHD Involve the Gyn Tract? Immunohistochemical Expression of Elafin as a Marker of Graft-Versus-Host Disease in Gynecological Biopsies 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, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 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 1142 BP 272A EP 273A PG 2 WC Pathology SC Pathology GA 888EP UT WOS:000299986901419 ER PT J AU Bajor-Dattilo, EB Leung, A Dunleavy, K Pack, S Arthur, D Raffeld, M Wilson, W Jaffe, ES Pittaluga, S AF Bajor-Dattilo, E. B. Leung, A. Dunleavy, K. Pack, S. Arthur, D. Raffeld, M. Wilson, W. Jaffe, E. S. Pittaluga, S. TI Correlation of MYC Gene Translocation Status with MYC Protein Expression in Burkitt Lymphoma and Diffuse Large B 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 [Bajor-Dattilo, E. B.; Leung, A.; Dunleavy, K.; Pack, S.; Arthur, D.; Raffeld, M.; Wilson, W.; Jaffe, E. S.; Pittaluga, S.] NIH, Bethesda, MD 20892 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 \1359 BP 324A EP 324A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901636 ER PT J AU Calvo, KR Corrigan-Cummins, M Costello, R Tembhare, P Yuan, CM Stetler-Stevenson, M Korde, N Kwok, M Yancey, MA Mulquin, M Simakova, O Adriana, Z Landgren, O Maric, I AF Calvo, K. R. Corrigan-Cummins, M. Costello, R. Tembhare, P. Yuan, C. M. Stetler-Stevenson, M. Korde, N. Kwok, M. Yancey, M. A. Mulquin, M. Simakova, O. Adriana, Z. Landgren, O. Maric, I. TI Immunophenotypic Profiles of Plasma Cells in Myeloma Precursor Disease Correlate with the Extent of Disease and Risks for Progression 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 CC, Bethesda, MD USA. NCI, Bethesda, MD 20892 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 1368 BP 326A EP 326A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901645 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 Climent, F Pittaluga, S Martinez, D Gonzalez-Barca, E Romagosa, V Raffeld, M Campo, E Jaffe, ES AF Climent, F. Pittaluga, S. Martinez, D. Gonzalez-Barca, E. Romagosa, V. Raffeld, M. Campo, E. Jaffe, E. S. TI Clinicopathologic Study of Mature T-Cell Lymphoma with B-Cell Markers: A Review of 21 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 Bellvitge Hosp, Barcelona, Spain. NCI, NIH, Bethesda, MD 20892 USA. Hosp Clin Barcelona, Barcelona, Spain. Inst Catala Oncol, Barcelona, Spain. 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 1384 BP 330A EP 330A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901661 ER PT J AU Huppmann, AR Pittaluga, S Raffeld, M Xi, L Jaffe, ES AF Huppmann, A. R. Pittaluga, S. Raffeld, M. Xi, L. Jaffe, E. S. TI Subcutaneous Panniculitis-Like T-Cell Lymphoma in Children 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 [Huppmann, A. R.; Pittaluga, S.; Raffeld, M.; Xi, L.; Jaffe, E. S.] NCI, NIH, Bethesda, MD 20892 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 1433 BP 342A EP 342A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901710 ER PT J AU Liu, Q Davies-Hill, T Pakzad, K Raffeld, M Xi, L Pittaluga, S Jaffe, ES AF Liu, Q. Davies-Hill, T. Pakzad, K. Raffeld, M. Xi, L. Pittaluga, S. Jaffe, E. S. TI Increased CD5 Positive Polyclonal B-Cells in Castleman Disease, and Lymphoid Hyperplasia with Castleman-Like Features: A Diagnostic Pitfall 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 [Liu, Q.; Davies-Hill, T.; Pakzad, K.; Raffeld, M.; Xi, L.; Pittaluga, S.; Jaffe, E. S.] NCI, NIH, Bethesda, MD 20892 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 1478 BP 352A EP 352A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901755 ER PT J AU Maric, I Liu, QY Korde, N Simakova, O Calvo, K Zingone, A Costello, R Yancey, MA Tembhare, P Yuan, C Stetler-Stevenson, M Landgren, O AF Maric, I. Liu, Q. Y. Korde, N. Simakova, O. Calvo, K. Zingone, A. Costello, R. Yancey, M. A. Tembhare, P. Yuan, C. Stetler-Stevenson, M. Landgren, O. TI Mature Megakaryocytes Display High-Level CD34 Expression in a Subset of Patients with Myeloma Precursor 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 NIH, CC, Bethesda, MD 20892 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 1488 BP 354A EP 354A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986901765 ER PT J AU Menon, MP Jegalion, A Raffeld, M Pittaluga, S Xi, L Jaffe, ES AF Menon, M. P. Jegalion, A. Raffeld, M. Pittaluga, S. Xi, L. Jaffe, E. S. TI Primary CNS T-Cell Lymphomas: Clinical, Morphologic, Immunophenotypic and Molecular Analysis 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, NIH, Bethesda, MD 20892 USA. Cleveland Clin, Cleveland, OH 44106 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 1491 BP 355A EP 355A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902003 ER PT J AU Simakova, O Wilson, T Wang, M Olivares, N Klion, A Metcalfe, DD Maric, I AF Simakova, O. Wilson, T. Wang, M. Olivares, N. Klion, A. Metcalfe, D. D. Maric, I. TI Differential Expression of Activation-Related Antigens on Masts Cells and Eosinophils in Patients with Systemic Mastocytosis and Hypereosinophilic Syndrome 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 NIH, CC, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 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 1548 BP 369A EP 370A PG 2 WC Pathology SC Pathology GA 888EP UT WOS:000299986902060 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 Valera, A Colomo, L Martinez, A de Jong, D Balague, O Matheu, G Martinez, M Taddesse-Heath, L Jaffe, ES Bacchi, CE Campo, E AF Valera, A. Colomo, L. Martinez, A. de Jong, D. Balague, O. Matheu, G. Martinez, M. Taddesse-Heath, L. Jaffe, E. S. Bacchi, C. E. Campo, E. TI ALK Positive Large B-Cell Lymphomas (ALK plus LBCL) Express the Terminal Plasma Cell Differentiation Program but Lack MYC Rearrangements 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 Hosp Clin Barcelona, Barcelona, Spain. Netherlands Canc Inst, Amsterdam, Netherlands. Hosp Manacor, Manacor, Spain. Lab Hematopatol, Mendoza, Argentina. Howard Univ Hosp, Washington, DC USA. NCI, Bethesda, MD 20892 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 1578 BP 377A EP 377A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902090 ER PT J AU Yang, HC Morden, A Pastan, I Matsusaka, T Ichikawa, I Fogo, AB AF Yang, H-C Morden, A. Pastan, I. Matsusaka, T. Ichikawa, I. Fogo, A. B. TI Absence of PAI-1 Results in Direct Podocyte Protection In Vivo 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 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Florida State Univ, Tallahassee, FL 32306 USA. NCI, Bethesda, MD 20892 USA. Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. 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 1710 BP 409A EP 409A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902222 ER PT J AU Guy, CD Brunt, EM Behling, C Torbenson, M Yeh, MM Belt, P Neuschwander-Tetri, BA Murray, KF Kleiner, DE AF Guy, C. D. Brunt, E. M. Behling, C. Torbenson, M. Yeh, M. M. Belt, P. Neuschwander-Tetri, B. A. Murray, K. F. Kleiner, D. E. TI Hepatic Glycogenosis in Children with Nonalcoholic Fatty Liver Disease (NAFLD): A Different Disease Than Glycogenic Hepatopathy 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 Duke Univ, Durham, NC USA. Washington Univ, St Louis, MO USA. Sharp Hosp, San Diego, CA USA. Johns Hopkins Sch Med, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. St Louis Univ, Sch Med, St Louis, MO USA. Seattle Childrens Hosp, Seattle, WA USA. NIH, Bethesda, MD 20892 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 1728 BP 414A EP 414A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902240 ER PT J AU Kleiner, DE Behling, C Guy, CD Torbenson, M Yeh, MM Belt, P Neuschwander-Tetri, BA Brunt, EM AF Kleiner, D. E. Behling, C. Guy, C. D. Torbenson, M. Yeh, M. M. Belt, P. Neuschwander-Tetri, B. A. Brunt, E. M. TI Glycogenosis Is Associated with Measures of Insulin Resistance in Adults with Non-Alcoholic Fatty Liver Disease (NAFLD) 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. Sharp Hosp, San Diego, CA USA. Duke Univ, Durham, NC USA. Johns Hopkins Sch Med, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. St Louis Univ, St Louis, MO 63103 USA. Washington Univ, St Louis, MO 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 1737 BP 416A EP 416A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902249 ER PT J AU Lai, JP Aung, PP Wang, Z Rosenberg, A Kleiner, D Roberts, LR Miettinen, M AF Lai, J-P Aung, P. P. Wang, Z. Rosenberg, A. Kleiner, D. Roberts, L. R. Miettinen, M. TI Oncogenic SULF2 Protein Expression Is Associated with Pathogenesis of Cirrhosis and Hepatobiliary Carcinoma 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, NIH, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN 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 1742 BP 417A EP 417A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902254 ER PT J AU Nobrega, R Patrocinio, R Aung, PP Lai, JP Wang, Z Miettinen, M Warren, K Quezado, M AF Nobrega, R. Patrocinio, R. Aung, P. P. Lai, J-P Wang, Z. Miettinen, M. Warren, K. Quezado, M. TI Expression Status of IDH1 Mutant and SDHB Genes in Adult and Pediatric Gliomas 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, NIH, Bethesda, MD 20892 USA. BIOPSE Lab, Fortaleza, Ceara, Brazil. Fac Med Christus, Fortaleza, Ceara, Brazil. 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 1806 BP 433A EP 433A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902318 ER PT J AU Arora, K Zhang, W Fukuoka, J Kitano, H Jagirdar, J AF Arora, K. Zhang, W. Fukuoka, J. Kitano, H. Jagirdar, J. TI Detection of EGFR Mutations in Lung Adenocarcinoma by Immunohistochemistry Using Mutant Specific Antibodies: Are We There Yet? 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 Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Toyama Univ, Toyama 930, Japan. NIH, Bethesda, MD 20892 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 1961 BP 471A EP 471A PG 1 WC Pathology SC Pathology GA 888EP UT WOS:000299986902473 ER PT J AU Cherkasova, V Maury, LL Bacikova, D Pridham, K Bahler, J Maraia, RJ AF Cherkasova, Vera Maury, Luis Lopez Bacikova, Dagmar Pridham, Kevin Baehler, Juerg Maraia, Richard J. TI Altered nuclear tRNA metabolism in La-deleted Schizosaccharomyces pombe is accompanied by a nutritional stress response involving Atf1p and Pcr1p that is suppressible by Xpo-t/Los1p SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID POLYMERASE-III TRANSCRIPTS; PRECURSOR TRANSFER-RNAS; MEIOTIC RECOMBINATION HOTSPOT; METHIONYL-TRANSFER-RNA; CELL-CYCLE CHECKPOINT; FISSION YEAST; SACCHAROMYCES-CEREVISIAE; NITROGEN STARVATION; GENE-EXPRESSION; GCN4 TRANSLATION AB Deletion of the sla1(+) gene, which encodes a homologue of the human RNA-binding protein La in Schizosaccharomyces pombe, causes irregularities in tRNA processing, with altered distribution of pre-tRNA intermediates. We show, using mRNA profiling, that cells lacking sla1(+) have increased mRNAs from amino acid metabolism (AAM) genes and, furthermore, exhibit slow growth in Edinburgh minimal medium. A subset of these AAM genes is under control of the AP-1-like, stress-responsive transcription factors Atf1p and Pcr1p. Although S. pombe growth is resistant to rapamycin, sla1-Delta cells are sensitive, consistent with deficiency of leucine uptake, hypersensitivity to NH4, and genetic links to the target of rapamycin (TOR) pathway. Considering that perturbed intranuclear pre-tRNA metabolism and apparent deficiency in tRNA nuclear export in sla1-Delta cells may trigger the AAM response, we show that modest overexpression of S. pombe los1(+) (also known as Xpo-t), encoding the nuclear exportin for tRNA, suppresses the reduction in pre-tRNA levels, AAM gene up-regulation, and slow growth of sla1-Delta cells. The conclusion that emerges is that sla1(+) regulates AAM mRNA production in S. pombe through its effects on nuclear tRNA processing and probably nuclear export. Finally, the results are discussed in the context of stress response programs in Saccharomyces cerevisiae. C1 [Cherkasova, Vera; Bacikova, Dagmar; Pridham, Kevin; Maraia, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. [Maury, Luis Lopez; Baehler, Juerg] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England. [Maury, Luis Lopez; Baehler, Juerg] UCL Canc Inst, London WC1E 6BT, England. [Maraia, Richard J.] US PHS, Rockville, MD 20852 USA. RP Maraia, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. EM maraiar@mail.nih.gov RI Bahler, Jurg/B-4572-2009; Lopez-Maury, Luis/B-3715-2015 OI Bahler, Jurg/0000-0003-4036-1532; Lopez-Maury, Luis/0000-0002-3510-0621 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We thank Shiv Grewal, Vincent Geli, and Henry Levin for strains and/or plasmids, Mike Cashel for advice on analysis of media components, Bob Intine for RNA preparation for one of the microarray experiments, Shelly Sazer for a los1-mutant allele used during an early phase of this work, Marty Blum for media preparation, Nate Blewett for discussion, and Alan Hinnebusch and anonymous reviewers for critical reading of an earlier version of the manuscript. This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 103 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD FEB 1 PY 2012 VL 23 IS 3 BP 480 EP 491 DI 10.1091/mbc.E11-08-0732 PG 12 WC Cell Biology SC Cell Biology GA 894EN UT WOS:000300409900007 PM 22160596 ER PT J AU Chen, M Shabashvili, D Nawab, A Yang, SX Dyer, LM Brown, KD Hollingshead, M Hunter, KW Kaye, FJ Hochwald, SN Marquez, VE Steeg, P Zajac-Kaye, M AF Chen, Min Shabashvili, Daniel Nawab, Akbar Yang, Sherry X. Dyer, Lisa M. Brown, Kevin D. Hollingshead, Melinda Hunter, Kent W. Kaye, Frederic J. Hochwald, Steven N. Marquez, Victor E. Steeg, Patricia Zajac-Kaye, Maria TI DNA Methyltransferase Inhibitor, Zebularine, Delays Tumor Growth and Induces Apoptosis in a Genetically Engineered Mouse Model of Breast Cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID FREQUENT EPIGENETIC INACTIVATION; P53-MEDIATED G(1) ARREST; CYCLIN D2 EXPRESSION; TRANSGENIC MICE; PROMOTER HYPERMETHYLATION; P53-DEPENDENT APOPTOSIS; EPITHELIAL-CELLS; MAMMARY-TUMORS; SFRP GENES; IN-VITRO AB Zebularine is a novel potent inhibitor of both cytidine deaminase and DNA methylation. We examined the effect of zebularine on mammary tumor growth in genetically engineered MMTV-PyMT transgenic mice that develop mammary tumors at 60 days of age with 100% penetrance. The MMTV-PyMT transgenic mice were randomized at 46 days of age into control (n = 25) and zebularine (n = 25) treatment groups and monitored for parameters of tumor growth. Zebularine was administered at 5 mg/mL in drinking water. We observed a significant delay in the growth of mammary tumors in zebularine-treated mice with a statistically significant reduction (P = 0.0135) in total tumor burden at 94 days of age when the mice were sacrificed. After 48 days of zebularine treatment, the tumors were predominantly necrotic compared with untreated animals. In addition, a high apoptotic index by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was observed as early as 13 days following treatment. Immunoblot analysis showed depletion of DNMT1 and partial depletion of DNMT3b after zebularine treatment. Microarray analyses of global gene expression identified upregulation of twelve methylation-regulated genes as well as a set of candidate cancer genes that participate in cell growth and apoptosis. In summary, zebularine inhibits the growth of spontaneous mammary tumors and causes early onset of tumor cell necrosis and apoptosis in a genetically engineered mouse model of breast cancer. Defining the parameters of zebularine-mediated tumor inhibition may advance the future development of DNA methyltransferase inhibitors as an effective cancer treatment. Mol Cancer Ther; 11(2); 370-82. (C) 2011 AACR. C1 [Zajac-Kaye, Maria] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL 32610 USA. [Chen, Min; Kaye, Frederic J.; Zajac-Kaye, Maria] Univ Florida, Dept Med, Gainesville, FL 32610 USA. [Dyer, Lisa M.; Brown, Kevin D.] Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. [Hochwald, Steven N.] Univ Florida, Dept Surg, Gainesville, FL 32610 USA. [Yang, Sherry X.] NCI Frederick, Natl Clin Target Validat Lab, Frederick, MD USA. [Hollingshead, Melinda] NCI Frederick, Dev Therapeut Program, Frederick, MD USA. [Hunter, Kent W.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Marquez, Victor E.] NCI, Med Chem Lab, Bethesda, MD 20892 USA. [Steeg, Patricia] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Zajac-Kaye, M (reprint author), Univ Florida, Coll Med, Dept Anat & Cell Biol, Canc & Genet Res Complex,Room 360,2033 Mowry Rd, Gainesville, FL 32610 USA. EM mzajackaye@ufl.edu FU National Cancer Institute; Department of Medicine at the University of Florida; Department of Anatomy and Cell Biology at the University of Florida FX This work was supported by National Cancer Institute intramural program and by the Department of Medicine and Department of Anatomy and Cell Biology at the University of Florida. NR 58 TC 19 Z9 19 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD FEB PY 2012 VL 11 IS 2 BP 370 EP 382 DI 10.1158/1535-7163.MCT-11-0458 PG 13 WC Oncology SC Oncology GA 894GO UT WOS:000300415300012 PM 22203734 ER PT J AU Buxton, DB AF Buxton, Denis B. TI The impact of nanotechnology on myocardial infarction treatment SO NANOMEDICINE LA English DT Editorial Material DE diagnostics; myocardial infarction; nanotechnology; regenerative medicine; therapeutic delivery ID SELF-ASSEMBLING PEPTIDES; DELIVERY; MONOCYTES; TISSUE; HEART AB "Nanotechnology has the potential to play a role in improving outcomes from MI at multiple points in the disease process. These include earlier and more sensitive diagnosis of developing MI, improved treatments of acute MI with drugs, cell therapy and siRNA, and tissue engineering approaches for preventing infarct expansion and the development of heart failure." RP Buxton, DB (reprint author), NHLBI, Basic & Early Translat Res Program, Div Cardiovasc Sci, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM db225a@nih.gov OI Buxton, Denis/0000-0003-3077-6435 NR 15 TC 3 Z9 3 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD FEB PY 2012 VL 7 IS 2 BP 173 EP 175 DI 10.2217/NNM.11.184 PG 3 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 893DM UT WOS:000300335800002 PM 22339129 ER PT J AU Trcek, T Chao, JA Larson, DR Park, HY Zenklusen, D Shenoy, SM Singer, RH AF Trcek, Tatjana Chao, Jeffrey A. Larson, Daniel R. Park, Hye Yoon Zenklusen, Daniel Shenoy, Shailesh M. Singer, Robert H. TI Single-mRNA counting using fluorescent in situ hybridization in budding yeast SO NATURE PROTOCOLS LA English DT Article ID ACTIN GENE-EXPRESSION; LABELED PROBES; LOCALIZATION; MOLECULES; VISUALIZATION; PROTEIN; CELLS; TRANSCRIPTION; COMPLEX AB Fluorescent in situ hybridization (FISH) allows the quantification of single mRNAs in budding yeast using fluorescently labeled single-stranded DNA probes, a wide-field epifluorescence microscope and a spot-detection algorithm. Fixed yeast cells are attached to coverslips and hybridized with a mixture of FISH probes, each conjugated to several fluorescent dyes. Images of cells are acquired in 3D and maximally projected for single-molecule analysis. Diffraction-limited labeled mRNAs are observed as bright fluorescent spots and can be quantified using a spot-detection algorithm. FISH preserves the spatial distribution of cellular RNA distribution within the cell and the stochastic fluctuations in individual cells that can lead to phenotypic differences within a clonal population. This information, however, is lost if the RNA content is measured on a population of cells by using reverse transcriptase PCR, microarrays or high-throughput sequencing. The FISH procedure and image acquisition described here can be completed in 3 d. C1 [Trcek, Tatjana; Chao, Jeffrey A.; Park, Hye Yoon; Shenoy, Shailesh M.; Singer, Robert H.] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10467 USA. [Larson, Daniel R.] NCI, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Zenklusen, Daniel] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. [Singer, Robert H.] Albert Einstein Coll Med, Gruss Lipper Biophoton Ctr, Bronx, NY 10467 USA. RP Singer, RH (reprint author), Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10467 USA. EM robert.singer@einstein.yu.edu RI Larson, Daniel/B-9829-2008; Zenklusen, Daniel/C-4503-2008; Park, Hye Yoon/N-9618-2014; OI Larson, Daniel/0000-0001-9253-3055; Zenklusen, Daniel/0000-0002-0067-0093; Park, Hye Yoon/0000-0003-4704-8178; Shenoy, Shailesh/0000-0002-5132-7236 FU US National Institutes of Health [GM57071, GM86217]; Canadian Institutes of Health Research FX We thank the Singer laboratory members for critical review of this manuscript. This work was supported by US National Institutes of Health grants GM57071 and GM86217 (awarded to R.H.S.) and a grant from the Canadian Institutes of Health Research (awarded to D.Z.) NR 35 TC 31 Z9 31 U1 1 U2 44 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD FEB PY 2012 VL 7 IS 2 BP 408 EP 419 DI 10.1038/nprot.2011.451 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 894BP UT WOS:000300402300016 PM 22301778 ER PT J AU Skinner, M AF Skinner, Mhairi TI CANCER STEM CELLS TAZ takes centre stage SO NATURE REVIEWS CANCER LA English DT News Item C1 NCI Nat Pathway Interact Database, Rockville, MD 20852 USA. RP Skinner, M (reprint author), NCI Nat Pathway Interact Database, Rockville, MD 20852 USA. NR 0 TC 2 Z9 3 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD FEB PY 2012 VL 12 IS 2 BP 82 EP 82 DI 10.1038/nrc3210 PG 1 WC Oncology SC Oncology GA 892BN UT WOS:000300261700005 PM 22257952 ER PT J AU Hunter, KW AF Hunter, Kent W. TI Mouse models of cancer: does the strain matter? SO NATURE REVIEWS CANCER LA English DT Review ID BREAST-CANCER; INTESTINAL NEOPLASIA; TUMOR-SUSCEPTIBILITY; GENETIC-ANALYSIS; COMPLEX TRAITS; MICE; POLYMORPHISMS; METASTASIS; CANDIDATE; MODIFIER AB Mouse models are indispensible tools for understanding the molecular basis of cancer. However, despite the invaluable data provided regarding tumour biology, owing to inbreeding, current mouse models fail to accurately model human populations. Polymorphism is the essential characteristic that makes each of us unique humans, with different disease susceptibility, presentation and progression. Therefore, as we move closer towards designing clinical treatment that is based on an individual's unique biological makeup, it is imperative that we understand how inherited variability influences cancer phenotypes, how it can confound experiments and how it can be exploited to reveal new truths about cancer biology. C1 NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Hunter, KW (reprint author), NCI, Lab Canc Biol & Genet, NIH, 37-5046,37 Convent Dr, Bethesda, MD 20892 USA. EM hunterk@mail.nih.gov FU US National Institutes of Health, National Cancer Institute, Center for Cancer Research FX I would like to thank J. Alsarraj and D. Threadgill for their insightful comments on this article. I would also like to apologize to the many investigators whose work was not discussed in this article owing to space constraints. This work was supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 31 TC 21 Z9 21 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD FEB PY 2012 VL 12 IS 2 BP 144 EP U1 DI 10.1038/nrc3206 PG 6 WC Oncology SC Oncology GA 892BN UT WOS:000300261700013 PM 22257951 ER PT J AU Sfanos, KS Aloia, AL De Marzo, AM Rein, A AF Sfanos, Karen S. Aloia, Amanda L. De Marzo, Angelo M. Rein, Alan TI XMRV and prostate cancer-a 'final' perspective SO NATURE REVIEWS UROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; CHRONIC-FATIGUE-SYNDROME; NO EVIDENCE; RETROVIRUS XMRV; INFECTIOUS RETROVIRUS; SEQUENCE VARIATION; INTEGRATION SITES; UNITED-STATES; BLOOD-DONORS; MOUSE DNA AB XMRV was first described in 2006, when it was identified in samples isolated from prostate cancer tissues. However, studies have since shown that XMRV arose in the laboratory and was formed by genetic recombination between two viral genomes carried in the germline DNA of mice used during serial transplantation of the CWR22 prostate cancer xenograft. These new findings strongly imply that XMRV does not circulate in humans, but is only present in the laboratory. Thus, there is no reason to believe that it has any role in the etiology of prostate cancer or other diseases. C1 [Sfanos, Karen S.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA. [Aloia, Amanda L.; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [De Marzo, Angelo M.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. [De Marzo, Angelo M.] Johns Hopkins Univ, Sch Med, Brady Urol Res Inst, Baltimore, MD 21231 USA. RP Sfanos, KS (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA. EM ksfanos@jhmi.edu OI De Marzo, Angelo/0000-0003-4847-5307 FU NIH, National Cancer Institute, Center for Cancer Research FX The authors would like to acknowledge Dr Saraswati Sukumar for helpful discussions. Research by A. Aloia and A. Rein is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 67 TC 13 Z9 13 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4812 J9 NAT REV UROL JI Nat. Rev. Urol. PD FEB PY 2012 VL 9 IS 2 BP 111 EP 118 DI 10.1038/nrurol.2011.225 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 894HA UT WOS:000300416500010 PM 22231291 ER PT J AU Rao, M Mottl, AK Cole, SA Umans, JG Freedman, BI Bowden, DW Langefeld, CD Fox, CS Yang, Q Cupples, A Iyengar, SK Hunt, SC Trikalinos, TA AF Rao, Madhumathi Mottl, Amy K. Cole, Shelley A. Umans, Jason G. Freedman, Barry I. Bowden, Donald W. Langefeld, Carl D. Fox, Caroline S. Yang, Qiong Cupples, Adrienne Iyengar, Sudha K. Hunt, Steven C. Trikalinos, Thomas A. TI Meta-analysis of genome-wide linkage scans for renal function traits SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE albuminuria; chronic kidney disease; glomerular filtration rate; linkage scans; meta-analysis ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; GENES-CONTROLLING VARIATION; URINARY ALBUMIN EXCRETION; TYPE-2 DIABETES-MELLITUS; COMMUNITY-BASED SAMPLE; SEARCH METAANALYSIS; AFRICAN-AMERICANS; SERUM CREATININE; MEXICAN-AMERICANS AB Several genome scans have explored the linkage of chronic kidney disease phenotypes to chromosomic regions with disparate results. Genome scan meta-analysis (GSMA) is a quantitative method to synthesize linkage results from independent studies and assess their concordance. We searched PubMed to identify genome linkage analyses of renal function traits in humans, such as estimated glomerular filtration rate (GFR), albuminuria, serum creatinine concentration and creatinine clearance. We contacted authors for numerical data and extracted information from individual studies. We applied the GSMA nonparametric approach to combine results across 14 linkage studies for GFR, 11 linkage studies for albumin creatinine ratio, 11 linkage studies for serum creatinine and 4 linkage studies for creatinine clearance. No chromosomal region reached genome-wide statistical significance in the main analysis which included all scans under each phenotype; however, regions on Chromosomes 7, 10 and 16 reached suggestive significance for linkage to two or more phenotypes. Subgroup analyses by disease status or ethnicity did not yield additional information. While heterogeneity across populations, methodologies and study designs likely explain this lack of agreement, it is possible that linkage scan methodologies lack the resolution for investigating complex traits. Combining family-based linkage studies with genome-wide association studies may be a powerful approach to detect private mutations contributing to complex renal phenotypes. C1 [Trikalinos, Thomas A.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Ctr Clin Evidence Synth, Boston, MA 02111 USA. [Rao, Madhumathi] Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA. [Mottl, Amy K.] Univ N Carolina, Sch Med, UNC Kidney Ctr, Chapel Hill, NC USA. [Cole, Shelley A.] SW Fdn Biomed Res, San Antonio, TX 78284 USA. [Umans, Jason G.] Georgetown Univ, Med Ctr, Dept Med Obstet & Gynecol, Gen Clin Res Ctr, Washington, DC 20007 USA. [Freedman, Barry I.; Bowden, Donald W.; Langefeld, Carl D.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom & Publ Hlth Sci, Winston Salem, NC USA. [Fox, Caroline S.] NHLBI, NHLBIs Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] NHLBI, Ctr Populat Sci, Framingham, MA USA. [Yang, Qiong; Cupples, Adrienne] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Iyengar, Sudha K.] Case Western Reserve Univ, Div Genet & Mol Epidemiol, Cleveland, OH 44106 USA. [Hunt, Steven C.] Univ Utah, Dept Internal Med, Cardiovasc Genet Div, Salt Lake City, UT 84112 USA. RP Trikalinos, TA (reprint author), Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Ctr Clin Evidence Synth, Boston, MA 02111 USA. EM ttrikalinos@tuftsmedicalcenter.org RI Yang, Qiong/G-5438-2014; OI Mottl, Amy/0000-0002-4258-1726 FU National Institutes of Health [DK066992, R01 DK053591, R01 HL56266, R01 DK070941, DK084149, N01-HG-65403]; Tufts Clinical and Translational Science Institute [1 UL1 RR025752-02]; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; General Clinical Research Center of the Wake Forest University School of Medicine [M01 RR07122]; HyperGEN study [HL54471, HL54472, HL54473, HL54495, HL54496, HL54497, HL54509, HL54515, HL55673]; NIDDK [U01DK57292, U01DK57249, U01DK57295, U01DK57298, U01DK57300, U01DK57303, U01DK57304, U01DK57329]; National Center for Research Resources for the General Clinical Research Center: Case Western Reserve University [M01-RR-000080]; National Center for Research Resources for the General Clinical Research Center: Wake Forest University [M01-RR-07122]; National Center for Research Resources for the General Clinical Research Center: Harbor-UCLA Medical Center [M01-RR-00425]; National Center for Research Resources for the General Clinical Research Center: College of Medicine-University of California Irvine [M01-RR-00827-29]; National Center for Research Resources for the General Clinical Research Center: University of New Mexico HSC [M01-RR-00997]; National Center for Research Resources for the General Clinical Research Center: [M01-RR-01346]; [R01-AG18734] FX This work was supported by (i) National Institutes of Health (DK066992) to Dr Rao; (ii) Grant 1 UL1 RR025752-02, Tufts Clinical and Translational Science Institute; (iii) the National Heart, Lung and Blood Institute's Framingham Heart Study (N01-HC-25195); (iv) Wake Forest analyses were supported by National Institutes of Health grants (R01 DK053591 to D. W. B.), (R01 HL56266 to B. I. F.), (R01 DK070941 to B. I. F.), (DK084149 to B. I. F.) and, in part, by the General Clinical Research Center of the Wake Forest University School of Medicine grant M01 RR07122; (v) HyperGEN study (HL54471, HL54472, HL54473, HL54495, HL54496, HL54497, HL54509, HL54515 and HL55673); (vi) (R01-AG18734); (vii) The FIND study was supported by Research Grants (U01DK57292, U01DK57249, U01DK57295, U01DK57298, U01DK57300, U01DK57303, U01DK57304 and U01DK57329) from the NIDDK and, in part, by the Intramural Research Program of the NIDDK. This work was also supported by the National Center for Research Resources for the General Clinical Research Center grants: Case Western Reserve University (M01-RR-000080), Wake Forest University (M01-RR-07122), Harbor-UCLA Medical Center (M01-RR-00425), College of Medicine-University of California Irvine (M01-RR-00827-29), University of New Mexico HSC (M01-RR-00997) and Frederic C. Bartter (M01-RR-01346).; Genotyping for the original studies was performed by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University, contract no. N01-HG-65403. NR 57 TC 7 Z9 7 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD FEB PY 2012 VL 27 IS 2 BP 647 EP 656 DI 10.1093/ndt/gfr255 PG 10 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 894IV UT WOS:000300421300029 PM 21622988 ER PT J AU Amlin-Van Schaick, JC Kim, S DiFabio, C Lee, MH Broman, KW Reilly, KM AF Amlin-Van Schaick, Jessica C. Kim, Sungjin DiFabio, Christina Lee, Min-Hyung Broman, Karl W. Reilly, Karlyne M. TI Arlm1 is a male-specific modifier of astrocytoma resistance on mouse Chr 12 SO NEURO-ONCOLOGY LA English DT Article DE astrocytoma; glioblastoma; modifier; sex differences ID INTEGRATED GENOMIC ANALYSIS; GLIOBLASTOMA-MULTIFORME; INCREASED EXPRESSION; MONOAMINE-OXIDASE; WIDE ASSOCIATION; IMMUNE-RESPONSE; BREAST-CANCER; CONDENSIN-II; ADULT GLIOMA; GENES AB While many cancers show a sex bias, the genetic basis and molecular mechanisms underlying sex bias are not always clear. Astrocytoma and glioblastoma show male predominance in humans. We have shown previously that glial tumors forming in the Nf1-/+; Trp53-/+cis (NPcis) mouse model also show a sex bias in some genetic contexts. Using cross-species comparisons we have identified candidate male-specific modifiers of astrocytoma/glioblastoma. Linkage analysis of B6X(B6X129)-NPcis mice identifies a modifier of astrocytoma resistance specific to males, named Arlm1, on distal mouse Chr 12. Arlm1 is syntenic to human Chr 7p15, 7p21, 7q36, and 14q32 regions that are altered in human glioblastoma. A subset of these genes shows male-specific correlations to glioblastoma patient survival time and represents strong candidates for the Arlm1 modifier gene. Identification of male-specific modifier genes will lead to a better understanding of the molecular basis of male predominance in astrocytoma and glioblastoma. C1 [Amlin-Van Schaick, Jessica C.; DiFabio, Christina; Lee, Min-Hyung; Reilly, Karlyne M.] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. [Amlin-Van Schaick, Jessica C.] George Washington Univ, Inst Biomed Sci, Washington, DC USA. [Kim, Sungjin; Broman, Karl W.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI USA. RP Reilly, KM (reprint author), NCI, Mouse Canc Genet Program, W 7th St,POB B, Frederick, MD 21702 USA. EM reillyk@mail.nih.gov OI Broman, Karl/0000-0002-4914-6671 FU National Institutes of Health, National Cancer Institute [ZIA BC 010539]; National Cancer Institute [N01-CO-12400]; National Institutes of Health [HHSN268200782096C, R01 GM074244] FX Intramural Research Program of the National Institutes of Health, National Cancer Institute [ZIA BC 010539 to K. M. R.]; federal funds from the National Cancer Institute to SAIC Frederick [contract N01-CO-12400]; federal contract from the National Institutes of Health to The Johns Hopkins University [contract HHSN268200782096C]; extramural funding from the National Institutes of Health [R01 GM074244 to K.W.B.]. NR 68 TC 12 Z9 12 U1 0 U2 1 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 160 EP 174 DI 10.1093/neuonc/nor206 PG 15 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 892QO UT WOS:000300300900004 PM 22234937 ER PT J AU Tuo, JS Grob, S Zhang, K Chan, CC AF Tuo, Jingsheng Grob, Seanna Zhang, Kang Chan, Chi-Chao TI Genetics of Immunological and Inflammatory Components in Age-related Macular Degeneration SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE age-related macular degeneration (AMD); complement factor; cytokine/chemokine; gene; innate immunity ID COMPLEMENT-FACTOR-H; POLYPOIDAL CHOROIDAL VASCULOPATHY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; COPY-NUMBER VARIATION; HTRA1 PROMOTER POLYMORPHISM; TOLL-LIKE RECEPTOR-3; PHOTODYNAMIC THERAPY; SUSCEPTIBILITY LOCI; LOC387715 GENOTYPES AB Age-related macular degeneration (AMD), affecting 30 to 50 million elder individuals worldwide, is a disease affecting the macular retina and choroid that can lead to irreversible central vision loss and blindness. Recent findings support a role for immunologic processes in AMD pathogenesis, including generation of inflammatory related molecules in the Bruch's membrane, recruitment of macrophages, complement activation, microglial activation and accumulation in the macular lesions. Pro-inflammatory effects of chronic inflammation and oxidative stress can result in abnormal retinal pigment epithelium, photoreceptor atrophy and choroidal neovascularization. The associations of immunological and inflammatory genes, in particular the genes related to innate immunity with AMD support the involvement of various immunological pathways in the AMD pathogenesis. We review the literature on the involvements of inflammatory genes in AMD, highlight recent genetic discoveries, and discuss the potential application of such knowledge in the management of patients with AMD. C1 [Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Grob, Seanna; Zhang, Kang] Univ Calif San Diego, Dept Ophthalmol, La Jolla, CA 92093 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810 FU NEI FX The NEI Intramural Research program provided funding. NR 119 TC 40 Z9 42 U1 1 U2 11 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 27 EP 36 DI 10.3109/09273948.2011.628432 PG 10 WC Ophthalmology SC Ophthalmology GA 892AO UT WOS:000300259000006 PM 22324898 ER PT J AU Bellizzi, K Smith, A Schmidt, S Keegan, T Zebrack, B Lynch, C Deapen, D Shnorhavorian, M AF Bellizzi, K. Smith, A. Schmidt, S. Keegan, T. Zebrack, B. Lynch, C. Deapen, D. Shnorhavorian, M. TI Positive and Negative Life Impact of Being Diagnosed With Cancer as an Adolescent or Young Adult SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Bellizzi, K.; Schmidt, S.] Univ Connecticut, Storrs, CT USA. [Smith, A.] NCI, Bethesda, MD 20892 USA. [Keegan, T.] Canc Prevent Inst Calif, Fremont, CA USA. [Keegan, T.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Zebrack, B.] Univ Michigan, Ann Arbor, MI 48109 USA. [Lynch, C.] Univ Iowa, Iowa City, IA USA. [Deapen, D.] Univ So Calif, Los Angeles, CA USA. [Shnorhavorian, M.] Seattle Childrens Hosp, Seattle, WA 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 5 EP 6 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800010 ER PT J AU Kent, EE Smith, AW Keegan, THM Lynch, C Wu, XC Hamilton, AS Kato, I Schwartz, S Harlan, LC AF Kent, E. E. Smith, A. W. Keegan, T. H. M. Lynch, C. Wu, X.-C. Hamilton, A. S. Kato, I. Schwartz, S. Harlan, L. C. TI Social Support Needs in Adolescents and Young Adults Diagnosed With Cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Kent, E. E.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Smith, A. W.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. [Keegan, T. H. M.] Canc Prevent Inst Calif, Fremont, CA USA. [Keegan, T. H. M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Lynch, C.] Univ Iowa, Iowa City, IA USA. [Wu, X.-C.] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, Epidemiol Program,Louisiana Tumor Registry, New Orleans, LA USA. [Hamilton, A. S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Kato, I.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Kato, I.] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI USA. [Schwartz, S.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Harlan, L. C.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 SU 1 SI SI BP 5 EP 5 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800009 ER PT J AU Ludi, E Margolis, R Wiener, L Pao, M AF Ludi, E. Margolis, R. Wiener, L. Pao, M. TI Understanding the Biopsychosocial Experience of International Families: Adaptation and Challenges SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Ludi, E.; Pao, M.] NIMH, NIH, Bethesda, MD 20892 USA. [Margolis, R.] NIH, Ctr Clin, Dept Social Work, Bethesda, MD 20892 USA. [Wiener, L.] NCI, NIH, Bethesda, MD 20892 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 8 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800013 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 Horowitz, L AF Horowitz, L. TI When Race Really Does Matter: Racial and Ethnic Disparities in the Bone Marrow Registry SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Horowitz, L.] NIMH, Bethesda, MD 20892 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 9 EP 10 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800016 ER PT J AU Wiener, L Zadeh, S Battles, H Pao, M AF Wiener, L. Zadeh, S. Battles, H. Pao, M. TI Can an Adapted Distress Thermometer in the Pediatric Population Be Valid and Clinically Meaningful? SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Wiener, L.; Zadeh, S.; Battles, H.] NCI, NIH, Bethesda, MD 20892 USA. [Pao, M.] NIMH, NIH, Bethesda, MD 20892 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 27 EP 27 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800047 ER PT J AU Zadeh, S Wiener, L Battles, H Pao, M AF Zadeh, S. Wiener, L. Battles, H. Pao, M. TI Parent and Provider Ratings of Patient Distress: Are They Valid and/or Meaningful? SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Zadeh, S.; Wiener, L.; Battles, H.] NCI, NIH, Bethesda, MD 20892 USA. [Pao, M.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 27 EP 28 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800048 ER PT J AU Bevans, M AF Bevans, M. TI Distress Screening in Transplant Family Caregivers: What Have We Learned? SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Bevans, M.] NIH, Ctr Clin, Bethesda, MD 20892 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 28 EP 28 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800049 ER PT J AU Lichtenthal, W Wiener, L Sweeney, C Roberts, K Farberov, M AF Lichtenthal, W. Wiener, L. Sweeney, C. Roberts, K. Farberov, M. TI Disparities in Prolonged Grief, Mental Health Service Use, and Barriers to Use in Racial/Ethnic Minority Parents Bereaved by Cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Lichtenthal, W.; Sweeney, C.; Roberts, K.; Farberov, M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wiener, L.] NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 40 EP 40 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800070 ER PT J AU Snyder, D Horowitz, L Ludi, E Kohn, J Rosenstein, D Pao, M AF Snyder, D. Horowitz, L. Ludi, E. Kohn, J. Rosenstein, D. Pao, M. TI Just ASQ'em: Screening for Suicide in Hospitalized Cancer Patients SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Snyder, D.; Horowitz, L.; Ludi, E.; Pao, M.] NIMH, Bethesda, MD 20892 USA. [Kohn, J.] NIH, Clin Res Ctr, Bethesda, MD 20892 USA. [Rosenstein, D.] Univ N Carolina, Chapel Hill, NC 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 47 EP 48 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800082 ER PT J AU Chuang, PY Conley, Y Kuo, CWJ Sherwood, P AF Chuang, P-Y Conley, Y. Kuo, C. W-J Sherwood, P. TI Functional Interleukin 1 beta and 6 Proteins and Their Genetic Variations Associated With Psycho-behavioral Responses in the Caregivers of Patients With Malignant Brain Tumors SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Chuang, P-Y] NINR, NIH, Bethesda, MD 20892 USA. [Conley, Y.; Kuo, C. W-J; Sherwood, P.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 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 66 EP 67 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800117 ER PT J AU Wiener, L McConnell, D Latella, L Ludi, E AF Wiener, L. McConnell, D. Latella, L. Ludi, E. TI Cultural and Religious Considerations in Pediatric Palliative Care SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Wiener, L.] NCI, NIH, Bethesda, MD 20892 USA. [Latella, L.] Cornell Univ, Ithaca, NY USA. [Ludi, E.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 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 90 EP 90 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800159 ER PT J AU Zadeh, S Wiener, L AF Zadeh, S. Wiener, L. TI When Cure No Longer Seems Possible: Support for Patients, Families and Health Care Staff SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Zadeh, S.; Wiener, L.] NCI, NIH, Bethesda, MD 20892 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 90 EP 91 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800160 ER PT J AU Forsythe, LP Alfano, CM Kent, EE Weaver, KE Rowland, JH AF Forsythe, L. P. Alfano, C. M. Kent, E. E. Weaver, K. E. Rowland, J. H. TI Social Support in Cancer Survivors: Individual Differences and Associations With Follow-up Care SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Forsythe, L. P.; Alfano, C. M.; Kent, E. E.; Rowland, J. H.] NCI, Off Canc Survivorship, NIH, DHHS, Bethesda, MD 20892 USA. [Weaver, K. E.] Wake Forest Univ Hlth Sci, Winston Salem, NC 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 124 EP 125 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 885LP UT WOS:000299780800223 ER PT J AU Tai, B Boyle, M Ghitza, U Kaplan, RM Clark, HW Gersing, K AF Tai, Betty Boyle, Maureen Ghitza, Udi Kaplan, Robert M. Clark, H. Westley Gersing, Kenneth TI Meaningful Use of Electronic Behavioral Health Data in Primary Health Care SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material AB In August 2011, scientists and policy-makers held a conference entitled "Using IT to Improve Community Health: How Health Care Reform Supports Innovation." One of the conference sessions was entitled "Electronic health records: Meaningful use implementation challenges, innovation, and regulations." This meeting report discusses the meaningful use of behavioral health data for the treatment of mental health and substance abuse conditions and optimization of behavioral wellness by primary care physicians. C1 [Tai, Betty; Ghitza, Udi] Natl Inst Drug Abuse, Ctr Clin Trials Network, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Boyle, Maureen; Kaplan, Robert M.] NIH, Off Behav & Social Sci Res, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Clark, H. Westley] Subst Abuse & Mental Hlth Serv Adm, US Dept Hlth & Human Serv, Rockville, MD 20857 USA. [Gersing, Kenneth] Duke Univ, Dept Psychiat & Behav Sci, Sch Med, Med Ctr, Durham, NC 27710 USA. RP Tai, B (reprint author), Natl Inst Drug Abuse, Ctr Clin Trials Network, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM btai@nih.gov NR 6 TC 3 Z9 3 U1 0 U2 5 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 FEB 1 PY 2012 VL 4 IS 119 AR 119mr3 DI 10.1126/scitranslmed.3003324 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 891NG UT WOS:000300223300004 PM 22301552 ER PT J AU Gershengorn, MC AF Gershengorn, Marvin C. TI History of the Clinical Endocrinology Branch of the National Institute of Diabetes and Digestive and Kidney Diseases: Impact on Understanding and Treatment of Diseases of the Thyroid Gland SO THYROID LA English DT Editorial Material ID RADIOACTIVE IODINE; HORMONE; RECEPTOR; SECRETION; MECHANISM; MICE C1 NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA. RP Gershengorn, MC (reprint author), NIDDK, Lab Endocrinol & Receptor Biol, NIH, 50 South Dr,Room 4134, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov FU Intramural NIH HHS NR 18 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 1050-7256 J9 THYROID JI Thyroid PD FEB PY 2012 VL 22 IS 2 BP 109 EP 111 DI 10.1089/thy.2012.2202.com PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 891TY UT WOS:000300240700001 PM 22257372 ER PT J AU Schonfeld, SJ Neta, G Sturgis, EM Pfeiffer, RM Hutchinson, AA Xu, L Wheeler, W Guenel, P Rajaraman, P de Vathaire, F Ron, E Tucker, MA Chanock, SJ Sigurdson, AJ Brenner, AV AF Schonfeld, Sara J. Neta, Gila Sturgis, Erich M. Pfeiffer, Ruth M. Hutchinson, Amy A. Xu, Li Wheeler, William Guenel, Pascal Rajaraman, Preetha de Vathaire, Florent Ron, Elaine Tucker, Margaret A. Chanock, Stephen J. Sigurdson, Alice J. Brenner, Alina V. TI Common Genetic Variants in Sex Hormone Pathway Genes and Papillary Thyroid Cancer Risk SO THYROID LA English DT Article ID US RADIOLOGIC TECHNOLOGISTS; POLYMORPHISMS; ASSOCIATION; CARCINOMA; ESTROGEN; GENDER; AGE AB Background: Hormonal differences are hypothesized to contribute to the approximately >= 2-fold higher thyroid cancer incidence rates among women compared with men worldwide. Although thyroid cancer cells express estrogen receptors and estrogen has a proliferative effect on papillary thyroid cancer (PTC) cells in vitro, epidemiologic studies have not found clear associations between thyroid cancer and female hormonal factors. We hypothesized that polymorphic variation in hormone pathway genes is associated with the risk of developing papillary thyroid cancer. Methods: We evaluated the association between PTC and 1151 tag single nucleotide polymorphisms (SNPs) in 58 candidate gene regions involved in sex hormone synthesis and metabolism, gonadotropins, and prolactin in a case-control study of 344 PTC cases and 452 controls, frequency matched on age and sex. Odds ratios and p-values for the linear trend for the association between each SNP genotype and PTC risk were estimated using unconditional logistic regression. SNPs in the same gene region or pathway were aggregated using adaptive rank-truncated product methods to obtain gene region-specific or pathway-specific p-values. To account for multiple comparisons, we applied the false discovery rate method. Results: Seven SNPs had p-values for linear trend <0.01, including four in the CYP19A1 gene, but none of the SNPs remained significant after correction for multiple comparisons. Results were similar when restricting the dataset to women. p-values for examined gene regions and for all genes combined were >= 0.09. Conclusions: Based on these results, SNPs in selected hormone pathway genes do not appear to be strongly related to PTC risk. This observation is in accord with the lack of consistent associations between hormonal factors and PTC risk in epidemiologic studies. C1 [Schonfeld, Sara J.; Neta, Gila; Pfeiffer, Ruth M.; Rajaraman, Preetha; Ron, Elaine; Tucker, Margaret A.; Sigurdson, Alice J.; Brenner, Alina V.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Sturgis, Erich M.; Xu, Li] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. [Sturgis, Erich M.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Hutchinson, Amy A.] SAIC Frederick Inc, Core Genotyping Facil, Gaithersburg, MD USA. [Hutchinson, Amy A.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Adv Technol Ctr, Gaithersburg, MD USA. [Wheeler, William] Informat Management Syst, Rockville, MD USA. [Guenel, Pascal] Natl Inst Hlth & Med Res, INSERM, CESP, Ctr Res Epidemiol & Populat Hlth, Villejuif, France. [Guenel, Pascal; de Vathaire, Florent] Univ Paris 11, Villejuif, France. [de Vathaire, Florent] INSERM, Radiat Epidemiol Grp, Villejuif, France. [de Vathaire, Florent] Inst Gustave Roussy, Villejuif, France. RP Schonfeld, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, Executive Plaza S,MSC 7238,6120 Execut Blvd, Bethesda, MD 20892 USA. EM schonfes@mail.nih.gov RI Xu, Li/B-9535-2012; Tucker, Margaret/B-4297-2015; de Vathaire, Florent/L-2983-2016 FU American Registry of Radiologic Technologists; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health; American Thyroid Association; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX The authors are indebted to Elaine Ron's long-term commitment to understanding causes and prevention of thyroid cancer. Her inspiration, vision, and leadership were integral to this project. They are grateful to the radiologic technologists who participated in the USRT Study; Jerry Reid of the American Registry of Radiologic Technologists for continued support of this study; Diane Kampa and Allison Iwan of the University of Minnesota for data collection and study coordination; Liliana Mugartegui for patient recruitment, data collection, and study coordination at the University of Texas M. D. Anderson Cancer Center; and Laura Bowen of Information Management Systems for biomedical computing statistical support. This research was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, and by a grant from the American Thyroid Association (PI: E.M.S.). This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does it mention trade names, commercial products, or organizations implying endorsement by the U.S. Government. NR 19 TC 9 Z9 10 U1 0 U2 3 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 151 EP 156 DI 10.1089/thy.2011.0309 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 891TY UT WOS:000300240700009 PM 22224819 ER PT J AU Heidebrecht, RW Mulrooney, C Austin, CP Barker, RH Beaudoin, JA Cheng, KCC Comer, E Dandapani, S Dick, J Duvall, JR Ekland, EH Fidock, DA Fitzgerald, ME Foley, M Guha, R Hinkson, P Kramer, M Lukens, AK Masi, D Marcaurelle, LA Su, XZ Thomas, CJ Weiwer, M Wiegand, RC Wirth, D Xia, MH Yuan, J Zhao, JH Palmer, M Munoz, B Schreiber, S AF Heidebrecht, Richard W., Jr. Mulrooney, Carol Austin, Christopher P. Barker, Robert H., Jr. Beaudoin, Jennifer A. Cheng, Ken Chih-Chien Comer, Eamon Dandapani, Sivaraman Dick, Justin Duvall, Jeremy R. Ekland, Eric H. Fidock, David A. Fitzgerald, Mark E. Foley, Michael Guha, Rajarshi Hinkson, Paul Kramer, Martin Lukens, Amanda K. Masi, Daniela Marcaurelle, Lisa A. Su, Xin-Zhuan Thomas, Craig J. Weiwer, Michel Wiegand, Roger C. Wirth, Dyann Xia, Menghang Yuan, Jing Zhao, Jinghua Palmer, Michelle Munoz, Benito Schreiber, Stuart TI Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE diversity-oriented synthesis; malaria; macrocycle; high-throughput screening phenotypic screen; infectious disease; molecular libraries probe production centers; stereochemical structure-activity relationships ID FALCIPARUM DIHYDROOROTATE DEHYDROGENASE; PLASMODIUM-FALCIPARUM; NATURAL-PRODUCT; DRUG DISCOVERY; INHIBITORS; STRATEGY; IDENTIFICATION; ANTIMALARIALS; ERADICATION; MOLECULES AB Here, we describe the discovery of a novel antimalarial agent using phenotypic screening of Plasmodium falciparum asexual blood-stage parasites. Screening a novel compound collection created using diversity-oriented synthesis (DOS) led to the initial hit. Structure activity relationships guided the synthesis of compounds having improved potency and water solubility, yielding a subnanomolar inhibitor of parasite asexual blood-stage growth. Optimized compound 27 has an excellent off-target activity profile in erythrocyte lysis and HepG2 assays and is stable in human plasma. This compound is available via the molecular libraries probe production centers network (MLPCN) and is designated ML238. C1 [Heidebrecht, Richard W., Jr.; Mulrooney, Carol; Beaudoin, Jennifer A.; Comer, Eamon; Dandapani, Sivaraman; Duvall, Jeremy R.; Fitzgerald, Mark E.; Foley, Michael; Lukens, Amanda K.; Masi, Daniela; Marcaurelle, Lisa A.; Weiwer, Michel; Wiegand, Roger C.; Wirth, Dyann; Palmer, Michelle; Munoz, Benito; Schreiber, Stuart] Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Austin, Christopher P.; Cheng, Ken Chih-Chien; Guha, Rajarshi; Thomas, Craig J.; Xia, Menghang; Zhao, Jinghua] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Heidebrecht, Richard W., Jr.; Dick, Justin; Lukens, Amanda K.; Wiegand, Roger C.; Wirth, Dyann] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ekland, Eric H.; Fidock, David A.] Colombia Univ, Dept Microbiol & Immunol, New York, NY 10032 USA. [Fidock, David A.] Colombia Univ, Dept Med, Div Infect Dis, New York, NY 10032 USA. [Su, Xin-Zhuan; Yuan, Jing] NIAID, Bethesda, MD 20892 USA. [Schreiber, Stuart] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Barker, Robert H., Jr.; Hinkson, Paul; Kramer, Martin] Genzyme Corp, Waltham, MA 02451 USA. RP Heidebrecht, RW (reprint author), Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. EM richardh@broadinstitute.org OI Fidock, David/0000-0001-6753-8938; Su, Xinzhuan/0000-0003-3246-3248 FU NIH-MLPCN [1 U54 HG005032-1, 5 U54MH08468-1]; NIGMS (Broad Institute CMLD) [50 GM069721]; NIH [R01 AI079709]; Genzyme FX This work was funded by the NIH-MLPCN program (1 U54 HG005032-1 awarded to S.L.S. and 5 U54MH08468-1 awarded to C.P.A.) and the NIGMS-sponsored Center of Excellence in Chemical Methodology and Library Development (Broad Institute CMLD; P50 GM069721). Funding for EHE and DAF was provided in part by the NIH (R01 AI079709). Funding for specificity testing was provided by Genzyme. NR 28 TC 28 Z9 28 U1 5 U2 41 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD FEB PY 2012 VL 3 IS 2 BP 112 EP 117 DI 10.1021/ml200244k PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 890EA UT WOS:000300126700007 ER PT J AU Kramer, MS Papageorghiou, A Culhane, J Bhutta, Z Goldenberg, RL Gravett, M Iams, JD Conde-Agudelo, A Waller, S Barros, F Knight, H Villar, J AF Kramer, Michael S. Papageorghiou, Aris Culhane, Jennifer Bhutta, Zulfiqar Goldenberg, Robert L. Gravett, Michael Iams, Jay D. Conde-Agudelo, Agustin Waller, Sarah Barros, Fernando Knight, Hannah Villar, Jose TI Challenges in defining and classifying the preterm birth syndrome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material DE classification; phenotype; preterm birth ID GESTATIONAL-AGE ESTIMATION; UNITED-STATES; BACTERIAL-VAGINOSIS; PERINATAL-MORTALITY; RISK-FACTORS; DELIVERY; WEIGHT; PREGNANCY; GROWTH; TERM AB In 2009, the Global Alliance to Prevent Prematurity and Stillbirth Conference charged the authors to propose a new comprehensive, consistent, and uniform classification system for preterm birth. This first article reviews issues related to measurement of gestational age, clinical vs etiologic phenotypes, inclusion vs exclusion of multifetal and stillborn infants, and separation vs combination of pathways to preterm birth. The second article proposes answers to the questions raised here, and the third demonstrates how the proposed system might work in practice. C1 [Iams, Jay D.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Kramer, Michael S.] McGill Univ, Dept Pediat, Fac Med, Montreal, PQ H3A 2T5, Canada. [Kramer, Michael S.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Fac Med, Montreal, PQ H3A 2T5, Canada. [Papageorghiou, Aris; Knight, Hannah; Villar, Jose] Univ Oxford, Nuffield Dept Obstet & Gynecol, Oxford, England. [Papageorghiou, Aris; Knight, Hannah; Villar, Jose] Univ Oxford, Oxford Maternal & Perinatal Hlth Inst, Green Templeton Coll, Oxford, England. [Culhane, Jennifer] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Bhutta, Zulfiqar] Aga Khan Univ, Div Women & Child Hlth, Karachi, Pakistan. [Goldenberg, Robert L.] Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Gravett, Michael; Waller, Sarah] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Gravett, Michael] Seattle Childrens Hosp, Seattle, WA USA. [Conde-Agudelo, Agustin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Conde-Agudelo, Agustin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Barros, Fernando] Univ Catolica Pelotas, Postgrad Course Hlth & Behav, Pelotas, RS, Brazil. RP Iams, JD (reprint author), Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. EM Jay.Iams@osumc.edu RI Epidemiologicas, Centro de pesquisas /D-4561-2013; Barros, Fernando/D-4857-2013 NR 61 TC 57 Z9 58 U1 0 U2 14 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2012 VL 206 IS 2 BP 108 EP 112 DI 10.1016/j.ajog.2011.10.864 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 886FA UT WOS:000299836800011 PM 22118964 ER PT J AU Goldenberg, RL Gravett, MG Iams, J Papageorghiou, AT Waller, SA Kramer, M Culhane, J Barros, F Conde-Agudelo, A Bhutta, ZA Knight, HE Villar, J AF Goldenberg, Robert L. Gravett, Michael G. Iams, Jay Papageorghiou, Aris T. Waller, Sarah A. Kramer, Michael Culhane, Jennifer Barros, Fernando Conde-Agudelo, Augustin Bhutta, Zulfiqar A. Knight, Hannah E. Villar, Jose TI The preterm birth syndrome: issues to consider in creating a classification system SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material DE classification; phenotype; preterm birth ID 2ND-TRIMESTER PREGNANCY LOSS; PERINATAL-MORTALITY; BACTERIAL VAGINOSIS; NEONATAL OUTCOMES; RISK-FACTORS; DELIVERY; TERM; HETEROGENEITY; STILLBIRTH; SUBTYPES AB A comprehensive classification system for preterm birth requires expanded gestational boundaries that recognize the early origins of preterm parturition and emphasize fetal maturity over fetal age. Exclusion of stillbirths, pregnancy terminations, and multifetal gestations prevents comprehensive consideration of the potential causes and presentations of preterm birth. Any step in parturition (cervical softening and ripening, decidual-membrane activation, and/or myometrial contractions) may initiate preterm parturition, and should be recorded for every preterm birth, as should the condition of the mother, fetus, newborn, and placenta, before a phenotype is assigned. C1 [Goldenberg, Robert L.] Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Gravett, Michael G.; Waller, Sarah A.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Seattle Childrens, Global Alliance Prevent Prematur & Stillbirth, Seattle, WA USA. [Iams, Jay] Ohio State Univ, Dept Obstet & Gynecol, Med Ctr, Div Maternal Fetal Med, Columbus, OH 43210 USA. [Papageorghiou, Aris T.; Knight, Hannah E.; Villar, Jose] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England. Univ Oxford, Oxford Maternal & Perinatal Hlth Inst, Green Templeton Coll, Oxford, England. [Kramer, Michael] McGill Univ, Dept Pediat, Fac Med, Montreal, PQ H3A 2T5, Canada. [Kramer, Michael] McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 2T5, Canada. [Culhane, Jennifer] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. [Barros, Fernando] Univ Catolica Pelotas, Postgrad Course Hlth & Behav, Pelotas, RS, Brazil. [Conde-Agudelo, Augustin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Conde-Agudelo, Augustin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Bhutta, Zulfiqar A.] Aga Khan Univ, Div Women & Child Hlth, Karachi, Pakistan. RP Goldenberg, RL (reprint author), Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. RI Epidemiologicas, Centro de pesquisas /D-4561-2013 NR 43 TC 62 Z9 65 U1 1 U2 16 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 BP 113 EP 118 DI 10.1016/j.ajog.2011.10.865 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 886FA UT WOS:000299836800012 PM 22177186 ER PT J AU Villar, J Papageorghiou, AT Knight, HE Gravett, MG Iams, J Waller, SA Kramer, M Culhane, JF Barros, FC Conde-Agudelo, A Bhutta, ZA Goldenberg, RL AF Villar, Jose Papageorghiou, Aris T. Knight, Hannah E. Gravett, Michael G. Iams, Jay Waller, Sarah A. Kramer, Michael Culhane, Jennifer F. Barros, Fernando C. Conde-Agudelo, Agustin Bhutta, Zulfiqar A. Goldenberg, Robert L. TI The preterm birth syndrome: a prototype phenotypic classification SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material DE phenotype; preterm birth AB Preterm birth is a syndrome with many causes and phenotypes. We propose a classification that is based on clinical phenotypes that are defined by >= 1 characteristics of the mother, the fetus, the placenta, the signs of parturition, and the pathway to delivery. Risk factors and mode of delivery are not included. There are 5 components in a preterm birth phenotype: (1) maternal conditions that are present before presentation for delivery, (2) fetal conditions that are present before presentation for delivery, (3) placental pathologic conditions, (4) signs of the initiation of parturition, and (5) the pathway to delivery. This system does not force any preterm birth into a predefined phenotype and allows all relevant conditions to become part of the phenotype. Needed data can be collected from the medical records to classify every preterm birth. The classification system will improve understanding of the cause and improve surveillance across populations. C1 [Iams, Jay] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Villar, Jose; Papageorghiou, Aris T.; Knight, Hannah E.] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England. [Villar, Jose; Papageorghiou, Aris T.; Knight, Hannah E.] Univ Oxford, Oxford Maternal & Perinatal Hlth Inst, Green Templeton Coll, Oxford, England. Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Gravett, Michael G.; Waller, Sarah A.] Seattle Childrens, Global Alliance Prevent Prematur & Stillbirth, Seattle, WA USA. [Kramer, Michael] McGill Univ, Dept Pediat, Fac Med, Montreal, PQ H3A 2T5, Canada. [Kramer, Michael] McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 2T5, Canada. [Culhane, Jennifer F.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Barros, Fernando C.] Univ Catolica Pelotas, Postgrad Course Hlth & Behav, Pelotas, RS, Brazil. [Conde-Agudelo, Agustin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Conde-Agudelo, Agustin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Bhutta, Zulfiqar A.] Aga Khan Univ, Div Women & Child Hlth, Karachi, Pakistan. [Goldenberg, Robert L.] Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. RP Iams, J (reprint author), Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. EM Jay.Iams@osumc.edu RI Epidemiologicas, Centro de pesquisas /D-4561-2013; Barros, Fernando/D-4857-2013 NR 11 TC 63 Z9 65 U1 0 U2 11 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 BP 119 EP 123 DI 10.1016/j.ajog.2011.10.866 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 886FA UT WOS:000299836800013 PM 22177191 ER PT J AU Esplin, MS AF Esplin, M. Sean TI Proteomic identification of serum peptides predicting subsequent spontaneous preterm birth REPLY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 Univ Utah, Hlth Sci Ctr, Med Units Network, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Salt Lake City, UT 84132 USA. RP Esplin, MS (reprint author), Univ Utah, Hlth Sci Ctr, Med Units Network, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Salt Lake City, UT 84132 USA. EM sean.esplin@imail.org NR 1 TC 1 Z9 1 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2012 VL 206 IS 2 BP E3 EP E4 DI 10.1016/j.ajog.2011.09.011 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 886FA UT WOS:000299836800003 ER PT J AU Romero, R Nicolaides, K Conde-Agudelo, A Tabor, A O'Brien, JM Cetingoz, E Da Fonseca, E Creasy, GW Klein, K Rode, L Soma-Pillay, P Fusey, S Cam, C Alfirevic, Z Hassan, SS AF Romero, Roberto Nicolaides, Kypros Conde-Agudelo, Agustin Tabor, Ann O'Brien, John M. Cetingoz, Elcin Da Fonseca, Eduardo Creasy, George W. Klein, Katharina Rode, Line Soma-Pillay, Priya Fusey, Shalini Cam, Cetin Alfirevic, Zarko Hassan, Sonia S. TI Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE admission to neonatal intensive care unit; birthweight < 1500 g; mechanical ventilation; prematurity; preterm birth; progestin; respiratory distress syndrome; transvaginal ultrasound; uterine cervix; 17 alpha-hydroxyprogesterone caproate ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; GENE-ENVIRONMENT INTERACTION; GROWTH-FACTOR-I; DOUBLE-BLIND; UTERINE CERVIX; 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; RECEPTOR-A; HIGH-RISK; MICRONIZED PROGESTERONE AB OBJECTIVE: To determine whether the use of vaginal progesterone in asymptomatic women with a sonographic short cervix (<= 25 mm) in the midtrimester reduces the risk of preterm birth and improves neonatal morbidity and mortality. STUDY DESIGN: Individual patient data metaanalysis of randomized controlled trials. RESULTS: Five trials of high quality were included with a total of 775 women and 827 infants. Treatment with vaginal progesterone was associated with a significant reduction in the rate of preterm birth <33 weeks (relative risk [RR], 0.58; 95% confidence interval [CI], 0.42-0.80), <35 weeks (RR, 0.69; 95% CI, 0.55-0.88), and <28 weeks (RR, 0.50; 95% CI, 0.30-0.81); respiratory distress syndrome (RR, 0.48; 95% CI, 0.30-0.76); composite neonatal morbidity and mortality (RR, 0.57; 95% CI, 0.40-0.81); birthweight <1500 g (RR, 0.55; 95% CI, 0.38-0.80); admission to neonatal intensive care unit (RR, 0.75; 95% CI, 0.59-0.94); and requirement for mechanical ventilation (RR, 0.66; 95% CI, 0.44-0.98). There were no significant differences between the vaginal progesterone and placebo groups in the rate of adverse maternal events or congenital anomalies. CONCLUSION: Vaginal progesterone administration to asymptomatic women with a sonographic short cervix reduces the risk of preterm birth and neonatal morbidity and mortality. C1 [Romero, Roberto; Conde-Agudelo, Agustin; Hassan, Sonia S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Romero, Roberto; Conde-Agudelo, Agustin; Hassan, Sonia S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Nicolaides, Kypros] Kings Coll Hosp London, Dept Obstet & Gynecol, London, England. [Tabor, Ann; Rode, Line] Rigshosp, Copenhagen Univ Hosp, Dept Fetal Med, DK-2100 Copenhagen, Denmark. [Tabor, Ann] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [O'Brien, John M.] Univ Kentucky, Perinatal Diagnost Ctr, Cent Baptist Hosp, Lexington, KY USA. [O'Brien, John M.] Univ Kentucky, Dept Obstet & Gynecol, Lexington, KY USA. [Cetingoz, Elcin; Cam, Cetin] Zeynep Kamil Women & Children Dis Educ & Res Hosp, Dept Obstet & Gynecol, Istanbul, Turkey. [Da Fonseca, Eduardo] Univ Sao Paulo, Dept Obstet & Ginecol, Hosp Servidor Publ Estadual Francisco Morato Oliv, Sao Paulo, Brazil. [Da Fonseca, Eduardo] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Creasy, George W.] Columbia Labs Inc, Livingston, NJ USA. [Klein, Katharina] Med Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria. [Soma-Pillay, Priya] Steve Biko Acad Hosp, Dept Obstet & Gynecol, Pretoria, South Africa. [Soma-Pillay, Priya] Univ Pretoria, ZA-0002 Pretoria, South Africa. [Fusey, Shalini] Govt Med Coll & Hosp, Dept Obstet & Gynecol, Nagpur, Maharashtra, India. [Alfirevic, Zarko] Univ Liverpool, Dept Womens & Childrens Hlth, Liverpool L69 3BX, Merseyside, England. [Hassan, Sonia S.] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA. RP Romero, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RI Fonseca, Eduardo/A-2490-2013; OI Creasy, George/0000-0002-6645-4238 FU Columbia Laboratories Inc; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services FX The majority of the authors report no conflict of interest except as stated in this paragraph. J.M.O'B. was involved in studies of progesterone gel treatment for preterm birth prevention sponsored by Columbia Laboratories Inc, the manufacturer of the preparation used in the PREGNANT Trial and a previous trial of vaginal progesterone in women at risk for preterm delivery. J.M.O'B. serves on advisory boards and is a consultant for Watson Pharmaceuticals, a company with a financial interest in marketing vaginal progesterone gel for the prevention of preterm birth. He and others are listed in the patent on the use of all progesterone compounds to prevent preterm birth (US Patent No. 7,884,093: Progesterone for the Treatment and Prevention of Spontaneous Preterm Birth). G. W. C. is an employee of Columbia Laboratories Inc.; This research was supported, in part, by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. NR 185 TC 51 Z9 65 U1 0 U2 7 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 124.e1 DI 10.1016/j.ajog.2011.12.003 PG 19 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 886FA UT WOS:000299836800014 PM 22284156 ER PT J AU Horvath, B Mukhopadhyay, P Hasko, G Pacher, P AF Horvath, Bela Mukhopadhyay, Partha Hasko, Gyoergy Pacher, Pal TI The Endocannabinoid System and Plant-Derived Cannabinoids in Diabetes and Diabetic Complications SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Review ID CB1 RECEPTOR ANTAGONIST; OBESE ZUCKER RATS; ENDOPLASMIC-RETICULUM STRESS; RANDOMIZED CONTROLLED-TRIAL; CORONARY-ARTERY-DISEASE; OXIDATIVE STRESS; CELL-DEATH; INSULIN-SECRETION; RISK-FACTORS; CARDIOMETABOLIC RISK AB Oxidative stress and inflammation play critical roles in the development of diabetes and its complications. Recent studies provided compelling evidence that the newly discovered lipid signaling system (ie, the endocannabinoid system) may significantly influence reactive oxygen species production, inflammation, and subsequent tissue injury, in addition to its well-known metabolic effects and functions. The modulation of the activity of this system holds tremendous therapeutic potential in a wide range of diseases, ranging from cancer, pain, neurodegenerative, and cardiovascular diseases to obesity and metabolic syndrome, diabetes, and diabetic complications. This review focuses on the role of the endocannabinoid system in primary diabetes and its effects on various diabetic complications, such as diabetic cardiovascular dysfunction, nephropathy, retinopathy, and neuropathy, particularly highlighting the mechanisms beyond the metabolic consequences of the activation of the endocannabinoid system. The therapeutic potential of targeting the endocannabinoid system and certain plant-derived cannabinoids, such as cannabidiol and Delta 9-tetra-hydrocannabivarin, which are devoid of psychotropic effects and possess potent anti-inflammatory and/or antioxidant properties, in diabetes and diabetic complications is also discussed. (Am J Pathol 2012, 180:432-442; DOI: 10.1016/j.ajpath.2011.11.003) C1 [Horvath, Bela; Mukhopadhyay, Partha; Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Horvath, Bela] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary. [Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM horvathba@mail.nih.gov; pacher@mail.nih.gov RI Horvath, Bela/A-7368-2009; Pacher, Pal/B-6378-2008; MUKHOPADHYAY, PARTHA/G-3890-2010 OI Pacher, Pal/0000-0001-7036-8108; MUKHOPADHYAY, PARTHA/0000-0002-1178-1274 FU National Institute of Alcohol Abuse and Alcoholism, NIH; Hungarian Scientific Research Fund Fellowship [OTKA-NKTH-EU MB08 80238] FX Supported by the Intramural Research Program of the National Institute of Alcohol Abuse and Alcoholism, NIH (P.P.). Dr. Horvath is a recipient of the Hungarian Scientific Research Fund Fellowship (OTKA-NKTH-EU MB08 80238). NR 104 TC 35 Z9 38 U1 0 U2 10 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 432 EP 442 DI 10.1016/j.ajpath.2011.11.003 PG 11 WC Pathology SC Pathology GA 887HZ UT WOS:000299918800001 PM 22155112 ER PT J AU Liu, XF Ory, V Chapman, S Yuan, H Albanese, C Kallakury, B Timofeeva, OA Nealon, C Dakic, A Simic, V Haddad, BR Rhim, JS Dritschilo, A Riegel, A McBride, A Schlegel, R AF Liu, Xuefeng Ory, Virginie Chapman, Sandra Yuan, Hang Albanese, Chris Kallakury, Bhaskar Timofeeva, Olga A. Nealon, Caitlin Dakic, Aleksandra Simic, Vera Haddad, Bassem R. Rhim, Johng S. Dritschilo, Anatoly Riegel, Anna McBride, Alison Schlegel, Richard TI ROCK Inhibitor and Feeder Cells Induce the Conditional Reprogramming of Epithelial Cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PLURIPOTENT STEM-CELLS; HUMAN-PAPILLOMAVIRUS TYPE-16; PRIMARY HUMAN KERATINOCYTES; TELOMERASE ACTIVITY; HTERT PROMOTER; BREAST-CANCER; IN-VITRO; IMMORTALIZATION; SURVIVAL; TRANSFORMATION AB We demonstrate that a Rho kinase inhibitor (Y-27632), in combination with fibroblast feeder cells, induces normal and tumor epithelial cells from many tissues to proliferate indefinitely in vitro, without transduction of exogenous viral or cellular genes. Primary prostate and mammary cells, for example, are reprogrammed toward a basaloid, stem-like phenotype and form well-organized prostaspheres and mammospheres in Matrigel. However, in contrast to the selection of rare stem-like cells, the described growth conditions can generate 2 x 10(6) cells in 5 to 6 days from needle biopsies, and can generate cultures from cryopreserved tissue and from fewer than four viable cells. Continued cell proliferation is dependent on both feeder cells and Y-27632, and the conditionally reprogrammed cells (CRCs) retain a normal karyotype and remain nontumorigenic. This technique also efficiently establishes cell cultures from human and rodent tumors. For example, CRCs established from human prostate adenocarcinoma displayed instability of chromosome 13, proliferated abnormally in Matrigel, and formed tumors in mice with severe combined immunodeficiency. The ability to rapidly generate many tumor cells from small biopsy specimens and frozen tissue provides significant opportunities for cell-based diagnostics and therapeutics (including chemosensitivity testing) and greatly expands the value of biobanking. In addition, the CRC method allows for the genetic manipulation of epithelial cells ex vivo and their subsequent evaluation in vivo in the same host. (Am J Pathol 2012, 180: 599-607; DOI: 10.1016/j.ajpath.2011.10.036) C1 [Liu, Xuefeng; Yuan, Hang; Albanese, Chris; Kallakury, Bhaskar; Nealon, Caitlin; Dakic, Aleksandra; Simic, Vera; Schlegel, Richard] Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Dept Pathol, Washington, DC 20057 USA. [Ory, Virginie; Albanese, Chris; Timofeeva, Olga A.; Haddad, Bassem R.; Dritschilo, Anatoly; Riegel, Anna] Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. [Chapman, Sandra; McBride, Alison] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Rhim, Johng S.] Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA. RP Schlegel, R (reprint author), Georgetown Univ, Med Ctr, Dept Pathol, 3900 Reservoir Rd NW, Washington, DC 20057 USA. EM schleger@georgetown.edu RI Chapman, Sandra/I-8889-2014; OI Chapman, Sandra/0000-0002-9202-336X; McBride, Alison/0000-0001-5607-5157 FU NIH [R01 CA129003, R01 CA113477, R01 CA106400]; Department of Defense [W81XWH-10-1-0747]; NCI CCSG [5P30CA051008]; National Institute of Allergy and Infectious Diseases FX Supported by NIH grants R01 CA129003 (C.A.), R01 CA113477 (A.R.), and R01 CA106400 (R.S.); a Department of Defense fellowship (W81XWH-10-1-0747 to V.O.); and two internal development grants (NCI CCSG 5P30CA051008 to X.L. and A.R., respectively). This work was funded, in part, by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the NIH. NR 54 TC 179 Z9 181 U1 6 U2 38 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 599 EP 607 DI 10.1016/j.ajpath.2011.10.036 PG 9 WC Pathology SC Pathology GA 887HZ UT WOS:000299918800016 PM 22189618 ER PT J AU Robinson, OJ Cools, R Carlisi, CO Sahakian, BJ Drevets, WC AF Robinson, Oliver J. Cools, Roshan Carlisi, Christina O. Sahakian, Barbara J. Drevets, Wayne C. TI Ventral Striatum Response During Reward and Punishment Reversal Learning in Unmedicated Major Depressive Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID INDUCED DOPAMINE RELEASE; PARKINSONS-DISEASE; BASAL GANGLIA; NEURAL BASIS; FEEDBACK; MECHANISMS; PREDICTION; DEPLETION; VALENCE; BRAIN AB Objective: Affective biases may underlie many of the key symptoms of major depressive disorder, from anhedonia to altered cognitive performance. Understanding the cause of these biases is therefore critical in the quest for improved treatments. Depression is associated, for example, with a negative affective bias in reversal learning. However, despite the fact that reversal learning is associated with striatal response in healthy individuals and depressed individuals exhibit attenuated striatal function on multiple tasks, studies to date have not demonstrated striatal involvement in the negative bias in reversal learning in depression. In this study, the authors sought to determine whether this may be because reversal learning tasks conventionally used to study behavior examine reversals only on the basis of unexpected punishment and therefore do not adequately separate reward- and punishment-based behavior. Method: The authors used functional MRI to compare the hemodynamic response to a reversal learning task with mixed reward- and punishment-based reversal stages between individuals with unmedicated major depressive disorder (N=13) and healthy comparison subjects (N=14). Results: Impaired reward (but not punishment) reversal accuracy was found alongside attenuated anteroventral striatal response to unexpected reward in depression. Conclusions: Attenuated neurophysiological response of the anteroventral striatum may reflect dysfunction in circuits involving afferent projections from the orbitofrontal, limbic, and/or mesostriatal dopaminergic pathways, which conceivably may, together with the ventral striatum, underlie anhedonia in depression. Learning to appreciate and enjoy positive life experiences is critical for recovery from depression. This study pinpoints a neural target for such recovery. C1 [Robinson, Oliver J.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. Univ Cambridge, Dept Psychiat, Cambridge, England. Univ Cambridge, MRC Wellcome Trust Behav & Clin Neurosci Inst, Cambridge, England. Addenbrookes Hosp, Cambridge, England. Radboud Univ Nijmegen, Med Ctr, Ctr Cognit Neuroimaging, Donders Inst Brain Cognit & Behav,Dept Psychiat, NL-6525 ED Nijmegen, Netherlands. Univ Oklahoma, Coll Med, Laureate Inst Brain Res, Tulsa, OK USA. Univ Oklahoma, Coll Med, Dept Psychiat, Tulsa, OK USA. RP Robinson, OJ (reprint author), NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. EM oliver.j.robinson@gmail.com RI Robinson, Oliver/B-3646-2011; Cools, Roshan/D-1905-2010; OI Robinson, Oliver/0000-0002-3100-1132; Carlisi, Christina/0000-0002-0942-8586 FU Johnson Johnson; NIMH [04-M-0002] FX Dr. Sahakian has received grant support from Johnson & Johnson, has served as a consultant for Boehringer-Ingelheim, Cambridge Cognition, Eli Lilly, GlaxoSmithKline, Hoffmann-La Roche, Novartis, and Shire, and receives an honorarium from the Journal of Psychological Medicine, Dr. Drevets has served as a consultant for Pfizer, Johnson & Johnson, Eisai, and Rules-Based Medicine. The other authors report no financial relationships with commercial interests.; Supported by the NIMH Intramural Research Program (protocol number 04-M-0002). NR 40 TC 70 Z9 72 U1 1 U2 29 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 152 EP 159 DI 10.1176/appi.ajp.2011.11010137 PG 8 WC Psychiatry SC Psychiatry GA 890BW UT WOS:000300121100010 PM 22420038 ER PT J AU Vitiello, B Elliott, GR Swanson, JM Arnold, LE Hechtman, L Abikoff, H Molina, BSG Wells, K Wigal, T Jensen, PS Greenhill, LL Kaltman, JR Severe, JB Odbert, C Hur, K Gibbons, R AF Vitiello, Benedetto Elliott, Glen R. Swanson, James M. Arnold, L. Eugene Hechtman, Lily Abikoff, Howard Molina, Brooke S. G. Wells, Karen Wigal, Timothy Jensen, Peter S. Greenhill, Laurence L. Kaltman, Jonathan R. Severe, Joanne B. Odbert, Carol Hur, Kwan Gibbons, Robert TI Blood Pressure and Heart Rate Over 10 Years in the Multimodal Treatment Study of Children With ADHD SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; SALTS EXTENDED-RELEASE; SCHOOL-AGED CHILDREN; FOLLOW-UP; SUDDEN-DEATH; VENTRICULAR TACHYARRHYTHMIAS; OROS METHYLPHENIDATE; TREATMENT STRATEGIES; NATIONAL-INSTITUTE; SHORT-TERM AB Objective: It is unknown whether prolonged childhood exposure to stimulant medication for the treatment of attention deficit hyperactivity disorder (ADHD) increases the risk for developing abnormalities in blood pressure or heart rate. The authors examined the association between stimulant medication and blood pressure and heart rate over 10 years. Method: A total of 579 children, ages 7-9, were randomly assigned to 14 months of medication treatment, behavioral therapy, the combination of the two, or usual community treatment. The controlled trial was followed by naturalistic treatment with periodic assessments. Blood pressure and heart rate data were first analyzed with linear regression models based on an intent-to-treat approach, using raw data and the blood pressure categories of prehypertension and hypertension. Currently medicated patients were then compared with never or previously medicated patients. Associations between cumulative stimulant exposure and blood pressure or heart rate were assessed. Results: No treatment effect on either systolic or diastolic blood pressure could be detected. Children who were treated with stimulants had a higher heart rate (mean=84.2 bpm [SD=12.4] on medication alone and mean=84.6 bpm [SD=12.2] on medication plus behavioral therapy) than those who were treated with behavioral therapy alone (mean=79.1 bpm [SD=12.0]) or those who received usual community treatment (mean=78.9 bpm [SD=12.9]) at the end of the 14-month controlled trial, but not thereafter. Stimulant medication did not increase the risk for tachycardia, but greater cumulative stimulant exposure was associated with a higher heart rate at years 3 and 8. Conclusions: Stimulant treatment did not increase the risk for prehypertension or hypertension over the 10-year period of observation. However, stimulants had a persistent adrenergic effect on heart rate during treatment. C1 [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. Childrens Hlth Council, Dept Psychiat, Palo Alto, CA USA. Univ Calif Irvine, Child Dev Ctr, Irvine, CA USA. Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA. McGill Univ, Dept Psychiat, Montreal, PQ, Canada. NYU, Dept Child & Adolescent Psychiat, New York, NY 10003 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Duke Univ, Med Ctr, Family Studies Clin, Durham, NC USA. REACH Inst, New York, NY USA. Columbia Univ, Res Unit Pediat Psychopharmacol, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. Univ Illinois, Ctr Hlth Stat, Chicago, IL USA. Univ Chicago, Ctr Hlth Stat, Chicago, IL 60637 USA. RP Vitiello, B (reprint author), NIMH, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov OI Jensen, Peter/0000-0003-2387-0650 FU AstraZeneca; CureMark; Lilly; Neuropharm; Novartis; Organon; Shire; Targacept; Eli Lilly; GlaxoSmithKline; Ortho-Janssen; Purdue; Bristol-Myers-Squibb; Celltech; Cephalon; McNeil; Pfizer; Multi-Health Systems; Addernex; Otsuka; Shionogi; Janssen-Ortho; Johnson Johnson; Rhodes Pharmaceutical; NIMH [U01MH50461, N01MH12009, HHSN271200800005-C]; Duke University [U01MH50477, N01MH12012, HHSN271200800009-C]; University of California, Irvine [U01MH50440, N01 MH12011, HH-SN271200800006-C]; Research Foundation for Mental Hygiene-New York State Psychiatric Institute/Columbia University [U01MH50467, N01 MH12007, HHSN271200800007-C]; Long Island Jewish Medical Center [U01MH50453]; New York University [N01 MH12004, HHSN271200800004-C]; University of Pittsburgh [U01MH50467, N01 MH12010, HHSN271200800008-C]; McGill University [N01 MH12008, HHSN271200800003-C] FX Dr. Elliott has received investigator-initiated research support from BioMarin Pharmaceuticals. Dr Swanson has received research support from Alza, Celgene, Cephalon, ICB, McNeil, Novartis, and Shire. Dr. Arnold has received research funding or consulting, advisory, or speaking fees from AstraZeneca, CureMark, Lilly, Neuropharm, Novartis, Organon, Shire, and Targacept. Dr. Hechtman has received research support or advisory or speaking fees from Eli Lilly, GlaxoSmithKline, Ortho-Janssen, Purdue, and Shire. Dr. Abikoff has received research funding or consulting or speaking fees from Bristol-Myers-Squibb, Celltech, Cephalon, Eli Lilly, McNeil, Novartis, Pfizer, and Shire. Dr. Wells receives royalty income from Multi-Health Systems and conducts workshop training in psychosocial treatments for the REACH Institute and the State of New York. Dr. Wigal has received research support or consulting or speaking fees from Addernex, Eli Lilly, McNeil, Otsuka, Shionogi, and Shire. Dr. Jensen has received advisory board or speaking fees from Janssen-Ortho and Shire. Dr. Greenhill has received research support from Johnson & Johnson, Rhodes Pharmaceutical, and Shire. The other authors report no financial relationships with commercial interests.; Supported by cooperative agreement grants and contracts from NIMH to the University of California, Berkeley (U01MH50461, N01MH12009, and HHSN271200800005-C), Duke University (U01MH50477, N01MH12012, and HHSN271200800009-C), University of California, Irvine (U01MHSO440, N01 MH12011, and HH-SN271200800006-C), Research Foundation for Mental Hygiene-New York State Psychiatric Institute/Columbia University (U01MHSO467, N01 MH12007, and HHSN271200800007-C), Long Island Jewish Medical Center (U01MH50453), New York University (N01 MH12004 and HHSN271200800004-C), University of Pittsburgh (U01MHSO467, N01 MH12010, and HHSN271200800008-C), and McGill University (N01 MH12008 and HHSN271200800003-C). Statistical analysis was funded by a professional contract to the Center for Health Statistics, University of Illinois at Chicago. NR 39 TC 35 Z9 35 U1 2 U2 17 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 167 EP 177 DI 10.1176/appi.ajp.2011.10111705 PG 11 WC Psychiatry SC Psychiatry GA 890BW UT WOS:000300121100012 PM 21890793 ER PT J AU Guyer, AE Choate, VR Detloff, A Benson, B Nelson, EE Perez-Edgar, K Fox, NA Pine, DS Ernst, M AF Guyer, Amanda E. Choate, Victoria R. Detloff, Allison Benson, Brenda Nelson, Eric E. Perez-Edgar, Koraly Fox, Nathan A. Pine, Daniel S. Ernst, Monique TI Striatal Functional Alteration During Incentive Anticipation in Pediatric Anxiety Disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; SOCIAL ANXIETY; BEHAVIORAL-INHIBITION; FEARFUL FACES; YOUNG-ADULTS; ADOLESCENTS; AMYGDALA; CHILDREN; RISK; REWARD AB Objective: Behavioral inhibition is an early childhood temperament recently associated with altered striatal response in adolescence to incentives of increasing magnitudes. Since early childhood behavioral inhibition is also associated with risk for adolescent social phobia, a similar pattern of striatal activation may manifest in social phobia. The present study compares striatal function in healthy adolescents, adolescents with social phobia, and adolescents with generalized anxiety disorder. Method: Blood-oxygen-level-dependent signal in striatal regions was examined in 58 medication-free adolescents-14 with social phobia, 18 with generalized anxiety disorder but not social phobia, and 26 with no psychiatric disorder matched on sex, age, puberty, IQ, and socioeconomic status. During functional magnetic resonance imaging, participants responded to incentive cues depicting potential monetary gains or losses of varying magnitudes. Results: While anticipating incentives of increasing magnitude, adolescents with social phobia showed increasingly heightened caudate and putamen activation at a level greater than that seen in the healthy comparison and generalized anxiety disorder groups. The generalized anxiety disorder group showed a unique valence-specific putamen response relative to the healthy comparison or social phobia group. Both patient groups displayed more complex patterns in the nucleus accumbens than in the caudate or putamen. Conclusions: Caudate and putamen hypersensitivity to incentives of increasing magnitudes characterizes adolescent social phobia, relative to activation in this region in adolescents with generalized anxiety disorder as well as healthy adolescents. Thus, these findings resemble the pattern previously found in adolescents with early childhood behavioral inhibition, thereby implicating similar neural responses to anticipation of incentives in both early childhood behavioral inhibition and adolescent social phobia. C1 [Guyer, Amanda E.] Univ Calif Davis, Dept Human & Community Dev, Ctr Mind & Brain, Davis, CA 95616 USA. NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. RP Guyer, AE (reprint author), Univ Calif Davis, Dept Human & Community Dev, Ctr Mind & Brain, Davis, CA 95616 USA. EM aeguyer@ucdavis.edu RI Nelson, Eric/B-8980-2008; OI Nelson, Eric/0000-0002-3376-2453; Perez-Edgar, Koraly/0000-0003-4051-9563 FU National Institute of Mental Health; National Institutes of Health [K99/R00 MH-080076] FX Supported by the Intramural Research Program of the National Institute of Mental Health and a National Institutes of Health Career Development Award (K99/R00 MH-080076) (Dr. Guyer). NR 40 TC 56 Z9 57 U1 4 U2 9 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 205 EP 212 DI 10.1176/appi.ajp.2011.11010006 PG 8 WC Psychiatry SC Psychiatry GA 890BW UT WOS:000300121100016 PM 22423352 ER PT J AU Arrigo, NC Briese, T Calisher, CH Drebot, MA Fljelle, B LeDuc, JW Powers, AM Repik, PM Roehrig, JT Schmaljohn, CS Tesh, RB Weaver, SC AF Arrigo, Nicole C. Briese, Thomas Calisher, Charles H. Drebot, Michael A. Fljelle, Brian LeDuc, James W. Powers, Ann M. Repik, Patricia M. Roehrig, John T. Schmaljohn, Connie S. Tesh, Robert B. Weaver, Scott C. TI Recommendations for Publication of Viral Genetic Data and Sample Access for Novel Viruses and Strains SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID DEPENDENT DNA POLYMERASE; VIRIONS C1 [LeDuc, James W.; Tesh, Robert B.; Weaver, Scott C.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Arrigo, Nicole C.; Briese, Thomas] Columbia Univ, Ctr Infect & Immun, Mailman Sch Publ Hlth, New York, NY USA. [Calisher, Charles H.] Colorado State Univ, Arthropod Borne & Infect Dis Lab, Dept Microbiol Immunol & Pathol, Coll Vet Med & Biomed Sci, Ft Collins, CO 80523 USA. [Drebot, Michael A.] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada. [Fljelle, Brian] Univ New Mexico, Sch Med, Infect Dis & Inflammat Program, Dept Pathol Biol & Mol Genet, Albuquerque, NM 87131 USA. [Fljelle, Brian] Univ New Mexico, Sch Med, Infect Dis & Inflammat Program, Dept Microbiol, Albuquerque, NM 87131 USA. [Powers, Ann M.; Roehrig, John T.] Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Vector Borne Infect Dis, Ft Collins, CO USA. [Repik, Patricia M.] NIAID, Virol Branch, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. [Schmaljohn, Connie S.] USA, Med Res Inst Infect Dis, Dept Mol Virol, Div Virol, Frederick, MD USA. RP Weaver, SC (reprint author), Univ Texas Med Branch, Inst Human Infect & Immun, 301 Univ Blvd, Galveston, TX 77555 USA. EM ncarrigo@gmail.com; thomas.briese@columbia.edu; calisher@cybersafe.net; Mike_Drebot@hc-sc.gc.ca; bhjelle@salud.unm.edu; jwleduc@UTMB.EDU; AKP7@cdc.gov; prepik@niaid.nih.gov; trl@CDC.GOV; connie.schmaljohn@us.army.mil; rtesh@utmb.edu; sweaver@utmb.edu RI Weaver, Scott/D-6490-2011; OI Roehrig, John/0000-0001-7581-0479 NR 5 TC 2 Z9 2 U1 0 U2 0 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 189 EP 191 DI 10.4269/ajtmh.2012.11-0523 PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 886PQ UT WOS:000299866700002 PM 22302845 ER PT J AU Chaube, R Kallakunta, VM Espey, MG McLarty, R Faccenda, A Ananvoranich, S Mutus, B AF Chaube, Ruchi Kallakunta, Vasantha Madhuri Espey, Michael Graham McLarty, Ryan Faccenda, Adam Ananvoranich, Sirinart Mutus, Bulent TI Endoplasmic reticulum stress-mediated inhibition of NSMase2 elevates plasma membrane cholesterol and attenuates NO production in endothelial cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE Neutral sphingomyelinase 2; Nitric oxide synthase; Nitric oxide; ER stress; Endothelial dysfunction ID NITRIC-OXIDE SYNTHASE; ELEMENT-BINDING PROTEINS; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE-CELLS; OXIDATIVE STRESS; NEUTRAL SPHINGOMYELINASE; ENOS ACTIVITY; ACTIVATION; DYSFUNCTION; APOPTOSIS AB Chronic exposure of blood vessels to cardiovascular risk factors such as free fatty acids, LDL-cholesterol, homocysteine and hyperglycemia can give rise to endothelial dysfunction, partially due to decreased synthesis and bioavailability of nitric oxide (NO). Many of these same risk factors have been shown to induce endoplasmic reticulum (ER) stress in endothelial cells. The objective of this study was to examine the mechanisms responsible for endothelial dysfunction mediated by ER stress. ER stress elevated both intracellular and plasma membrane (PM) cholesterols in BAEC by similar to 3-fold, indicated by epifluorescence and cholesterol oxidase methods. Increases in cholesterol levels inversely correlated with neutral sphingomyelinase 2 (NSMase2) activity, endothelial nitric oxide synthase (eNOS) phospho-activation and NO-production. To confirm that ER stress-induced effects on PM cholesterol were a direct consequence of decreased NSMase2 activity, enzyme expression was either enhanced or knocked down in BAEC. NSMase2 over-expression did not significantly affect cholesterol levels or NO-production, but increased eNOS phosphorylation by similar to 1.7-fold. Molecular knock down of NSMase2 decreased eNOS phosphorylation and NO-production by 50% and 40%, respectively while increasing PM cholesterol by 1.7-fold and intracellular cholesterol by 2.7-fold. Furthermore, overexpression of NSMase2 in ER-stressed BAEC lowered cholesterol levels to within control levels as well as nearly doubled the NO production, restoring it to similar to 74% and 68% of controls using tunicamycin and palmitate, respectively. This study establishes NSMase2 as a pivotal enzyme in the onset of endothelial ER stress-mediated vascular dysfunction as its inactivation leads to the attenuation of NO production and the elevation of cellular cholesterol. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved. C1 [Chaube, Ruchi; Kallakunta, Vasantha Madhuri; McLarty, Ryan; Faccenda, Adam; Ananvoranich, Sirinart; Mutus, Bulent] Univ Windsor, Dept Chem & Biochem, Windsor, ON N9B 3P4, Canada. [Espey, Michael Graham] NIDDK, Mol & Clin Nutr Sect, Natl Inst Hlth Bethesda, Bethesda, MD 20892 USA. RP Mutus, B (reprint author), Univ Windsor, Dept Chem & Biochem, Windsor, ON N9B 3P4, Canada. EM mutusb@uwindsor.ca FU Natural Sciences and Engineering Research Council of Canada (NSERC); University of Windsor FX This study was supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) and funds from the University of Windsor Research Chair Program to BM. NR 52 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD FEB PY 2012 VL 1821 IS 2 BP 313 EP 323 DI 10.1016/j.bbalip.2011.10.015 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 889KP UT WOS:000300072900008 PM 22063270 ER PT J AU Wu, T Fallin, MD Shi, M Ruczinski, I Liang, KY Hetmanski, JB Wang, H Ingersoll, RG Huang, SZ Ye, XQ Wu-Chou, YH Chen, PK Jabs, EW Shi, B Redett, R Scott, AF Murray, JC Marazita, ML Munger, RG Beaty, TH AF Wu, Tao Fallin, M. Daniele Shi, Min Ruczinski, Ingo Liang, Kung Yee Hetmanski, Jacqueline B. Wang, Hong Ingersoll, Roxann G. Huang, Shangzhi Ye, Xiaoqian Wu-Chou, Yah-Huei Chen, Philip K. Jabs, Ethylin Wang Shi, Bing Redett, Richard Scott, Alan F. Murray, Jeffrey C. Marazita, Mary L. Munger, Ronald G. Beaty, Terri H. TI Evidence of gene-environment interaction for the RUNX2 gene and environmental tobacco smoke in controlling the risk of cleft lip with/without cleft palate SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE RUNX2; oral clefts; gene-environment interaction; parent-of-origin effects; imprinting ID LOG-LINEAR APPROACH; FAMILY-BASED TESTS; PARENT-TRIAD DATA; CLEIDOCRANIAL DYSPLASIA; LINKAGE DISEQUILIBRIUM; BIRTH-DEFECTS; ORAL CLEFTS; OROFACIAL CLEFTS; UNIFIED APPROACH; ASSOCIATION AB This study examined the association between 49 markers in the Runt-related transcription factor 2 (RUNX2) gene and nonsyndromic cleft lip with/without cleft palate (CL/P) among 326 Chinese case-parent trios, while considering gene-environment (GxE) interaction and parent-of-origin effects. Five single-nucleotide polymorphisms (SNPs) showed significant evidence of linkage and association with CL/P and these results were replicated in an independent European sample of 825 case-parent trios. We also report compelling evidence for interaction between markers in RUNX2 and environmental tobacco smoke (ETS). Although most marginal SNP effects (i.e., ignoring maternal exposures) were not statistically significant, eight SNPs were significant when considering possible interaction with ETS when testing for gene (G) and GxE interaction simultaneously or when considering GxE alone. Independent samples from European populations showed consistent evidence of significant GxETS interaction at two SNPs (rs6904353 and rs7748231). Our results suggest genetic variation in RUNX2 may influence susceptibility to CL/P through interacting with ETS. Birth Defects Research (Part A) 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Wu, Tao; Fallin, M. Daniele; Ruczinski, Ingo; Liang, Kung Yee; Hetmanski, Jacqueline B.; Ingersoll, Roxann G.; Beaty, Terri H.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Wu, Tao; Wang, Hong] Peking Univ, Sch Publ Hlth, Beijing 100871, Peoples R China. [Shi, Min] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Ingersoll, Roxann G.; Jabs, Ethylin Wang; Redett, Richard; Scott, Alan F.] Johns Hopkins Sch Med, Baltimore, MD USA. [Huang, Shangzhi] Peking Union Med Coll, Beijing 100021, Peoples R China. [Ye, Xiaoqian; Jabs, Ethylin Wang] Mt Sinai Sch Med, New York, NY USA. [Ye, Xiaoqian] Wuhan Univ, Key Lab Oral Biomed Engn, Minist Educ, Hosp Stomatol, Wuhan 430072, Peoples R China. [Ye, Xiaoqian] Wuhan Univ, Key Lab Oral Biomed Engn, Minist Educ, Sch Stomatol, Wuhan 430072, Peoples R China. [Wu-Chou, Yah-Huei; Chen, Philip K.] Chang Gung Mem Hosp, Tao Yuan, Taiwan. [Shi, Bing] Sichuan Univ, W China Coll Stomatol, Chengdu, Sichuan, Peoples R China. [Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Pittsburgh, PA USA. [Munger, Ronald G.] Utah State Univ, Logan, UT 84322 USA. RP Beaty, TH (reprint author), Johns Hopkins Univ, Dept Epidemiol, Sch Publ Hlth, 615 N Wolfe St, Baltimore, MD 21205 USA. EM tbeaty@jhsph.edu OI Jabs, Ethylin/0000-0001-8983-5466 FU National Institute of Dental & Craniofacial Research [R21-DE-013707, R01-DE-014581]; National Institute for Dental and Craniofacial Research [U01-DE-004425]; NIH, National Institute of Environmental Health Sciences FX We thank all of the families at each recruitment site for participating in this study, and we gratefully acknowledge the invaluable assistance of clinical, field, and laboratory staff who contributed to making this work possible. This research was supported by R21-DE-013707 and R01-DE-014581 from the National Institute of Dental & Craniofacial Research. The International Cleft Consortium including genotyping and analysis was supported by the National Institute for Dental and Craniofacial Research through U01-DE-004425; "International Consortium to Identify Genes & Interactions Controlling Oral Clefts", 2007 to 2009; T. H. Beaty, Principal Investigator. Tao Wu is supported by the International Collaborative Genetics Research Training Program (ICGRTP), NIH D43 TW06176. This research was also supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We thank the Smile Train Foundation for supporting cleft research in China. We are particularly grateful to Dr. Jae Woong Sull for his assistance in performing the analyses using LEM. NR 52 TC 6 Z9 7 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD FEB PY 2012 VL 94 IS 2 BP 76 EP 83 DI 10.1002/bdra.22885 PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 888JE UT WOS:000299999000002 PM 22241686 ER PT J AU Jahnke, GD AF Jahnke, Gloria D. TI Summary of the public affairs committee symposium at the teratology society 2011 annual meeting: The thyroid and iodine: Impacts on pregnancy and child health SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Editorial Material C1 [Jahnke, Gloria D.] Natl Inst Environm Hlth Serv, Natl Toxicol Program, Res Triangle Pk, NC USA. RP Jahnke, GD (reprint author), NIEHS MD K2-14,POB 12233,Alexander Dr, Res Triangle Pk, NC 27709 USA. EM jahnke@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD FEB PY 2012 VL 94 IS 2 BP 114 EP 115 DI 10.1002/bdra.22880 PG 2 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 888JE UT WOS:000299999000007 ER PT J AU Loeb, S Metter, EJ Kan, DH Roehl, KA Catalona, WJ AF Loeb, Stacy Metter, E. Jeffrey Kan, Donghui Roehl, Kimberly A. Catalona, William J. TI Prostate-specific antigen velocity (PSAV) risk count improves the specificity of screening for clinically significant prostate cancer SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; PSA velocity; risk count; screening; PSA ID RADICAL PROSTATECTOMY; UNITED-STATES; MEN; LIFE; CURABILITY; MORTALITY; THERAPY; WINDOW; CURVE; DEATH AB OBJECTIVE To determine whether the prostate-specific antigen velocity (PSAV) risk count (i.e. the number of times PSAV exceeds a specific threshold) could increase the specificity of screening for prostate cancer and potentially life-threatening tumours. PATIENTS AND METHODS From 1989 to 2001, we calculated two serial PSAV measurements in 18 214 prostate cancer screening-study participants, of whom 1125 (6.2%) were diagnosed with prostate cancer. The PSAV risk count was determined as the number of PSAV measurements of > 0.4 ng/mL/year (0, 1, or 2). We used receiver operating characteristic (ROC) and reclassification analyses to examine the ability of PSAV risk count to predict screen-detected and high-grade prostate cancer. RESULTS The PSAV was > 0.4 ng/mL/year twice (risk count 2) in 40% of prostate cancer cases compared with only 4% of those with no cancer (P < 0.001). After adjusting for age and PSA level, a PSAV risk count of 2 was associated with an 8.2-fold increased risk of prostate cancer (95% confidence interval 7.0-9.6, P < 0.001) and 5.4-fold increased risk of Gleason score 8-10 prostate cancer on biopsy. Compared with a model with age and PSA level, the addition of the PSAV risk count significantly improved discrimination (area under the ROC curve 0.625 vs 0.725, P = 0.031) and reclassified individuals for the risk of high-grade prostate cancer (net reclassification, P < 0.001). CONCLUSIONS Sustained rises in PSA indicate a significantly greater risk of prostate cancer, particularly high-grade disease. Compared with men with a risk count of = 1, those with two PSAV measurements of > 0.4 ng/mL/year (risk count 2) had an 8-fold increased risk of prostate cancer and 5.4-fold increased risk of Gleason 8-10 disease on biopsy, adjusting for age and PSA level. Compared to PSA alone, PSAV risk count may be useful in reducing unnecessary biopsies and the diagnosis of low-risk prostate cancer. C1 [Loeb, Stacy] NYU, Sch Med, Dept Urol, New York, NY 10003 USA. [Metter, E. Jeffrey] NIA, Baltimore, MD 21224 USA. [Kan, Donghui; Catalona, William J.] NW Feinberg Sch Med, Dept Urol, Chicago, IL USA. [Roehl, Kimberly A.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. RP Catalona, WJ (reprint author), 675 N St Clair St,Suite 20-150, Chicago, IL 60611 USA. EM wcatalona@nmff.org OI Loeb, Stacy/0000-0003-3933-9207 FU Urological Research Foundation; Prostate SPORE [P50 CA90386-05S2]; Robert H. Lurie Comprehensive Cancer Center [P30 CA60553]; National Institute of Health, National Institute on Aging FX The research of W.J.C. is supported in part by the Urological Research Foundation, Prostate SPORE grant (P50 CA90386-05S2) and the Robert H. Lurie Comprehensive Cancer Center grant (P30 CA60553). E Jeffery Metter is supported by the Intramural Research Program of the National Institute of Health, National Institute on Aging. NR 27 TC 31 Z9 31 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD FEB PY 2012 VL 109 IS 4 BP 508 EP 513 DI 10.1111/j.1464-410X.2011.10900.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 887QY UT WOS:000299945100007 PM 22296334 ER PT J AU Vaught, JB Henderson, MK Compton, CC AF Vaught, Jimmie B. Henderson, Marianne K. Compton, Carolyn C. TI Biospecimens and Biorepositories: From Afterthought to Science SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID CANCER; GENOME; ART; DNA AB Biospecimens are recognized as critical components of biomedical research, from basic studies to clinical trials and epidemiologic investigations. Biorepositories have existed in various forms for more than 150 years, from early small collections in pathology laboratories to modern automated facilities managing millions of samples. As collaborative science has developed, it has been recognized that biospecimens must be of consistent quality. Recent years have seen a proliferation of best practices and the recognition of the field of "biospecimen science." The future of this field will depend on the development of more evidence-based practices in both the research and clinical settings. As the field matures, educating a new generation of biospecimen/biobanking scientists will be an important need. Cancer Epidemiol Biomarkers Prey; 21(2); 253-5. (C)2012 AACR. C1 [Vaught, Jimmie B.; Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA. [Henderson, Marianne K.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Vaught, JB (reprint author), NCI, Off Biorepositories & Biospecimen Res, NIH, 11400 Rockville Pike,Rockwall 1,Suite 700, Bethesda, MD 20892 USA. EM vaughtj@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 27 TC 25 Z9 26 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2012 VL 21 IS 2 BP 253 EP 255 DI 10.1158/1055-9965.EPI-11-1179 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 889KT UT WOS:000300073300001 PM 22313938 ER PT J AU Yassin, R Weil, C Lockhart, N AF Yassin, Rihab Weil, Carol Lockhart, Nicole TI Sharing Individual Research Results with Biospecimen Contributors: Point SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PARTICIPANTS C1 [Weil, Carol; Lockhart, Nicole] NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA. [Yassin, Rihab] NCI, Div Canc Biol, NIH, Bethesda, MD 20892 USA. RP Yassin, R (reprint author), NCI, Div Canc Biol, 6130 Execut Blvd,Suite 5000, Rockville, MD 20852 USA. EM ry38k@nih.gov; Carol.Weil@nih.gov FU National Cancer Institute FX This work was supported by general appropriations to the National Cancer Institute. NR 13 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2012 VL 21 IS 2 BP 256 EP 259 DI 10.1158/1055-9965.EPI-11-0853 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 889KT UT WOS:000300073300002 PM 22313939 ER PT J AU Stott-Miller, M Chen, C Chuang, SC Lee, YCA Boccia, S Brenner, H Cadoni, G Dal Maso, L La Vecchia, C Lazarus, P Levi, F Matsuo, K Morgenstern, H Muller, H Muscat, J Olshan, AF Purdue, MP Serraino, D Vaughan, TL Zhang, ZF Boffetta, P Hashibe, M Schwartz, SM AF Stott-Miller, Marni Chen, Chu Chuang, Shu-Chun Lee, Yuan-Chin Amy Boccia, Stefania Brenner, Hermann Cadoni, Gabriela Dal Maso, Luigino La Vecchia, Carlo Lazarus, Philip Levi, Fabio Matsuo, Keitaro Morgenstern, Hal Mueller, Heiko Muscat, Joshua Olshan, Andrew F. Purdue, Mark P. Serraino, Diego Vaughan, Thomas L. Zhang, Zuo-Feng Boffetta, Paolo Hashibe, Mia Schwartz, Stephen M. TI History of Diabetes and Risk of Head and Neck Cancer: A Pooled Analysis from the International Head and Neck Cancer Epidemiology Consortium SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS INFECTION; UPPER AERODIGESTIVE TRACT; BODY-MASS INDEX; ORAL-CAVITY; MOLECULAR-MECHANISMS; INHANCE CONSORTIUM; BLOOD-GLUCOSE; MELLITUS; INSULIN AB Background: A history of diabetes is associated with an increased risk of several types of cancers. Whether diabetes is a risk factor for head and neck cancer (HNC) has received little attention. Methods: We pooled data from 12 case control studies including 6,448 cases and 13,747 controls, and estimated OR and 95% CI for the associations between diabetes and HNC, adjusted for age, education level, sex, race/ethnicity, study center, cigarette smoking, alcohol use, and body mass index. Results: We observed a weak association between diabetes and the incidence of HNC overall (OR, 1.09; 95% CI: 0.95-1.24). However, we observed a modest association among never smokers (OR, 1.59; 95% CI: 1.22-2.07), and no association among ever smokers (OR, 0.96; 95% CI: 0.83-1.11); likelihood ratio test for interaction P = 0.001 Conclusion: A history of diabetes was weakly associated with HNC overall, but we observed evidence of effect modification by smoking status, with a positive association among those who never smoked cigarettes. Impact: This study suggests that glucose metabolism abnormalities may be a HNC risk factor in subgroups of the population. Prospective studies incorporating biomarkers are needed to improve our understanding of the relationship between diabetes and HNC risk, possibly providing new strategies in the prevention of HNC. Cancer Epidemiol Biomarkers Prey; 21(2); 294-304. (C)2011 AACR. C1 [Stott-Miller, Marni; Chen, Chu; Vaughan, Thomas L.; Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Stott-Miller, Marni; Chen, Chu; Vaughan, Thomas L.; Schwartz, Stephen M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Chuang, Shu-Chun] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England. [Lee, Yuan-Chin Amy; Hashibe, Mia] Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84112 USA. [Boccia, Stefania; Cadoni, Gabriela] Univ Cattolica Sacro Cuore, Inst Hyg, Rome, Italy. [Brenner, Hermann; Mueller, Heiko] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Dal Maso, Luigino; Serraino, Diego] Ctr Riferimento Oncol, I-33081 Aviano, PN, Italy. [La Vecchia, Carlo] Ist Ric Farmacol Mario Negri, Milan, Italy. [La Vecchia, Carlo] Univ Milan, Milan, Italy. [Lazarus, Philip; Muscat, Joshua] Penn State Coll Med, Hershey, PA USA. [Levi, Fabio] Univ Lausanne, Inst Med Sociale & Prevent, Lausanne, Switzerland. [Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Nagoya, Aichi 464, Japan. [Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol & Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Olshan, Andrew F.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Purdue, Mark P.] NCI, Bethesda, MD 20892 USA. [Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. RP Schwartz, SM (reprint author), Fred Hutchinson Canc Res Ctr, Mailstop M4-C308,1100 Fairview Ave N, Seattle, WA 98109 USA. EM sschwart@fhcrc.org RI Chuang, Shu-Chun/N-3358-2013; Purdue, Mark/C-9228-2016; Brenner, Hermann/B-4627-2017; OI Purdue, Mark/0000-0003-1177-3108; Brenner, Hermann/0000-0002-6129-1572; dal maso, luigino/0000-0001-6163-200X; Serraino, Diego/0000-0003-0565-8920; La Vecchia, Carlo/0000-0003-1441-897X; Schwartz, Stephen/0000-0001-7499-8502; Matsuo, Keitaro/0000-0003-1761-6314 FU INHANCE [NCI R03CA113157]; Italian Association for Research on Cancer (AIRC); Italian League Against Cancer and Italian Ministry of Research; Ministry of Science, Research and Arts Baden-Wrttemberg; Japan; Ministry of Education, Science, Sports, Culture and Technology of Japan [17015052]; Ministry of Health, Labor and Welfare of Japan [H20-002]; NIH US [P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667, R01CA061188, R01CA030022, R01CA048896, R01DE012609, P01CA068384, K07CA104231, R01DE013158]; UCLA Jonsson Comprehensive Cancer Center; National Institute of Environmental Health Sciences [P30ES010126]; AIRC (Italian Agency for Research on Cancer); Swiss League against Cancer; Swiss Research against Cancer/Oncosuisse [KFS-700, OCS-1633] FX This work was supported by INHANCE Pooled Data Project: NCI R03CA113157; Avian and Italy Multicentre studies: Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research; Germany-Saarland study: Ministry of Science, Research and Arts Baden-Wrttemberg; Japan: Scientific Research grant from the Ministry of Education, Science, Sports, Culture and Technology of Japan (17015052) and grant for the Third-Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan (H20-002); Los Angeles study: NIH US [P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667] and the Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center; Milan study: Italian Association for Research on Cancer (AIRC); North Carolina study: NIH US [R01CA061188], and in part by a grant from the National Institute of Environmental Health Sciences [P30ES010126]; Rome study: AIRC (Italian Agency for Research on Cancer); Swiss study: Swiss League against Cancer and the Swiss Research against Cancer/Oncosuisse [KFS-700, OCS-1633]; Seattle-LEO study: (NIH) US [R01CA030022]; Seattle-OralGen study: NIH US [R01CA048896, R01DE012609]; Tampa study: NIH US [P01CA068384, K07CA104231, R01DE013158]. NR 60 TC 20 Z9 20 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2012 VL 21 IS 2 BP 294 EP 304 DI 10.1158/1055-9965.EPI-11-0590 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 889KT UT WOS:000300073300008 PM 22144496 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 Brown, DA Hance, KW Rogers, CJ Sansbury, LB Albert, PS Murphy, G Laiyemo, AO Wang, ZQ Cross, AJ Schatzkin, A Danta, M Srasuebkul, P Amin, J Law, M Breit, SN Lanza, E AF Brown, David A. Hance, Kenneth W. Rogers, Connie J. Sansbury, Leah B. Albert, Paul S. Murphy, Gwen Laiyemo, Adeyinka O. Wang, Zhuoqiao Cross, Amanda J. Schatzkin, Arthur Danta, Mark Srasuebkul, Preeyaporn Amin, Janaki Law, Matthew Breit, Samuel N. Lanza, Elaine TI Serum Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15): A Potential Screening Tool for the Prevention of Colon Cancer? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TGF-BETA SUPERFAMILY; ACTIVATED GENE NAG-1; GROWTH-FACTOR-BETA; DIETARY INTERVENTION; COLORECTAL ADENOMAS; BONE METASTASES; WEIGHT-LOSS; HIGH-FIBER; LOW-FAT; EXPRESSION AB Background: Macrophage inhibitory cytokine-1 (MIC-1/GDF15) mediates nonsteroidal anti-inflammatory drug (NSAID) protection from colonic polyps in mice and is linked to the development of colorectal carcinoma in humans. Therefore, changes in serum MIC-1/GDF15 levels could predict the presence of premalignant colonic polyposis and assist in population screening strategies. Methods: Serum MIC-1/GDF15 levels were measured in subjects in the Polyp Prevention Trial, in which NSAID use and colon cancer risk factors were defined. Subjects had an initial adenoma removed, a repeat colonoscopy removing previously unidentified polyps, and serum MIC-1/GDF15 estimation. Three years later recurrent adenomas were identified and serum MIC-1/GDF15 levels reestimated. The relationship between serum MIC-1/GDF15 levels and adenoma presence or recurrence was examined. Results: Serum MIC-1/GDF15 levels differed by adenoma status and were significantly related to colon cancer risk factors. In addition, mean serum MIC-1/GDF15 levels rose with increasing numbers of adenomas present and high-risk adenoma recurrence. NSAID users had higher serum MIC-1/GDF15 concentrations, which were related to protection from adenoma recurrence. Furthermore, adjusted serum MIC-1/GDF15 levels at final follow-up were related to adenoma recurrence (highest quartile MIC-1/GDF15; OR = 14.7, 95% CI: 3.0-73). Conclusions: These data suggest that MIC-1/GDF15 mediates at least some of the protection afforded by NSAIDs against human colonic polyposis. Furthermore, serum MIC-1/GDF15 levels vary with the development of adnenomatous colonic polyps. Impact: Serum MIC-1/GDF15 determination may hold promise as the first serum screening test to assist the detection of premalignant adenomatous colonic polyposis. Cancer Epidemiol Biomarkers Prev; 21(2); 337-46. (C)2011 AACR. C1 [Brown, David A.; Breit, Samuel N.] St Vincents Hosp, St Vincents Ctr Appl Med Res, Sydney, NSW 2010, Australia. [Danta, Mark] St Vincents Hosp, St Vincents Clin Sch, Sydney, NSW 2010, Australia. [Srasuebkul, Preeyaporn; Amin, Janaki; Law, Matthew] Univ New S Wales, Kirby Inst, Sydney, NSW, Australia. [Murphy, Gwen; Cross, Amanda J.; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Albert, Paul S.] NICHHD, Biostat & Bioinformat Branch, NIH, Bethesda, MD 20892 USA. [Laiyemo, Adeyinka O.] Howard Univ, Coll Med, Div Gastroenterol, Washington, DC USA. [Wang, Zhuoqiao] Informat Management Serv Inc, Silver Spring, MD USA. RP Brown, DA (reprint author), St Vincents Hosp, St Vincents Ctr Appl Med Res, Victoria St, Sydney, NSW 2010, Australia. EM D.Brown@amr.org.au FU NIH; National Cancer Institute; Center for Cancer Research; National Health and Medical Research Council of Australia; New South Wales Health Research and Development Infrastructure grant; St Vincent's Clinic Foundation; NHMRC FX This research was supported in part by grants from Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, The National Cancer Institute Cancer Prevention Fellowship Program, The National Health and Medical Research Council of Australia, a New South Wales Health Research and Development Infrastructure grant and St Vincent's Clinic Foundation grant. D.A. Brown is funded by an NHMRC Career Development Fellowship. The funding sources had no direct or indirect involvement in the design and conduct of the study; nor the collection, management, analysis, and interpretation of the data, nor in the preparation, review, or approval of the manuscript. NR 43 TC 25 Z9 28 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2012 VL 21 IS 2 BP 337 EP 346 DI 10.1158/1055-9965.EPI-11-0786 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 889KT UT WOS:000300073300012 PM 22144502 ER PT J AU McGlynn, KA London, WT AF McGlynn, Katherine A. London, W. Thomas TI International Liver Cancer Incidence Trends-Letter SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter ID HEPATOCELLULAR-CARCINOMA; HEPATITIS-B; C-VIRUS; MONGOLIA C1 [McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [London, W. Thomas] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP McGlynn, KA (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 10 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2012 VL 21 IS 2 BP 384 EP 385 DI 10.1158/1055-9965.EPI-11-1102 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 889KT UT WOS:000300073300018 PM 22169186 ER PT J AU Lu, Y Liu, PY Van den Bergh, F Zellmer, V James, M Wen, WD Grubbs, CJ Lubet, RA You, M AF Lu, Yan Liu, Pengyuan Van den Bergh, Francoise Zellmer, Victoria James, Michael Wen, Weidong Grubbs, Clinton J. Lubet, Ronald A. You, Ming TI Modulation of Gene Expression and Cell-Cycle Signaling Pathways by the EGFR Inhibitor Gefitinib (Iressa) in Rat Urinary Bladder Cancer SO CANCER PREVENTION RESEARCH LA English DT Article ID LET-7 MICRORNAS; TESTIS ANTIGEN; UP-REGULATION; CARCINOMA; MICE; CARCINOGENESIS; PROGRESSION; NETWORKS; TUMORS; N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE AB The epidermal growth factor receptor inhibitor Iressa has shown strong preventive efficacy in the N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) model of bladder cancer in the rat. To explore its antitumor mechanism, we implemented a systems biology approach to characterize gene expression and signaling pathways in rat urinary bladder cancers treated with Iressa. Eleven bladder tumors from control rats, seven tumors from rats treated with Iressa, and seven normal bladder epithelia were profiled by the Affymetrix Rat Exon 1.0 ST Arrays. We identified 713 downregulated and 641 upregulated genes in comparing bladder tumors versus normal bladder epithelia. In addition, 178 genes were downregulated and 96 genes were upregulated when comparing control tumors versus Iressa-treated tumors. Two coexpression modules that were significantly correlated with tumor status and treatment status were identified [r = 0.70, P = 2.80 x 10(-15) (bladder tumor vs. normal bladder epithelium) and r = 0.63, P = 2.00 x 10(-42) (Iressa-treated tumor vs. control tumor), respectively]. Both tumor module and treatment module were enriched for genes involved in cell-cycle processes. Twenty-four and twenty-one highly connected hub genes likely to be key drivers in cell cycle were identified in the tumor module and treatment module, respectively. Analysis of microRNA genes on the array chips showed that tumor module and treatment module were significantly associated with expression levels of let-7c (r = 0.54, P = 3.70 x 10(-8) and r = 0.73, P = 1.50 x 10(-65), respectively). These results suggest that let-7c downregulation and its regulated cell-cycle pathway may play an integral role in governing bladder tumor suppression or collaborative oncogenesis and that Iressa exhibits its preventive efficacy on bladder tumorigenesis by upregulating let-7 and inhibiting the cell cycle. Cell culture study confirmed that the increased expression of let-7c decreases Iressa-treated bladder tumor cell growth. The identified hub genes may also serve as pharmacodynamic or efficacy biomarkers in clinical trials of chemoprevention in human bladder cancer. Cancer Prev Res; 5(2); 248-59. (C) 2011 AACR. C1 [Van den Bergh, Francoise; Zellmer, Victoria; James, Michael; You, Ming] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Ctr Canc, Milwaukee, WI 53226 USA. [Lu, Yan; Liu, Pengyuan] Med Coll Wisconsin, Dept Physiol, Ctr Canc, Milwaukee, WI 53226 USA. [Lu, Yan; Liu, Pengyuan; Wen, Weidong; You, Ming] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Lu, Yan; Liu, Pengyuan; Wen, Weidong; You, Ming] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Grubbs, Clinton J.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Lubet, Ronald A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP You, M (reprint author), Med Coll Wisconsin, Dept Pharmacol & Toxicol, Ctr Canc, Milwaukee, WI 53226 USA. EM myou@mcw.edu FU NCI [HHSN-261200433008C (N01-CN43308)] FX The funding for the studies was provided in part by NCI Contract Number HHSN-261200433008C (N01-CN43308). NR 59 TC 8 Z9 10 U1 2 U2 6 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 248 EP 259 DI 10.1158/1940-6207.CAPR-10-0363 PG 12 WC Oncology SC Oncology GA 888ZO UT WOS:000300043500011 PM 21982874 ER PT J AU Nguyen, MM Ahmann, FR Nagle, RB Hsu, CH Tangrea, JA Pames, HL Sokoloff, MH Gretzer, MB Chow, HHS AF Nguyen, Mike M. Ahmann, Frederick R. Nagle, Raymond B. Hsu, Chiu-Hsieh Tangrea, Joseph A. Pames, Howard L. Sokoloff, Mitchell H. Gretzer, Matthew B. Chow, H-H. Sherry TI Randomized, Double-Blind, Placebo-Controlled Trial of Polyphenon E in Prostate Cancer Patients before Prostatectomy: Evaluation of Potential Chemopreventive Activities SO CANCER PREVENTION RESEARCH LA English DT Article ID GREEN TEA POLYPHENOLS; EPIGALLOCATECHIN GALLATE; GROWTH-FACTOR; TRAMP MICE; CATECHINS; FINASTERIDE; PREVENTION; MODEL; STAGE AB Compelling preclinical and pilot clinical data support the role of green tea polyphenols in prostate cancer prevention. We conducted a randomized, double-blind, placebo-controlled trial of polyphenon E (enriched green tea polyphenol extract) in men with prostate cancer scheduled to undergo radical prostatectomy. The study aimed to determine the bioavailability of green tea polyphenols in prostate tissue and to measure its effects on systemic and tissue biomarkers of prostate cancer carcinogenesis. Participants received either polyphenon E (containing 800 mg epigallocatechin gallate) or placebo daily for 3 to 6 weeks before surgery. Following the intervention, green tea polyphenol levels in the prostatectomy tissue were low to undetectable. Polyphenon E intervention resulted in favorable but not statistically significant changes in serum prostate-specific antigen, serum insulin-like growth factor axis, and oxidative DNA damage in blood leukocytes. Tissue biomarkers of cell proliferation, apoptosis, and angiogenesis in the prostatectomy tissue did not differ between the treatment arms. The proportion of subjects who had a decrease in Gleason score between biopsy and surgical specimens was greater in those on polyphenon E but was not statistically significant. The study's findings of low bioavailability and/or bioaccumulation of green tea polyphenols in prostate tissue and statistically insignificant changes in systemic and tissue biomarkers from 3 to 6 weeks of administration suggests that prostate cancer preventive activity of green tea polyphenols, if occurring, may be through indirect means and/or that the activity may need to be evaluated with longer intervention durations, repeated dosing, or in patients at earlier stages of the disease. Cancer Prev Res; 5(2); 290-8. (C) 2011 AACR. C1 [Nguyen, Mike M.] Univ Arizona, Coll Med, Div Urol, Tucson, AZ 85724 USA. [Ahmann, Frederick R.; Nagle, Raymond B.; Hsu, Chiu-Hsieh; Chow, H-H. Sherry] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. [Tangrea, Joseph A.; Pames, Howard L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Nguyen, MM (reprint author), Univ Arizona, Coll Med, Div Urol, 1501 N Campbell Ave,POB 245077, Tucson, AZ 85724 USA. EM mnguyen@surgery.arizona.edu FU National Cancer Institute [N01CN35158]; Arizona Cancer Center [CA023074] FX This work was supported by a contract (N01CN35158) from the National Cancer Institute and the Arizona Cancer Center Support Grant (CA023074). Clinical Trial Registration: clinicaltrials.gov identifier: NCT00459407. NR 18 TC 40 Z9 41 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD FEB PY 2012 VL 5 IS 2 BP 290 EP 298 DI 10.1158/1940-6207.CAPR-11-0306 PG 9 WC Oncology SC Oncology GA 888ZO UT WOS:000300043500016 PM 22044694 ER PT J AU Nishioka, N Matsuoka, T Yashiro, M Hirakawa, K Olden, K Roberts, JD AF Nishioka, Nobuaki Matsuoka, Tasuku Yashiro, Masakazu Hirakawa, Kosei Olden, Kenneth Roberts, John D. TI Plasminogen activator inhibitor 1 RNAi suppresses gastric cancer metastasis in vivo SO CANCER SCIENCE LA English DT Article ID PHASE-II TRIAL; TUMOR-GROWTH; CARCINOMA-CELLS; NUDE-MICE; ANGIOGENESIS; INVASION; MELANOMA; THERAPY; GENE; 5-FLUOROURACIL AB Cancer metastasis remains the primary cause of pain, suffering, and death in cancer patients, and even the most current therapeutic strategies have not been highly successful in preventing or inhibiting metastasis. In most patients with scirrhous gastric cancer (one of the most aggressive of diffuse-type gastric cancer), recurrence occurs even after potentially curative resection, most frequently in the form of peritoneal metastasis. Given that the occurrence of diffuse-type gastric cancers has been increasing, the development of new strategies to combat metastasis of this disease is critically important. Plasminogen activator inhibitor-1 (PAI-1) is a critical factor in cancer progression; thus, PAI-1 RNAi may be an effective therapy against cancer metastasis. In the present study, we used an RNAi technique to reduce PAI-1 expression in an in vivo model system for gastric cancer metastasis. Ex vivo plasmid transfection and adenovirus infection were tested as mechanisms to incorporate specific PAI-1 RNAi vectors into human gastric carcinoma cells. Both approaches significantly decreased peritoneal tumor growth and the formation of bloody ascites in the mouse model, suggesting that this approach may provide a new, effective strategy for inhibiting cancer metastasis. (Cancer Sci 2012; 103: 228232) C1 [Nishioka, Nobuaki; Matsuoka, Tasuku; Olden, Kenneth; Roberts, John D.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Yashiro, Masakazu; Hirakawa, Kosei] Osaka City Univ, Grad Sch Med, Dept Surg Oncol, Osaka 558, Japan. RP Matsuoka, T (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. EM matsuoka@med.osaka-cu.ac.jp FU National Institute of Health (NIH); National Institute of Environmental Health Sciences (NIEHS) FX This work was supported by the Intramural Research Program of the National Institute of Health (NIH) and National Institute of Environmental Health Sciences (NIEHS). The authors thank Dr Steven K. Akiyama (Laboratory of Molecular Carcinogenesis, NIEHS, Piedmont, NC, USA) for helpful discussions. NR 31 TC 13 Z9 14 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD FEB PY 2012 VL 103 IS 2 BP 228 EP 232 DI 10.1111/j.1349-7006.2011.02155.x PG 5 WC Oncology SC Oncology GA 884UJ UT WOS:000299734000012 PM 22098548 ER PT J AU Barry, KH Koutros, S Andreotti, G Sandler, DP Burdette, LA Yeager, M Freeman, LEB Lubin, JH Ma, XM Zheng, TZ Alavanja, MCR Berndt, SI AF Barry, Kathryn Hughes Koutros, Stella Andreotti, Gabriella Sandler, Dale P. Burdette, Laurie A. Yeager, Meredith Freeman, Laura E. Beane Lubin, Jay H. Ma, Xiaomei Zheng, Tongzhang Alavanja, Michael C. R. Berndt, Sonja I. TI Genetic variation in nucleotide excision repair pathway genes, pesticide exposure and prostate cancer risk SO CARCINOGENESIS LA English DT Article ID AGRICULTURAL HEALTH; DNA-DAMAGE; CHROMOSOMAL-ABERRATIONS; WORKERS; ASSOCIATION; CELLS; POLYMORPHISMS; LYMPHOCYTES; APPLICATORS; CARBOFURAN AB Previous research demonstrates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, human biomonitoring studies indicate increased genetic damage (e.g. chromosomal aberrations) with pesticide exposure. Given that the nucleotide excision repair (NER) pathway repairs a broad range of DNA damage, we evaluated interactions between pesticide exposure and 324 single-nucleotide polymorphisms (SNPs) tagging 27 NER genes among 776 prostate cancer cases and 1444 male controls in a nested case-control study of white Agricultural Health Study pesticide applicators. We determined interaction P values using likelihood ratio tests from logistic regression models and three-level pesticide variables (none/low/high) based on lifetime days of use weighted to an intensity score. We adjusted for multiple comparisons using the false discovery rate (FDR) method. Of the 17 interactions that met FDR < 0.2, 3 displayed a monotonic increase in prostate cancer risk with increasing exposure in one genotype group and no significant association in the other group. Men carrying the variant A allele at ERCC1 rs2298881 exhibited increased prostate cancer risk with high versus no fonofos use [odds ratio (OR) 2.98; 95% confidence interval (CI) 1.65-5.39; P-interact = 3.6 x 10(-4); FDR-adjusted P = 0.11]. Men carrying the homozygous wild-type TT genotype at two correlated CDK7 SNPs, rs11744596 and rs2932778 (r(2) = 1.0), exhibited increased risk with high versus no carbofuran use (OR 2.01; 95% CI 1.31-3.10 for rs11744596; P-interact = 7.2 x 10(-4); FDR-adjusted P = 0.09). In contrast, we did not observe associations among men with other genotypes at these loci. While requiring replication, our findings suggest a role for NER genetic variation in pesticide-associated prostate cancer risk. C1 [Barry, Kathryn Hughes] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Barry, Kathryn Hughes; Ma, Xiaomei] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT 06520 USA. [Sandler, Dale P.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Burdette, Laurie A.; Yeager, Meredith] NCI, Core Genotyping Facil, Frederick, MD 21702 USA. [Zheng, Tongzhang] Yale Univ, Div Environm Hlth Sci, Sch Publ Hlth, New Haven, CT 06520 USA. RP Barry, KH (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 8111,MSC 7240, Bethesda, MD 20892 USA. EM barrykh@mail.nih.gov RI Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Sandler, Dale/0000-0002-6776-0018 FU National Institutes of Health (National Cancer Institute, Division of Cancer Epidemiology and Genetics) [Z01CP010119]; National Institutes of Health (National Institute of Environmental Health Sciences) [Z01ES049030]; National Institutes of Health (National Cancer Institute) [T32 CA105666] FX National Institutes of Health (Intramural Research Program of the National Cancer Institute, Division of Cancer Epidemiology and Genetics, Z01CP010119; Intramural Research Program of the National Institute of Environmental Health Sciences, Z01ES049030 and National Cancer Institute grant T32 CA105666 to K.H.B.). NR 49 TC 18 Z9 19 U1 1 U2 19 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 331 EP 337 DI 10.1093/carcin/bgr258 PG 7 WC Oncology SC Oncology GA 888YF UT WOS:000300039800013 PM 22102698 ER PT J AU Wang, ML Liu, F Hsing, AW Wang, X Shao, Q Qi, J Ye, Y Wang, Z Chen, HY Gao, X Wang, GZ Chu, LW Ding, Q OuYang, J Gao, X Huang, YC Chen, YB Gao, YT Zhang, ZF Rao, JY Shi, R Wu, QJ Zhang, YY Jiang, HW Zheng, J Hu, YL Guo, L Lin, XL Tao, S Jin, GF Sun, JL Lu, DR Zheng, SL Sun, YH Mo, ZN Yin, CJ Zhang, ZD Xu, JF AF Wang, Meilin Liu, Fang Hsing, Ann W. Wang, Xiang Shao, Qiang Qi, Jun Ye, Yu Wang, Zhong Chen, Hongyan Gao, Xin Wang, Guozeng Chu, Lisa W. Ding, Qiang OuYang, Jun Gao, Xu Huang, Yichen Chen, Yanbo Gao, Yu-Tang Zhang, Zuo-Feng Rao, Jiangyu Shi, Rong Wu, Qijun Zhang, Yuanyuan Jiang, Haowen Zheng, Jie Hu, Yanlin Guo, Ling Lin, Xiaoling Tao, Sha Jin, Guangfu Sun, Jielin Lu, Daru Zheng, S. Lilly Sun, Yinghao Mo, Zengnan Yin, Changjun Zhang, Zhengdong Xu, Jianfeng TI Replication and cumulative effects of GWAS-identified genetic variations for prostate cancer in Asians: a case-control study in the ChinaPCa consortium SO CARCINOGENESIS LA English DT Article ID PROTEIN-COUPLED RECEPTOR; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; RISK; EXPRESSION; VARIANTS; MULTIPLE; CLONING; HUMANS; GPRC6A AB A recent genome-wide association study has identified five new genetic variants for prostate cancer susceptibility in a Japanese population, but it is unknown whether these newly identified variants are associated with prostate cancer risk in other populations, including Chinese men. We genotyped these five variants in a case-control study of 1524 patients diagnosed with prostate cancer and 2169 control subjects from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). We found that three of the five genetic variants were associated with prostate cancer risk (P = 4.33 x 10(-8) for rs12653946 at 5p15, 4.43 x 10(-5) for rs339331 at 6q22 and 8.42 x 10(-4) for rs9600079 at 13q22, respectively). A cumulative effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (P-trend = 2.58 x 10(-13)), and men with 5-6 risk alleles had a 2-fold higher risk of prostate cancer than men with 0-2 risk alleles (odds ratio = 2.26, 95% confidence interval = 1.78-2.87). Furthermore, rs339331 T allele was significantly associated with RFX6 and GPRC6A higher messenger RNA expression, compared with the C allele. However, none of the variants was associated with clinical stage, Gleason score or family history. These results provide further evidence that the risk loci identified in Japanese men also contribute to prostate cancer susceptibility in Chinese men. C1 [Wang, Meilin; Zhang, Zhengdong] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China. [Wang, Meilin; Zhang, Zhengdong] Nanjing Med Univ, Dept Mol & Genet Toxicol, Key Lab Modern Toxicol, Minist Educ,Sch Publ Hlth, Nanjing 210029, Jiangsu, Peoples R China. [Wang, Meilin; Zhang, Zhengdong] Nanjing Med Univ, Dept Occupat Med & Environm Hlth, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Ctr Canc, Nanjing 210029, Jiangsu, Peoples R China. [Liu, Fang; Chen, Hongyan; Lin, Xiaoling; Sun, Jielin; Lu, Daru; Zheng, S. Lilly; Xu, Jianfeng] Fudan Univ, Sch Life Sci, Fudan VARI Ctr Genet Epidemiol, Shanghai 200433, Peoples R China. [Hsing, Ann W.; Chu, Lisa W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20894 USA. [Wang, Xiang; Ding, Qiang; Jiang, Haowen; Zheng, Jie; Xu, Jianfeng] Fudan Univ, Huashan Hosp, Dept Urol, Shanghai 200032, Peoples R China. [Shao, Qiang] Suzhou Municipal Hosp, Dept Urol, Suzhou 215000, Peoples R China. [Qi, Jun; Huang, Yichen; Hu, Yanlin] Shanghai Jiao Tong Univ, Dept Urol, Xinhua Hosp, Sch Med, Shanghai 200025, Peoples R China. [Ye, Yu; Mo, Zengnan] Guangxi Med Univ, Affiliated Hosp 1, Dept Urol, Guangxi 530021, Peoples R China. [Wang, Zhong; Chen, Yanbo] Shanghai Jiao Tong Univ, Dept Urol, Sch Med, Peoples Hosp 9, Shanghai 200025, Peoples R China. [Chen, Hongyan; Lu, Daru; Xu, Jianfeng] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China. [Gao, Xin] Sun Yat Sen Univ, Dept Urol, Affiliated Hosp 3, Guangzhou 510630, Guangdong, Peoples R China. [Wang, Guozeng] Pudong Gongli Hosp, Dept Urol, Shanghai 200135, Peoples R China. [OuYang, Jun] Suzhou Univ, Peoples Hosp 1, Dept Urol, Suzhou 215000, Peoples R China. [Gao, Xu; Sun, Yinghao] Second Mil Med Univ, Dept Urol, Changhai Hosp, Shanghai 200433, Peoples R China. [Gao, Yu-Tang] Shanghai Canc Inst, Shanghai 200032, Peoples R China. [Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90001 USA. [Rao, Jiangyu] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90001 USA. [Shi, Rong; Wu, Qijun] Shanghai Jiao Tong Univ, Sch Publ Hlth, Shanghai 200025, Peoples R China. [Zhang, Yuanyuan] Wake Forest Univ, Bowman Gray Sch Med, Dept Urol, Winston Salem, NC 27106 USA. [Guo, Ling; Tao, Sha; Xu, Jianfeng] Van Andel Res Inst, Grand Rapids, MI 49503 USA. [Jin, Guangfu; Sun, Jielin; Zheng, S. Lilly; Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC 27106 USA. [Yin, Changjun] Nanjing Med Univ, Dept Urol, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China. RP Zhang, ZD (reprint author), Nanjing Med Univ, State Key Lab Reprod Med, 140 Hanzhong Rd, Nanjing 210029, Jiangsu, Peoples R China. EM drzdzhang@gmail.com; drzdzhang@gmail.com; jxu@wfubmc.edu RI tao, sha/B-7750-2012 FU National Cancer Institute [1R01CA129684-01]; National Natural Science Foundation of China [30872084, 30972444, 81102089]; Natural Science Foundation of Jiangsu Province [BK2010080, BK2011773]; Jiangsu Higher Education Institutions (Public Health and Preventive Medicine) FX This study was partly supported by National Cancer Institute (1R01CA129684-01), National Natural Science Foundation of China (30872084, 30972444, 81102089), the Key Program of Natural Science Foundation of Jiangsu Province (BK2010080), Natural Science Foundation of Jiangsu Province (BK2011773) and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine). NR 27 TC 28 Z9 28 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 2012 VL 33 IS 2 BP 356 EP 360 DI 10.1093/carcin/bgr279 PG 5 WC Oncology SC Oncology GA 888YF UT WOS:000300039800016 PM 22114074 ER PT J AU Chahal, H McClelland, RL Tandri, H Jain, A Turkbey, EB Hundley, WG Barr, RG Kizer, J Lima, JAC Bluemke, DA Kawut, SM AF Chahal, Harjit McClelland, Robyn L. Tandri, Harikrishna Jain, Aditya Turkbey, Evrim B. Hundley, W. Gregory Barr, R. Graham Kizer, Jorge Lima, Joao A. C. Bluemke, David A. Kawut, Steven M. TI Obesity and Right Ventricular Structure and Function The MESA-Right Ventricle Study SO CHEST LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; CARDIOVASCULAR MAGNETIC-RESONANCE; WEIGHT-LOSS; ARTERIAL-HYPERTENSION; HEART-FAILURE; MYOCARDIAL PERFORMANCE; ATHEROSCLEROSIS MESA; CARDIAC STRUCTURE; CARDIOMYOPATHY; ASSOCIATION AB Background: The relationship between obesity and right ventricular (RV) morphology is not well studied. We aimed to determine the association between obesity and RV structure and function in a large multiethnic population-based cohort. Methods: The MESA-Right Ventricle Study measured RV mass and volumes by cardiac MRI in participants aged 45 to 84 years without clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were divided into three categories based on BMI: lean (<= 24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese (>= 30 kg/m(2)). Results: The study sample included 4,127 participants. After adjustment for demographics, height, education, and cardiovascular risk factors, overweight and obese participants had greater RV mass (6% and 9% greater, respectively), larger RV end-diastolic volume (8% and 18% greater, respectively), larger RV stroke volume (7% and 16% greater, respectively), and lower RV ejection fraction ( >= 1% lower) than lean participants (all P < .001). These findings persisted after adjusting for the respective left ventricular (LV) parameters. Conclusions: Overweight and obesity were independently associated with differences in RV morphology even after adjustment for the respective LV measure. This association could be explained by increased RV afterload, increased blood volume, hormonal effects, or direct obesity-related myocardial effects. CHEST 2012; 141(2):388-395 C1 [Kawut, Steven M.] Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Dept Med, Philadelphia, PA 19104 USA. [Chahal, Harjit; Jain, Aditya] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Tandri, Harikrishna; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [McClelland, Robyn L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Turkbey, Evrim B.; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Dept Radiol & Imaging Sci, NIH, Ctr Clin, Bethesda, MD USA. [Hundley, W. Gregory] Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27109 USA. [Barr, R. Graham] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Kizer, Jorge] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Kawut, Steven M.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Kawut, SM (reprint author), Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Dept Med, 718 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kawut@upenn.edu OI Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health [R01-HL086719, R01-HL077612, N01-HC95159, N01-HC95169]; US Environmental Protection Agency; Alphal Foundation; Columbia University FX This work was supported by National Institutes of Health [Grants R01-HL086719, R01-HL077612, and N01-HC95159 through N01-HC95169].; The authors have reported to CHEST the following conflicts of interest: Dr Barr currently receives grant funding for research support from the National Institutes of Health, US Environmental Protection Agency, Alphal Foundation, and Columbia University. Cenesta Health donated a nutritional supplement for NIT-sponsored trial. Drs Chahal, McClelland, Tandri, Jain, Turkbey, Hundley, Barr, Kizer, Lima, Bluemke, and Kawut, have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may he discussed in this article. NR 40 TC 40 Z9 41 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 388 EP 395 DI 10.1378/chest.11-0172 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 887HQ UT WOS:000299917900016 PM 21868467 ER PT J AU Eberlein, M Permutt, S Chahla, MF Bolukbas, S Nathan, SD Shlobin, OA Shelhamer, JH Reed, RM Pearse, DB Orens, JB Brower, RG AF Eberlein, Michael Permutt, Solbert Chahla, Mayy F. Bolukbas, Servet Nathan, Steven D. Shlobin, Oksana A. Shelhamer, James H. Reed, Robert M. Pearse, David B. Orens, Jonathan B. Brower, Roy G. TI Lung Size Mismatch in Bilateral Lung Transplantation is Associated With Allograft Function and Bronchiolitis Obliterans Syndrome SO CHEST LA English DT Article ID MAXIMAL EXPIRATORY FLOW; PULMONARY SURFACTANT ACTIVITY; HEART-LUNG; RESIDUAL VOLUME; RECOIL PRESSURE; VITAL CAPACITY; CANINE LUNG; DONOR; RESTRICTION; MECHANICS AB Background: Size mismatch between donor lungs and a recipient thorax could affect the major determinants of maximal expiratory airflow: airway resistance, propensity of airways to collapse, and lung elastic recoil. Methods: A retrospective review of 159 adults who received bilateral lung transplants was performed. The predicted total lung capacity (pTLC) for donors and recipients was calculated based on sex and height. Size matching was represented using the following formula: pTLC ratio = donor pTLC/recipient pTLC. Patients were grouped according to those with a pTLC ratio > 1.0 (oversized) or those with a pTLC ratio 1.0 (undersized). Allograft function was analyzed in relation to the pTLC ratio and to recipient and donor predicted function. Results: The 96 patients in the oversized cohort had a mean pTLC ratio of 1.16 +/- 0.13 vs 0.89 +/- 0.09 in the 63 patients of the undersized group. At 1 to 6 months posttransplant, the patients in the oversized cohort had higher FEV1/FVC ratios (0.895 +/- 0.13 vs 0.821 +/- 0.13, P < .01) and lower time constant estimates of lung emptying (0.38 +/- 0.2 vs 0.64 +/- 0.4, P < .01) than patients in the undersized cohort. Although the FVCs expressed as % predicted for the recipient were not different between cohorts, the FVCs expressed as % predicted for the donor organ were lower in the oversized cohort compared with the undersized cohort (at 1-6 months, 52.4% +/- 17.1% vs 65.3% 18.3%, P < .001). Kaplan-Meier estimates for the occurrence of bronchiolitis obliterans syndrome (BOS) showed that patients in the oversized cohort had a lower probability of BOS (P < .001). Conclusions: A pTLC ratio > 1.0, suggestive of an oversized allograft, is associated with higher expiratory airflow capacity and a less frequent occurrence of BOS. CHEST 2012; 141(2):451-460 C1 [Eberlein, Michael; Permutt, Solbert; Pearse, David B.; Orens, Jonathan B.; Brower, Roy G.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA. [Chahla, Mayy F.] Johns Hopkins Univ, Sch Med, Div Hosp Med, Baltimore, MD USA. [Reed, Robert M.] Univ Maryland, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA. [Eberlein, Michael; Shelhamer, James H.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Bolukbas, Servet] Horst Schmidt Klin, Dept Thorac Surg, Wiesbaden, Germany. [Nathan, Steven D.; Shlobin, Oksana A.] Inova Fairfax Hosp, Adv Lung Dis Program, Falls Church, VA USA. RP Eberlein, M (reprint author), Univ Iowa, Div Pulm Crit Care & Occupat Med, Carver Coll Med, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM michael-eberlein@uiowa.edu NR 37 TC 33 Z9 33 U1 1 U2 2 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 451 EP 460 DI 10.1378/chest.11-0767 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 887HQ UT WOS:000299917900024 PM 21799025 ER PT J AU Lauer, MS AF Lauer, Michael S. TI Advancing Cardiovascular Research SO CHEST LA English DT Article ID CORONARY-ARTERY-DISEASE; TYPE-2 DIABETES-MELLITUS; MYOCARDIAL-INFARCTION; UNITED-STATES; HEART-DISEASE; CLINICAL-PRACTICE; OUTCOMES; RISK; THERAPY; 9P21 AB Over the past 50 years, we have seen dramatic changes in cardiovascular science and clinical care, accompanied by marked declines in the morbidity and mortality. Nonetheless, cardiovascular disease remains the leading cause of death and disability in the world, and its nature is changing as Americans become older, fatter, and ethnically more diverse. Instead of young or middle-aged men with ST-segment elevation myocardial infarction, the "typical" cardiac patient now presents with acute coronary syndrome or with complications related to chronic hypertension or ischemic heart disease, including heart failure, sudden death, and atrial fibrillation. Analogously, structural heart disease is now dominated by degenerative valve or congenital disease, far more common than rheumatic disease. The changing clinical scene presents cardiovascular scientists with a number of opportunities and challenges, including taking advantage of high-throughput technologies to elucidate complex disease mechanisms, accelerating development and implementation of evidence-based strategies, assessing evolving technologies of unclear value, addressing a global epidemic of cardiovascular disease, and maintaining high levels of innovation in a time of budgetary constraint and economic turmoil. CHEST 2012; 141(2):500-505 C1 NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr,Rm 8128, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 58 TC 9 Z9 9 U1 0 U2 2 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 500 EP 505 DI 10.1378/chest.11-2521 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 887HQ UT WOS:000299917900030 PM 22315116 ER PT J AU Bellanti, JA Lin, FYC Chu, C Shiloach, J Leppla, SH Benavides, GA Karpas, A Moayeri, M Guo, C Robbins, JB Schneerson, R AF Bellanti, Joseph A. Lin, Feng-Ying C. Chu, Chiayung Shiloach, Joseph Leppla, Stephen H. Benavides, German A. Karpas, Arthur Moayeri, Mahtab Guo, Chunyan Robbins, John B. Schneerson, Rachel TI Phase 1 Study of a Recombinant Mutant Protective Antigen of Bacillus anthracis SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID VACCINE ADSORBED AVA; INHALATION ANTHRAX; ANTIBODY-RESPONSE; LETHAL FACTOR; EDEMA FACTOR; TOXIN GENES; IMMUNOGENICITY; CEREUS; INFECTION; CORRELATE AB A phase 1 study of a recombinant mutant protective antigen (rPA) vaccine was conducted in 186 healthy adults aged 18 to 45 years. Volunteers were randomized to receive one of three formulations of rPA (formalin treated, alum adsorbed, or both), in 10- or 20-mu g dosages each, or the licensed vaccine, AVA. Three injections were given at 2-month intervals and a 4th 1 year after the 3rd. Vaccinees were examined at the clinic once following each injection, at 48 to 72 h postinjection. Adverse reactions were recorded in diaries for 7 days. Sera were collected before each injection and 1 week after the 1st, 2 weeks after the 3rd and 4th, and 1 year after the 4th. Serum anti-PA IgG was assayed by enzyme-linked immunosorbent assay (ELISA) and toxin neutralization assay (TNA). All formulations at both dosages were safe and immunogenic, inducing booster responses, with the highest antibody levels following the 4th injection (354 to 732 mu g/ml). The lowest levels were induced by the formalin-only-treated rPA; there was no statistical difference between levels induced by alum-adsorbed and formalin-treated/alum-adsorbed rPA or by the two dosages. The antibody levels declined in all groups during the 1-year intervals after the 3rd and 4th injections but less so during the 2nd year, after the 4th injection (fold decreases were 10 to 25 versus 3.4 to 7.0, P < 0.001). There were too few AVA recipients for statistical comparisons, but their antibody levels followed those of rPA. Anti-rPA measured by ELISA correlated with TNA titers (r = 0.97). These data support studying alum-adsorbed rPA in children. C1 [Lin, Feng-Ying C.; Chu, Chiayung; Karpas, Arthur; Guo, Chunyan; Robbins, John B.; Schneerson, Rachel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev & Mol Immun, NIH, Bethesda, MD USA. [Bellanti, Joseph A.; Benavides, German A.] Georgetown Univ, Med Ctr, Int Ctr Interdisciplinary Studies Immunol, Washington, DC 20007 USA. [Bellanti, Joseph A.; Benavides, German A.] Georgetown Univ, Sch Med, Washington, DC USA. [Shiloach, Joseph] NIDDK, Biotechnol Unit, Lab Cellular & Dev Biol, NIH, Bethesda, MD USA. [Leppla, Stephen H.; Moayeri, Mahtab] NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA. RP Schneerson, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev & Mol Immun, NIH, Bethesda, MD USA. EM schneerr@mail.nih.gov OI Bellanti, Joseph/0000-0002-5038-7202 FU Division of Intramural Research, NICHD, National Institutes of Health; Division of Intramural Research, NIAID, National Institutes of Health FX This research was supported by the Divisions of Intramural Research, NICHD and NIAID, National Institutes of Health. NR 28 TC 7 Z9 7 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD FEB PY 2012 VL 19 IS 2 BP 140 EP 145 DI 10.1128/CVI.05556-11 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 889AB UT WOS:000300044800004 PM 22190398 ER PT J AU Smith, WM Lange, JM Sturm, AC Tanner, SM Mauger, TF AF Smith, Wendy M. Lange, Julie M. Sturm, Amy C. Tanner, Stephan M. Mauger, Thomas F. TI Familial Peripheral Keratopathy Without PAX6 Mutation SO CORNEA LA English DT Article DE stem cell; aniridia; corectopia; PAX6 ID AUTOSOMAL-DOMINANT KERATITIS; ANIRIDIA; SPECTRUM AB Purpose: To describe the clinical features of a familial abnormality of the corneal stem cells and to investigate the role of PAX6 mutations in the affected family members. Methods: A family with multiple generations of peripheral keratopathy was evaluated. Because of the corneal phenotypic similarity to aniridia-related keratopathy, it was hypothesized that the affected patients might have a dominantly inherited mutation of PAX6 on chromosome 11. Commercial sequencing of germline DNA from 1 affected family member did not identify any PAX6 mutations in the exons or intron-exon boundary regions. Because the commercial analysis is not designed to identify PAX6 deletions, germline DNA was collected from 5 unaffected and 2 additional affected family members. DNA repeat markers in the region of PAX6 were analyzed to determine whether this chromosomal region segregates with the disease phenotype. Results: Affected family members with this autosomal dominant peripheral corneal abnormality showed evidence of progressive corneal stem cell dysfunction. Several individuals demonstrated corectopia, and 1 individual had ectropion uvea but no other iris or ocular abnormalities associated with aniridia. Genotyping data of affected and unaffected family members demonstrated that the PAX6 region does not segregate with the disease phenotype. Conclusions: The features of this autosomal dominant abnormality show some similarity to aniridia, although the classic characteristics of severe iris hypoplasia and macular hypoplasia are absent. Mutational screening and genotyping could not conclusively clarify a role for PAX6 in this disease phenotype, suggesting that it is a distinct clinical and genetic disease entity, not a variant of aniridia. C1 [Smith, Wendy M.; Lange, Julie M.; Mauger, Thomas F.] Ohio State Univ, Dept Ophthalmol, Havener Eye Inst, Columbus, OH 43212 USA. [Smith, Wendy M.] NEI, NIH, Bethesda, MD 20892 USA. [Sturm, Amy C.] Ohio State Univ, Coll Med, Div Human Genet, Columbus, OH 43212 USA. [Tanner, Stephan M.] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43212 USA. RP Mauger, TF (reprint author), Ohio State Univ, Dept Ophthalmol, Havener Eye Inst, 915 Olentangy River Rd, Columbus, OH 43212 USA. EM thomas.mauger@osumc.edu RI Sturm, Amy/E-4162-2011 NR 9 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD FEB PY 2012 VL 31 IS 2 BP 130 EP 133 DI 10.1097/ICO.0b013e3182222779 PG 4 WC Ophthalmology SC Ophthalmology GA 889FQ UT WOS:000300059400006 PM 22146551 ER PT J AU Yau, JWY Xie, J Lamoureux, E Klein, R Klein, BEK Cotch, MF Bertoni, AG Shea, S Wong, TY AF Yau, Joanne Wen Yee Xie, Jing Lamoureux, Ecosse Klein, Ronald Klein, Barbara E. K. Cotch, Mary Frances Bertoni, Alain G. Shea, Steven Wong, Tien Y. TI Retinal microvascular calibre and risk of incident diabetes: The multi-ethnic study of atherosclerosis SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Retinal microvascular calibre; Retinopathy; Diabetes; Impaired fasting glucose ID LIFE-STYLE AUSDIAB; IMPAIRED FASTING GLUCOSE; BLUE MOUNTAINS EYE; VASCULAR CALIBER; VESSEL DIAMETERS; SUBSEQUENT RISK; RETINOPATHY; MELLITUS; OBESITY; ABNORMALITIES AB Aim: To prospectively examine the association of retinal microvascular signs with incident diabetes and impaired fasting glucose (IFG) in a multi-ethnic population-based cohort. Methods: The multi-ethnic study of atherosclerosis comprised Caucasians, African-Americans, Hispanics and Chinese aged 45-84 years. Retinal vascular calibre and retinopathy were quantified from baseline retinal photographs. Incident diabetes and IFG were ascertained prospectively. Results: After a median follow-up of 3 years, 243 (4.9%) people developed diabetes and 565 (15.0%) developed IFG. After adjusting for known risk factors, participants with wider retinal arteriolar calibre had a higher risk of developing diabetes [HR: 1.60; 95% CI: 1.12-2.29, p = 0.011 comparing highest with lowest arteriolar calibre tertile]. In ethnic subgroup analysis, the association between wider retinal arteriolar calibre and incident diabetes was stronger and statistically significant only in Caucasians [HR: 2.78; 95% CI: 1.37-5.62, p = 0.005]. Retinal venular calibre and retinopathy signs were not related to risk of diabetes or IFG. Conclusion: Wider retinal arteriolar calibre is independently associated with an increased risk of diabetes, supporting a possible role for early arteriolar changes in diabetes development. This effect was largely seen in Caucasians, and not in other ethnic groups, and may reflect ethnic differences in susceptibility to diabetes from microvascular pathways. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Yau, Joanne Wen Yee; Xie, Jing; Lamoureux, Ecosse; Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, Melbourne, Vic 3002, Australia. [Lamoureux, Ecosse; Wong, Tien Y.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore. [Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Bertoni, Alain G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Shea, Steven] Columbia Univ, Dept Med, New York, NY USA. [Shea, Steven] Columbia Univ, Dept Epidemiol, New York, NY USA. RP Yau, JWY (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia. EM jwyau@unimelb.edu.au OI Cotch, Mary Frances/0000-0002-2046-4350; Klein, Ronald/0000-0002-4428-6237 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165, N01-HC-95169]; NIH from the National Eye Institute [Z01EY000403]; National Institutes of Health [HL69979-03]; National Health and Medical Research Council (NHMRC), Australia [52993] FX This research was supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute and NIH Intramural Research award Z01EY000403 from the National Eye Institute (MFC). Additional support was provided by National Institutes of Health grants HL69979-03 (Klein R. and Wong T.Y.) and the National Health and Medical Research Council (NHMRC), 52993, Australia (Wong T.Y.). NR 28 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD FEB PY 2012 VL 95 IS 2 BP 265 EP 274 DI 10.1016/j.diabres.2011.10.027 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 887TS UT WOS:000299953900019 PM 22088792 ER PT J AU Morens, DM Taubenberger, JK AF Morens, David M. Taubenberger, Jeffery K. TI 1918 Influenza, a Puzzle with Missing Pieces SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material ID PNEUMONIA; DEATH C1 [Morens, David M.; Taubenberger, Jeffery K.] NIAID, NIH, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, NIH, Bldg 31,Rm 7A03, Bethesda, MD 20892 USA. EM dmorens@niaid.nih.gov NR 8 TC 11 Z9 11 U1 0 U2 7 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD FEB PY 2012 VL 18 IS 2 BP 332 EP 335 DI 10.3201/eid1802.111409 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 889MU UT WOS:000300078600026 PM 22304897 ER PT J AU Matsuura, K Fujimoto, K Fu, LZ Shi, YB AF Matsuura, Kazuo Fujimoto, Kenta Fu, Liezhen Shi, Yun-Bo TI Liganded Thyroid Hormone Receptor Induces Nucleosome Removal and Histone Modifications to Activate Transcription during Larval Intestinal Cell Death and Adult Stem Cell Development SO ENDOCRINOLOGY LA English DT Article ID XENOPUS-LAEVIS METAMORPHOSIS; AMPHIBIAN METAMORPHOSIS; POSTEMBRYONIC DEVELOPMENT; CHROMATIN MODIFICATIONS; VERTEBRATE DEVELOPMENT; FROG METAMORPHOSIS; GENE-EXPRESSION; HUMAN GENOME; COMPLEXES; METHYLATION AB Thyroid hormone (T-3) plays an important role in regulating multiple cellular and metabolic processes, including cell proliferation, cell death, and energy metabolism, in vertebrates. Dysregulation of T-3 signaling results in developmental abnormalities, metabolic defects, and even cancer. We used T-3-dependent Xenopus metamorphosis as a model to study how T-3 regulates transcription during vertebrate development. T-3 exerts its metamorphic effects through T-3 receptors (TR). TR recruits, in a T-3-dependent manner, cofactor complexes that can carry out chromatin remodeling/histone modifications. Whether and how histone modifications change upon gene regulation by TR during vertebrate development is largely unknown. Here we analyzed histone modifications at T-3 target genes during intestinal metamorphosis, a process that involves essentially total apoptotic degeneration of the simple larval epithelium and de novo development of the adult epithelial stem cells, followed by their proliferation and differentiation into the complex adult epithelium. We demonstrated for the first time in vivo during vertebrate development that TR induces the removal of core histones at the promoter region and the recruitment of RNA polymerase. Furthermore, a number of histone activation and repression marks have been defined based on correlations with mRNA levels in cell cultures. Most but not all correlate with gene expression induced by liganded TR during development, suggesting that tissue and developmental context influences the roles of histone modifications in gene regulation. Our findings provide important mechanistic insights on how chromatin remodeling affects developmental gene regulation in vivo. (Endocrinology 153: 961-972, 2012) C1 [Matsuura, Kazuo; Fujimoto, Kenta; Fu, Liezhen; Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, Program Cellular Regulat & Metab,NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, Program Cellular Regulat & Metab,NIH, Bldg 18T,Room 106,18 Lib Dr,MSC 5431, Bethesda, MD 20892 USA. EM shi@helix.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 68 TC 16 Z9 16 U1 0 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2012 VL 153 IS 2 BP 961 EP 972 DI 10.1210/en.2011-1736 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 887LF UT WOS:000299928200043 PM 22147009 ER PT J AU Su, D Cha, YM West, AE AF Su, Dan Cha, Young May West, Anne E. TI Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes SO EPIGENETICS LA English DT Article DE MeCP2; immediate-early genes; chromatin regulation; RNA polymerase II; transcriptional initiation and elongation; Junb; Arc; cocaine; striatumform ID CPG-BINDING PROTEIN-2; RNA-POLYMERASE-II; RETT-SYNDROME; MOUSE MODEL; NUCLEUS-ACCUMBENS; DNA METHYLATION; HISTONE DEACETYLASE; CHROMATIN STATE; NEURONAL MECP2; MUTANT MICE AB Loss-of-function mutations in the methyl-DNA binding protein MeCP2 are associated with neurological dysfunction and impaired neural plasticity. However, the transcriptional changes that underlie these deficits remain poorly understood. Here, we show that mice bearing a C-terminal truncating mutation in Mecp2 (Mecp2(308)) are hypersensitive to the locomotor stimulating effects of cocaine. Furthermore, these mice have gene-specific alterations in striatal immediate-early gene (IEG) induction following cocaine administration. MeCP2 mutant mice show normal levels of baseline and cocaine-induced striatal Fos expression compared with their wild-type littermates. However, the mutant mice have enhanced cocaine-induced transcription of Junb and Arc. At the chromatin level, we find increased histone H3 acetylation at gene promoters in the Mecp2 mutant mice compared with their wild-type littermates, whereas two sites of repressive histone methylation are unchanged. Interestingly, we find that MeCP2 mutant mice show increased steady-state association of elongation-competent RNA Polymerase II (RNAP II) with the Junb and Arc promoters, whereas levels of RNAP II association at the Fos promoter are unchanged. These data reveal a gene-specific effect of MeCP2 on the recruitment of RNAP II to gene promoters that may modulate the inducibility of IEGs. In addition, our findings raise the possibility that aberrant regulation of IEGs including Junb and Arc may contribute to altered cocaine-induced neuronal and behavioral plasticity in Mecp2 mutant mice. C1 [Su, Dan; Cha, Young May; West, Anne E.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. NIEHS, Environm Genom Grp, Res Triangle Pk, NC 27709 USA. RP West, AE (reprint author), Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. EM west@neuro.duke.edu FU NIH [R01-DA022202] FX We thank A.N. Hutchinson, J.V. Deng and W.C. Wetsel for assistance with the animal experiments. This work was supported by NIH grant R01-DA022202 to A.E.W. NR 55 TC 7 Z9 7 U1 0 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD FEB PY 2012 VL 7 IS 2 BP 146 EP 154 DI 10.4161/epi.7.2.18907 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 890OR UT WOS:000300154600006 PM 22395464 ER PT J AU Shiao, YH Anderson, LM AF Shiao, Yih-Horng Anderson, Lucy M. TI Structural genomic changes during mammalian ontogeny: a new dimension SO EPIGENOMICS LA English DT Editorial Material DE DNA methylation; epigenetic; genome structure instability; LINE-1 elements; mammalian development; mosaicism; ontogeny; rDNA; tissue specificity ID RIBOSOMAL-RNA GENES; DNA TOPOISOMERASE-I; COMPLEX; CANCER; CELLS; EXPRESSION; NUCLEOLUS; TARGET; BRAIN C1 [Shiao, Yih-Horng; Anderson, Lucy M.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Anderson, LM (reprint author), NCI, Comparat Carcinogenesis Lab, Bldg 538,Room 205A,POB B, Frederick, MD 21702 USA. EM lmandersonphd@gmail.com FU Intramural NIH HHS NR 29 TC 0 Z9 0 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-1911 J9 EPIGENOMICS-UK JI Epigenomics PD FEB PY 2012 VL 4 IS 1 BP 1 EP 4 DI 10.2217/EPI.11.100 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 890FG UT WOS:000300129900001 PM 22332651 ER PT J AU Qi, QB Workalemahu, T Zhang, CL Hu, FB Qi, L AF Qi, Qibin Workalemahu, Tsegaselassie Zhang, Cuilin Hu, Frank B. Qi, Lu TI Genetic variants, plasma lipoprotein(a) levels, and risk of cardiovascular morbidity and mortality among two prospective cohorts of type 2 diabetes SO EUROPEAN HEART JOURNAL LA English DT Article DE Cardiovascular disease; Genome-wide association; Lipoprotein(a); Type 2 diabetes ID CORONARY-HEART-DISEASE; MIDDLE-AGED PATIENTS; ARTERY-DISEASE; ASSOCIATION ANALYSIS; LDL CHOLESTEROL; FOLLOW-UP; MELLITUS; WOMEN; INSULIN; STROKE AB Aims To examine the relations between genetic loci, plasma lipoprotein(a) [Lp(a)] levels, and cardiovascular disease (CVD) risk among diabetic patients and compare with the observations in the general population. Methods and results In two prospective cohorts of patients with type 2 diabetes (n = 2308) from the Nurses' Health Study and the Health Professional Follow-Up Study, we performed (i) genome-wide association (GWA) scans for plasma Lp(a); (ii) prospective analysis of plasma Lp(a) for CVD risk and mortality; and (iii) genetic association analysis for CVD risk and mortality. Meta-analysis of the two GWA scans yielded 71 single-nucleotide polymorphisms (SNPs) on chromosome 6q associated with plasma Lp(a) levels at a genome-wide significance level (P < 5 x 10(-8)). The SNP rs10455872 in LPA was most strongly associated with Lp(a) (P = 4.60 x 10(-39)). Forward-selection analysis indicated that rs10455872 and other five SNPs in a region encompassing LPA, PLG, SLC22A3, and LPAL2 genes were independently associated with Lp(a) levels and jointly explained similar to 20% of variation in diabetic patients. In prospective analysis, we did not find any significant association between plasma levels and CVD incidence; the relative risk for coronary heart disease (CHD), CVD, and CVD death was 1.05 [95% confidence interval (CI): 0.95-1.15], 1.05 (0.96-1.15), and 1.21 (0.99-1.47) per 1-SD higher log-transformed Lp(a) levels, respectively. Consistently, none of the Lp(a) SNPs were associated with CVD risk or mortality (all P > 0.09). For the best SNP rs10455872 for plasma Lp(a) levels, the OR for CHD, CVD, and CVD death was 0.94 (95% CI: 0.69-1.28), 0.97 (0.72-1.29), and 1.23 (0.79-1.92), respectively. The genetic effect on CHD risk showed a significant heterogeneity between the diabetic and the general populations (P = 0.006). Conclusion Our data indicate that the effect of Lp(a) on CVD risk among diabetic patients might be different from that in the general population. Diabetes status may attenuate the relation between Lp(a) and cardiovascular risk. C1 [Qi, Qibin; Workalemahu, Tsegaselassie; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hu, Frank B.; Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM nhlqi@channing.harvard.edu RI Qi, Qibin/H-9055-2012 FU National Institutes of Health [HL71981]; Boston Obesity Nutrition Research Center [DK46200]; American Heart Association [0730094N]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This study was supported by grant HL71981 from the National Institutes of Health, DK46200, from the Boston Obesity Nutrition Research Center. L.Q. was a recipient of the American Heart Association Scientist Development Award (0730094N). C.Z. was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 46 TC 36 Z9 37 U1 0 U2 9 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 325 EP 334 DI 10.1093/eurheartj/ehr350 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 889AO UT WOS:000300046100013 PM 21900290 ER PT J AU Steward, O Popovich, PG Dietrich, WD Kleitman, N AF Steward, Oswald Popovich, Phillip G. Dietrich, W. Dalton Kleitman, Naomi TI Replication and reproducibility in spinal cord injury research SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Replication; Regeneration ID NOGO-66 RECEPTOR ANTAGONIST; FUNCTIONAL RECOVERY; DELAYED TRANSPLANTATION; NEUROPROTECTIVE AGENT; REGENERATIVE GROWTH; CORTICOSPINAL TRACT; LOCOMOTOR RECOVERY; PROMOTES RECOVERY; AXON REGENERATION; IMPROVES RECOVERY AB This special issue of Experimental Neurology compiles a series of papers that either explicitly replicate published studies or retest phenomena reported in previous publications. The explicit replications were carried out as part of the "Facilities of Research Excellence-Spinal Cord Injury" (FORE-SCI) program launched by the National Institute of Neurological Disorders and Stroke (NINDS) in 2003. Here, we review the FORE-SCI replication experiments published prior to those in this special issue. We then discuss emerging issues regarding replication and reproducibility in spinal cord injury research, especially in terms of potential translation to clinical trials. (C) 2011 Elsevier Inc. All rights reserved. C1 [Steward, Oswald] Univ Calif Irvine, Reeve Irvine Res Ctr, Gillespie Neurosci Res Facil 1105, Sch Med, Irvine, CA 92697 USA. [Steward, Oswald] Univ Calif Irvine, Sch Med, Dept Anat & Neurobiol, Irvine, CA 92697 USA. [Steward, Oswald] Univ Calif Irvine, Sch Med, Dept Neurobiol & Behav, Irvine, CA 92697 USA. [Steward, Oswald] Univ Calif Irvine, Sch Med, Dept Neurosurg, Irvine, CA 92697 USA. [Popovich, Phillip G.] Ohio State Univ, Coll Med, Ctr Brain & Spinal Cord Repair, Columbus, OH USA. [Popovich, Phillip G.] Ohio State Univ, Coll Med, Dept Neurosci, Columbus, OH 43210 USA. [Dietrich, W. Dalton] Univ Miami, Leonard M Miller Sch Med, Miami Project Cure Paralysis, Miami, FL 33136 USA. [Dietrich, W. Dalton] Univ Miami, Leonard M Miller Sch Med, Dept Neurol Surg, Miami, FL 33136 USA. [Kleitman, Naomi] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. RP Steward, O (reprint author), Univ Calif Irvine, Reeve Irvine Res Ctr, Gillespie Neurosci Res Facil 1105, Sch Med, Irvine, CA 92697 USA. EM osteward@uci.edu OI Kleitman, Naomi/0000-0003-1089-0257; Steward, Oswald/0000-0001-7069-8756 FU [N01-NS-3-2353]; [HHSN271200800039C]; [HHSN271200800040C]; [N01-NS-3-2352] FX Supported by N01-NS-3-2353 and HHSN271200800039C (O.S.), HHSN271200800040C (P.G.P.), and N01-NS-3-2352 (W.D.D.). The authors gratefully acknowledge Ms. Laurie Leonard, who serves as Contracting Officer for the FORE-SCI contracts and Dr. Arlene Chiu, who initiated the NINDS FORE-SCI program. NR 48 TC 68 Z9 68 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 2012 VL 233 IS 2 SI SI BP 597 EP 605 DI 10.1016/j.expneurol.2011.06.017 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 890CV UT WOS:000300123600001 PM 22078756 ER PT J AU Huang, Y Ko, H Cheung, ZH Yung, KKL Yao, T Wang, JJ Morozov, A Ke, Y Ip, NY Yung, WH AF Huang, Ying Ko, Ho Cheung, Zelda H. Yung, Ken K. L. Yao, Tai Wang, Jian-Jun Morozov, Alexei Ke, Ya Ip, Nancy Y. Yung, Wing-Ho TI Dual actions of brain-derived neurotrophic factor on GABAergic transmission in cerebellar Purkinje neurons SO EXPERIMENTAL NEUROLOGY LA English DT Article DE BDNF; GABA(A); KCC2; Cdk5; Purkinje neurons ID CL-COTRANSPORTER KCC2; RAT VISUAL-CORTEX; SYNAPTIC-TRANSMISSION; DOWN-REGULATION; MESSENGER-RNAS; DORSAL-HORN; FACTOR BDNF; EXPRESSION; RECEPTORS; MODULATION AB The ability to regulate inhibitory synapses is a critical feature of the nervous system and a growing body of evidence indicates that brain-derived neurotrophic factor (BDNF) acutely modulates the efficacy of GABA synaptic transmission. Although the neuronal potassium-chloride cotransporter 2 (KCC2) has been implied in this BDNF-induced ionic plasticity, the reports about actions of BDNF on GABA signaling remain conflicting. Here we show dual effects of BDNF on GABAergic synaptic transmission in Purkinje neurons in rat cerebellar slices. BDNF decreased the amplitude of evoked outward IPSCs postsynaptically. It induced a depolarizing shift in the reversal potential (E-IPSC), which reduced the driving force for outward IPSCs. However, in the absence of KCC2 activity, BDNF directly potentiated rather than inhibited GABA(A) receptor, which was reflected by an increase in the amplitude of outward IPSCs. This action of BDNF coincided with its effect in increasing the amplitude of inward IPSCs. Furthermore, an interaction between GABA(A) receptor and KCC2 was revealed by co-immunoprecipitation. The effects of BDNF on both GABA(A) receptor and KCC2 were dependent on TrkB and also activation of cyclin-dependent kinase 5 (Cdk5). However, only the effect of BDNF on KCC2 activity was dependent on a rise of intracellular calcium. Taken together, these data highlight distinct actions of BDNF on KCC2 and GABA(A) receptor in the regulation of GABAergic synaptic transmission. (C) 2011 Elsevier Inc. All rights reserved. C1 [Huang, Ying; Yao, Tai] Fudan Univ, Dept Physiol & Pathophysiol, Shanghai Med Coll, Shanghai, Peoples R China. [Huang, Ying; Ko, Ho; Ke, Ya; Yung, Wing-Ho] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. [Cheung, Zelda H.; Ip, Nancy Y.] Hong Kong Univ Sci & Technol, Dept Biochem, Biotechnol Res Inst, Hong Kong, Hong Kong, Peoples R China. [Cheung, Zelda H.; Ip, Nancy Y.] Hong Kong Univ Sci & Technol, Mol Neurosci Ctr, Hong Kong, Hong Kong, Peoples R China. [Yung, Ken K. L.] Hong Kong Baptist Univ, Dept Biol, Kowloon Tong, Hong Kong, Peoples R China. [Wang, Jian-Jun] Nanjing Univ, Sch Life Sci, Dept Biol Sci & Technol, Nanjing, Jiangsu, Peoples R China. [Huang, Ying; Morozov, Alexei] NIMH, Unit Behav Genet, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Huang, Y (reprint author), Fudan Univ, Dept Physiol & Pathophysiol, Shanghai Med Coll, Shanghai, Peoples R China. EM yinghuang@shmu.edu.cn; whyung@cuhk.edu.hk RI Ko, Ho/I-7513-2016; OI Ko, Ho/0000-0002-0254-3274; Yung, Ken KL/0000-0002-9588-2573 FU Research Grants Council of Hong Kong [2900336]; NSFC/RGC from National Natural Science Foundation of China [30931160433] FX We thank Mr. Kenny Ho and Mr. Alan S.L. Wong for expert technical assistance. This work was supported by the Research Grants Council of Hong Kong (2900336) and the NSFC/RGC Joint Research Scheme 30931160433 from the National Natural Science Foundation of China. NR 47 TC 12 Z9 13 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 2012 VL 233 IS 2 SI SI BP 791 EP 798 DI 10.1016/j.expneurol.2011.11.043 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 890CV UT WOS:000300123600027 PM 22178325 ER PT J AU Rausch, M Lorch, S Chung, K Frederick, M Zhang, J Barnhart, K AF Rausch, Mary Lorch, Scott Chung, Karine Frederick, Margaret Zhang, Jun Barnhart, Kurt TI A cost-effectiveness analysis of surgical versus medical management of early pregnancy loss SO FERTILITY AND STERILITY LA English DT Article DE Cost-effectiveness analysis; early pregnancy loss; electric vacuum aspiration; manual vacuum aspiration; miscarriage; misoprostol ID RANDOMIZED CONTROLLED-TRIAL; MANUAL VACUUM ASPIRATION; QUALITY-OF-LIFE; 1ST-TRIMESTER MISCARRIAGE; INCOMPLETE MISCARRIAGE; EXPECTANT MANAGEMENT; SPONTANEOUS-ABORTION; ECONOMIC-EVALUATION; CLINICAL-TRIAL; MIST TRIAL AB Objective: To determine the cost-effectiveness of medical and surgical management of early pregnancy loss. Design: Analyses of cost, effectiveness, and incremental cost-effectiveness ratios and utilities of a multicenter trial with 652 women with first-trimester pregnancy failure randomized to medical or surgical management. Setting: Analysis of data from a multicenter trial. Patient(s): Secondary analysis of a multicenter trial. Intervention(s): Cost-effectiveness analysis. Main Outcome Measure(s): Cost and effectiveness of competing treatment strategies. Result(s): Cost analysis of treatment demonstrates an increased cost of US$336 for 13% increased efficacy of surgical management. This analysis was sensitive to the probability of an extra office visit, the cost of the visit, and the probability of success. When the surgical arm is divided into outpatient manual vacuum aspiration (MVA) versus inpatient electric vacuum aspiration (EVA), there is an increased cost of $745 for EVA but a decreased cost of $202 for MVA compared with medical management. In general, MVA was found to be more cost-effective than medical management. For treatment of incomplete or inevitable abortion, medical management was found to be less costly and more efficacious. Utilities studies demonstrated that a patient would need to prefer surgery 14% less than medication for its treatment efficacy to be outweighed by the desire to avoid surgery. Conclusion(s): Surgical or medical management of early pregnancy failure can be cost effective, depending on the circumstances. Surgery is cost effective and more efficacious when performed in an outpatient setting. For incomplete or inevitable abortion, medical management is cost effective and more efficacious. (Fertil Steril (R) 2012;97:355-60. (C)2012 by American Society for Reproductive Medicine.) C1 [Barnhart, Kurt] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Rausch, Mary] N Shore Univ Hosp, Manhasset, NY USA. [Lorch, Scott] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Chung, Karine] Univ So Calif, Los Angeles, CA USA. [Frederick, Margaret] Clinical Trials & Surveys Corp, Owings Mills, MD USA. [Zhang, Jun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Barnhart, K (reprint author), Univ Penn, Med Ctr, 3701 Market St,Suite 800, Philadelphia, PA 19104 USA. EM kbarnhart@obgyn.upenn.edu FU National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services [N01-HD-1-3321, N01-HD-1-3322, N01-HD-1-3323, N01-HD-1-3324, N01-HD-1-3325, R01-HD036455, K24HD060687, T32-HD007440] FX Funded by the National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services under Contract Numbers: N01-HD-1-3321 through 3325 with additional support from R01-HD036455 (K.B.), K24HD060687 (K.B.), and T32-HD007440 (M.R.). NR 22 TC 23 Z9 23 U1 2 U2 8 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 355 EP U379 DI 10.1016/j.fertnstert.2011.11.044 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 887WG UT WOS:000299961800021 PM 22192348 ER PT J AU Schaefer, GO Sinaii, N Grady, C AF Schaefer, Gerald Owen Sinaii, Ninet Grady, Christine TI Informing egg donors of the potential for embryonic research: a survey of consent forms from US in vitro fertilization clinics SO FERTILITY AND STERILITY LA English DT Article DE Informed consent; oocyte donors; research ID STEM-CELL RESEARCH AB Objective: To understand whether and to what extent U.S. IVF clinics inform egg donors that resultant embryos initially intended to be implanted for reproductive purposes may in fact be used for research instead. Design: Four hundred seventy U. S. IVF clinics were asked to respond to a questionnaire and provide a copy of the egg donor consent form(s) used at the clinic. Setting: Four hundred seventy U. S. IVF clinics listed in a Centers for Disease Control and Prevention database; only forms from clinics that both accepted donor eggs and provided excess embryos for research were analyzed for content. Patient(s): Not applicable. Intervention(s): Not applicable. Main Outcome Measure(s): Responses to the questionnaire, demographic data from a Centers for Disease Control and Prevention database, and the content of egg donor consent forms. Result(s): Of 222 U. S. IVF clinics that responded to our query, 100 clinics both accepted donor eggs and provided some excess embryos for research. We received 66 consent forms from these 100 clinics, which showed that although most egg donor consent forms inform donors that they will not have control over embryos resulting from their eggs, 30% inform them that some embryos may be used for research, and even fewer mention stem cell research. Conclusion(s): Egg donors in the United States, including some who may have a moral objection to research and stem cell research, are not being informed that embryos created with their donated eggs may in fact be used for these purposes. This can be corrected with the inclusion of succinct, nontechnical language in egg donor consent forms. (Fertil Steril(R) 2012;97:427-33. (C) 2012 by American Society for Reproductive Medicine.) C1 [Schaefer, Gerald Owen; Grady, Christine] Natl Inst Hlth Clin Ctr, Dept Bioeth, Bethesda, MD 20892 USA. [Schaefer, Gerald Owen] Univ Oxford, St Cross Coll, Fac Philosophy, Oxford, England. [Sinaii, Ninet] Natl Inst Hlth Clin Ctr, Biostat & Clin Epidemiol Serv, Bethesda, MD USA. RP Grady, C (reprint author), Natl Inst Hlth Clin Ctr, Dept Bioeth, Bldg 10-1C118, Bethesda, MD 20892 USA. EM cgrady@nih.gov OI Schaefer, Gerald Owen/0000-0002-6915-6148 FU National Institutes of Health Clinical Center FX Funding and support for design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript were provided by the National Institutes of Health Clinical Center. NR 13 TC 5 Z9 5 U1 0 U2 7 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 427 EP 433 DI 10.1016/j.fertnstert.2011.11.035 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 887WG UT WOS:000299961800033 PM 22196714 ER PT J AU Rothenberg, KH Bush, LW AF Rothenberg, Karen H. Bush, Lynn W. TI Genes and plays: bringing ELSI issues to life SO GENETICS IN MEDICINE LA English DT Article DE ELSI; genetics; genomic research; plays; vignettes ID MEDICAL-EDUCATION; CLINICAL-PRACTICE; PERFORMANCE; STUDENTS; ETHICS; DRAMA; TIME; WIT AB Ethical complexities surround the promise of genomic technology and the power of genetic information as they alter conceptions of identity and dynamics within personal and professional relationships. Creative approaches such as dramatic vignettes offer a unique analytical stage for imagining the bioethical past and future. Dramatic narratives can bring to life images of differing perspectives and values when experiencing innovations in medicine. Although the scientific landscape shifts, concerns expressed in theatre from 50 years ago parallel many contemporary ELSI (ethical, legal, and social implications) issues, highlighting the ongoing struggle to appreciate the impact of emerging genetic technologies on relationships. To illuminate these enduring concerns, we explore how perceptions and relationships have influenced and been influenced by genetics as portrayed through dramatic vignettes. We build on the legacy of using case vignettes as a clinical teaching modality, and believe similar value exists within the research ethics domain. The selection of dialogue discussed encompasses abbreviated excerpts from two existing and one original vignette that we staged at the ELSI 2011 Congress and various academic and health institutions. Genet Med 2012:14(2):274-277 C1 [Rothenberg, Karen H.] Univ Maryland Francis King Carey Sch Law, Baltimore, MD USA. [Rothenberg, Karen H.] NHGRI, Dept Bioeth, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Bush, Lynn W.] Columbia Univ, Dept Clin Genet, New York, NY USA. RP Rothenberg, KH (reprint author), Univ Maryland Francis King Carey Sch Law, Baltimore, MD USA. EM krothenberg@law.umaryland.edu NR 34 TC 0 Z9 1 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD FEB PY 2012 VL 14 IS 2 BP 274 EP 277 DI 10.1038/gim.2011.47 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 890BI UT WOS:000300119700014 PM 22241098 ER PT J AU Heidari, S Mofenson, LM Hobbs, CV Cotton, MF Marlink, R Katabira, E AF Heidari, Shirin Mofenson, Lynne M. Hobbs, Charlotte V. Cotton, Mark F. Marlink, Richard Katabira, Elly TI Unresolved Antiretroviral Treatment Management Issues in HIV-Infected Children SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Review DE antiretroviral; childhood growth and development; drug complications; HIV-infected infants; malaria; malnutrition; tuberculosis ID RECONSTITUTION INFLAMMATORY SYNDROME; PLASMODIUM-FALCIPARUM MALARIA; BONE-MINERAL DENSITY; IMMUNODEFICIENCY-VIRUS-INFECTION; TENOFOVIR DISOPROXIL FUMARATE; OPTIMIZED BACKGROUND REGIMEN; SOUTH-AFRICAN CHILDREN; SUB-SAHARAN AFRICA; UNINFECTED CHILDREN; COTRIMOXAZOLE PROPHYLAXIS AB Antiretroviral therapy in children has expanded dramatically in low-income and middle-income countries. The World Health Organization revised its pediatric HIV guidelines to recommend initiation of antiretroviral therapy in all HIV-infected children younger than 2 years, regardless of CD4 count or clinical stage. The number of children starting life-long antiretroviral therapy should therefore expand dramatically over time. The early initiation of antiretroviral therapy has indisputable benefits for children, but there is a paucity of definitive information on the potential adverse effects. In this review, a comprehensive literature search was conducted to provide an overview of our knowledge about the complications of treating pediatric HIV. Antiretroviral therapy in children, as in adults, is associated with enhanced survival, reduction in opportunistic infections, improved growth and neurocognitive function, and better quality of life. Despite antiretroviral therapy, HIV-infected children may continue to lag behind their uninfected peers in growth and development. In addition, epidemic concurrent conditions, such as tuberculosis, malaria, and malnutrition, can combine with HIV to yield more rapid disease progression and poor treatment outcomes. Additional studies are required to evaluate the long-term effects of antiretroviral therapy in HIV-infected infants, children, and adolescents, particularly in resource-limited countries where concomitant infections and conditions may enhance the risk of adverse effects. There is an urgent need to evaluate drug-drug interactions in children to determine optimal treatment regimens for both HIV and coinfections. C1 [Heidari, Shirin] Int AIDS Soc, Dept Res Promot, CH-1216 Geneva, Switzerland. [Mofenson, Lynne M.] NIH, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. [Hobbs, Charlotte V.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA. [Cotton, Mark F.] Univ Stellenbosch, Dept Pediat & Child Hlth, ZA-7600 Stellenbosch, South Africa. [Cotton, Mark F.] Tygerberg Childrens Hosp, Tygerberg, South Africa. [Marlink, Richard] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Marlink, Richard] Elizabeth Glaser Pediat AIDS Fdn, Los Angeles, CA USA. [Katabira, Elly] Makerere Univ, Coll Hlth Sci, Kampala, Uganda. RP Heidari, S (reprint author), Int AIDS Soc, Dept Res Promot, 71 Ave Louis Casai, CH-1216 Geneva, Switzerland. EM shirin.heidar-i@iasociety.org OI Mofenson, Lynne/0000-0002-2818-9808 FU Abbott; Boehringer Ingelheim; Gilead; Merck; Pfizer; Tibotec; ViiV Healthcare; International AIDS Society FX The mapping exercise was financially supported by unrestricted educational grants from Abbott, Boehringer Ingelheim, Gilead, Merck, Pfizer, Tibotec and ViiV Healthcare, and the International AIDS Society.; The authors S. H. is an employee of the International AIDS Society, and her salary is provided partly by unrestricted educational grants from the following pharmaceutical companies: Abbott, Boehringer Ingelheim, Gilead, Merck, Pfizer, Tibotec and ViiV Healthcare. M. F. C. is an investigator on GSK and Boehringer Ingelheim trials and has received honoraria from Abbott and GSK within the past 6 months. R. M. has served as an advisor to the BMS Foundation and the Merck Company Foundation. L. M. M., C. V. H., and E. K. have no competing interests. NR 101 TC 16 Z9 16 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB 1 PY 2012 VL 59 IS 2 BP 161 EP 169 DI 10.1097/QAI.0b013e3182427029 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 885OX UT WOS:000299789600014 PM 22138766 ER PT J AU Hirano, Y Suzuki, T Matsumoto, T Ishihara, Y Takaki, Y Kono, M Dohmae, N Tsuji, S AF Hirano, Yuichi Suzuki, Takehiro Matsumoto, Takumi Ishihara, Yoshimi Takaki, Yoshie Kono, Mari Dohmae, Naoshi Tsuji, Shuichi TI Disulphide linkage in mouse ST6Gal-I: determination of linkage positions and mutant analysis SO JOURNAL OF BIOCHEMISTRY LA English DT Article ID POLYMERASE-CHAIN-REACTION; CLONING; SIALYLTRANSFERASES; PROTEINS; LOCALIZATION; EXPRESSION; MECHANISM; RESIDUES; DONOR AB All cloned sialyltransferases from vertebrates are classified into four subfamilies and are characterized as having type II transmembrane topology. The catalytic domain has highly conserved motifs known as sialylmotifs. Besides sialylmotifs, each family has several unique conserved cysteine (Cys) residues mainly in the catalytic domain. The number and loci of conserved amino acids, however, differ with each subfamily, suggesting that the conserved Cys-residues and/or disulphide linkages they make may contribute to linkage specificity. Using Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF)-mass spectrometry, the present study performed disulphide linkage analysis on soluble mouse ST6Gal-I, which has six Cys-residues. Results confirmed that there were no free Cys-residues, and all six residues contributed to disulphide linkage formation, C-139-C-403, C-181-C-332 and C-350-C-361. Study of single amino acid-substituted mutants revealed that the disulphide linkage C-181-C-332 was necessary for molecular expression of the enzyme, and that the disulphide linkage C-350-C-361 was necessary for enzyme activity. The remaining disulphide linkage C-139-C-403 was not necessary for enzyme expression or for activity, including substrate specificity. Crystallographic study of pig ST3Gal I has recently been reported. Interestingly, the loci of disulphide linkages in ST6Gal-I differ from those in ST3Gal I, suggesting that the linkage specificity of sialyltransferase may results from significant structural differences, including the loci of disulphide linkages. C1 [Hirano, Yuichi; Matsumoto, Takumi; Takaki, Yoshie; Tsuji, Shuichi] Tokai Univ, Inst Glycosci, Hiratsuka, Kanagawa 2591292, Japan. [Hirano, Yuichi; Ishihara, Yoshimi] RIKEN Adv Sci Inst, Biomol Characterizat Team, Wako, Saitama 3510198, Japan. [Suzuki, Takehiro; Dohmae, Naoshi] Tokai Univ, Dept Chem, Sch Sci, Hiratsuka, Kanagawa 2591292, Japan. [Kono, Mari] NIH, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. RP Tsuji, S (reprint author), Tokai Univ, Inst Glycosci, 4-1-1 Kitakaname, Hiratsuka, Kanagawa 2591292, Japan. EM stsuji@tokai-u.jp RI Dohmae, Naoshi/C-2040-2011 NR 17 TC 5 Z9 6 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0021-924X J9 J BIOCHEM JI J. Biochem. PD FEB PY 2012 VL 151 IS 2 BP 197 EP 203 DI 10.1093/jb/mvr133 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 885NZ UT WOS:000299787000010 PM 22039275 ER PT J AU Reinholdt-Dunne, ML Mogg, K Benson, V Bradley, BP Hardin, MG Liversedge, SP Pine, DS Ernsts, M AF Reinholdt-Dunne, M. L. Mogg, K. Benson, V. Bradley, B. P. Hardin, M. G. Liversedge, S. P. Pine, D. S. Ernsts, M. TI Anxiety and selective attention to angry faces: An antisaccade study SO JOURNAL OF COGNITIVE PSYCHOLOGY LA English DT Article DE Angry faces; Antisaccade; Anxiety; Selective attention ID COGNITIVE CONTROL; DEPRESSED ADOLESCENTS; TASK; PSYCHOPATHOLOGY; PROSACCADES; PERFORMANCE; INHIBITION; EFFICIENCY; ACCOUNT; SCALES AB Cognitive models of anxiety propose that anxiety is associated with an attentional bias for threat, which increases vulnerability to emotional distress and is difficult to control. The study aim was to investigate relationships between the effects of threatening information, anxiety, and attention control on eye movements. High and low trait anxious individuals performed antisaccade and prosaccade tasks with angry, fearful, happy, and neutral faces. Results indicated that high-anxious participants showed a greater antisaccade cost for angry than neutral faces (i.e., relatively slower to look away from angry faces), compared with low-anxious individuals. This bias was not found for fearful or happy faces. The bias for angry faces was not related to individual differences in attention control assessed on self-report and behavioural measures. Findings support the view that anxiety is associated with difficulty in using cognitive control resources to inhibit attentional orienting to angry faces, and that attention control is multifaceted. C1 [Reinholdt-Dunne, M. L.; Mogg, K.; Benson, V.; Bradley, B. P.; Liversedge, S. P.] Univ Southampton, Sch Psychol, Southampton SO17 1BJ, Hants, England. [Reinholdt-Dunne, M. L.] Univ Copenhagen, Dept Psychol, Copenhagen, Denmark. [Hardin, M. G.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. [Pine, D. S.; Ernsts, M.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. RP Mogg, K (reprint author), Univ Southampton, Sch Psychol, Southampton SO17 1BJ, Hants, England. EM kmogg@soton.ac.uk RI Bradley, Brendan/B-9724-2008; Mogg, Karin/C-1181-2008; OI Mogg, Karin/0000-0002-2738-7378; Bradley, Brendan/0000-0003-2801-4271 NR 34 TC 12 Z9 12 U1 3 U2 22 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 2044-5911 J9 J COGN PSYCHOL JI J. Cogn. Psychol. PD FEB PY 2012 VL 24 IS 1 SI SI BP 54 EP 65 DI 10.1080/20445911.2011.560111 PG 12 WC Psychology, Experimental SC Psychology GA 887HK UT WOS:000299917300005 ER PT J AU Hingson, RW Heeren, T Edwards, EM Saitz, R AF Hingson, Ralph W. Heeren, Timothy Edwards, Erika M. Saitz, Richard TI Young Adults at Risk for Excess Alcohol Consumption Are Often Not Asked or Counseled About Drinking Alcohol SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE alcoholism and addictive behavior; communication; patient education; prevention ID UNITED-STATES; NATIONAL-SURVEY; IDENTIFICATION; INTERVENTION; DEPENDENCE; DISEASE AB Excessive alcohol consumption is most widespread among young adults. Practice guidelines recommend screening and physician advice, which could help address this common cause of injury and premature death. To assess the proportion of persons ages 18-39 who, in the past year, saw a physician and were asked about their drinking and advised what drinking levels pose health risk, and whether this differed by age or whether respondents exceeded low-risk drinking guidelines [daily (> 4 drinks for men/> 3 for women) or weekly (> 14 for men/> 7 for women)]. Survey of young adults selected from a national internet panel established using random digit dial telephone techniques. Adults age 18-39 who ever drank alcohol, n = 3,409 from the internet panel and n = 612 non-panel telephone respondents. Respondents were asked whether they saw a doctor in the past year; those who did see a doctor were asked whether a doctor asked about their drinking, advised about safe drinking levels, or counseled to reduce drinking. Of respondents, 67% saw a physician in the past year, but only 14% of those exceeding guidelines were asked and advised about risky drinking patterns. Persons 18-25 were the most likely to exceed guidelines (68% vs. 56%, p < 0.001) but were least often asked about drinking (34% vs. 54%, p < 0.001). Despite practice guidelines, few young adults are asked and advised by physicians about excessive alcohol consumption. Physicians should routinely ask all adults about their drinking and offer advice about levels that pose health risk, particularly to young adults. C1 [Hingson, Ralph W.] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA. [Heeren, Timothy; Edwards, Erika M.; Saitz, Richard] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Saitz, Richard] Boston Med Ctr, Clin Addict Res & Educ CARE Unit, Sect Gen Internal Med, Boston, MA USA. RP Hingson, RW (reprint author), NIAAA, Div Epidemiol & Prevent Res, 5635 Fishers Lane,Room 2077, Bethesda, MD 20892 USA. EM rhingson@mail.nih.gov OI Heeren, Timothy/0000-0001-5643-3559; /0000-0002-2535-1427 FU National Institute on Alcohol Abuse; Alcoholism Center [P60AA13759]; National Institutes of Health (NIH); University of Massachusetts; Brandeis University FX This article is dedicated to Helen Marie Witty, who at age 16 was fatally injured by a young alcohol-impaired driver. Dr. Ralph Hingson 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. This study was supported in part by the National Institute on Alcohol Abuse and Alcoholism Center Grant P60AA13759.; Drs. Ralph Hingson, Tim Heeren, and Erika Edwards have no conflicts of interest to report. Dr. Richard Saitz reports having been a consultant for online alcohol-related screening and brief intervention education projects supported by National Institutes of Health (NIH) grants to Medical Directions and Inflexxion and for NIH grants to the RAND corporation, Kaiser Permanente, the University of Massachusetts, and Brandeis University. Dr. Saitz also has been compensated by Beth Israel Deaconess Hospital and the National Institute on Alcohol Abuse and Alcoholism for serving on data and safety monitoring boards. He is compensated for educational work by the Massachusetts Medical Society, the British Medical Journal Group, and the American Society of Addiction Medicine. He has developed educational materials for Fusion medical education and consulted for Saatchi and Saatchi Healthcare on alcohol dependence treatment. He has or anticipates being compensated as a speaker on alcohol and drug topics by multiple government agencies, academic institutions, and professional societies. He has also provided expert opinion on legal cases involving identification and management of alcohol and drug related problems. NR 35 TC 24 Z9 24 U1 0 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 179 EP 184 DI 10.1007/s11606-011-1851-1 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 889HS UT WOS:000300064900012 PM 21935753 ER PT J AU Cook, S Moureau, G Kitchen, A Gould, EA de Lamballerie, X Holmes, EC Harbachl, RE AF Cook, Shelley Moureau, Gregory Kitchen, Andrew Gould, Ernest A. de Lamballerie, Xavier Holmes, Edward C. Harbachl, Ralph E. TI Molecular evolution of the insect-specific flaviviruses SO JOURNAL OF GENERAL VIROLOGY LA English DT Review ID NATURAL MOSQUITO POPULATION; MULTIPLE SEQUENCE ALIGNMENT; AEDES-ALBOPICTUS CELLS; FUSING AGENT VIRUS; GENUS FLAVIVIRUS; PHYLOGENETIC-RELATIONSHIPS; DIPTERA-CULICIDAE; YUCATAN PENINSULA; BORNE VIRUSES; RNA VIRUSES AB There has been an explosion in the discovery of 'insect-specific' flaviviruses and/or their related sequences in natural mosquito populations. Herein we review all 'insect-specific' flavivirus sequences currently available and conduct phylogenetic analyses of both the 'insect-specific' flaviviruses and available sequences of the entire genus Flavivirus. We show that there is no statistical support for virus mosquito co-divergence, suggesting that the 'insect-specific' flaviviruses may have undergone multiple introductions with frequent host switching. We discuss potential implications for the evolution of vectoring within the family Flaviviridae. We also provide preliminary evidence for potential recombination events in the history of cell fusing agent virus. Finally, we consider priorities and guidelines for future research on 'insect-specific' flaviviruses, including the vast potential that exists for the study of biodiversity within a range of potential hosts and vectors, and its effect on the emergence and maintenance of the flaviviruses. C1 [Cook, Shelley; Harbachl, Ralph E.] Nat Hist Museum, London SW7 5BD, England. [Moureau, Gregory; Gould, Ernest A.; de Lamballerie, Xavier] Univ Aix Marseille 2, Inst Rech Dev, EHESP French Sch Publ Hlth, Unite Virus Emergents UMR190, Marseille, France. [Kitchen, Andrew; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Gould, Ernest A.] Ctr Ecol & Hydrol, Wallingford OX10 8BB, Oxon, England. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Cook, S (reprint author), Nat Hist Museum, Cromwell Rd, London SW7 5BD, England. EM s.cook@nhm.ac.uk OI Holmes, Edward/0000-0001-9596-3552 FU Wellcome Trust [039833] FX The work of S. C. is funded by a Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust (grant 039833). NR 57 TC 75 Z9 77 U1 3 U2 21 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD FEB PY 2012 VL 93 BP 223 EP 234 DI 10.1099/vir.0.036525-0 PN 2 PG 12 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 890IY UT WOS:000300139500001 PM 22012464 ER PT J AU Harbison, CE Weichert, WS Gurda, BL Chiorini, JA Agbandje-McKenna, M Parrish, CR AF Harbison, Carole E. Weichert, Wendy S. Gurda, Brittney L. Chiorini, John A. Agbandje-McKenna, Mavis Parrish, Colin R. TI Examining the cross-reactivity and neutralization mechanisms of a panel of mAbs against adeno-associated virus serotypes 1 and 5 SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; GENE-THERAPY VECTOR; MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSES; MEDIATED NEUTRALIZATION; TRANSGENE EXPRESSION; CANINE PARVOVIRUS; VIRAL VECTORS; SIALIC-ACID; IN-VITRO AB Neutralizing antibodies play a central role in the prevention and clearance of viral infections, but can be detrimental to the use of viral capsids for gene delivery. Antibodies present a major hurdle for ongoing clinical trials using adeno-associated viruses (AAVs); however, relatively little is known about the antigenic epitopes of most AAV serotypes or the mechanism(s) of antibody-mediated neutralization. We developed panels of AAV mAbs by repeatedly immunizing mice with AAV serotype 1 (AAV1) capsids, or by sequentially immunizing with AAV1 followed by AAV5 capsids, in order to examine the efficiency and mechanisms of antibody-mediated neutralization. The antibodies were not cross-reactive between heterologous AAV serotypes except for a low level of recognition of AAV1 capsids by the AAV5 antibodies, probably due to the initial immunization with AAV1. The neutralization efficiency of different IgGs varied and Fab fragments derived from these antibodies were generally poorly neutralizing. The antibodies appeared to display various alternative mechanisms of neutralization, which included inhibition of receptor-binding and interference with a post-attachment step. C1 [Harbison, Carole E.; Weichert, Wendy S.; Parrish, Colin R.] Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Baker Inst Anim Hlth, Ithaca, NY 14853 USA. [Gurda, Brittney L.; Agbandje-McKenna, Mavis] Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. [Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA. RP Parrish, CR (reprint author), Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Baker Inst Anim Hlth, Ithaca, NY 14853 USA. EM crp3@cornell.edu OI Gurda, Brittney /0000-0002-0174-9385 FU National Institutes of Allergy and Infectious Diseases [R21AI072341] FX Supported by National Institutes of Allergy and Infectious Diseases, grant R21AI072341. The authors would like to thank Sandra Wainer and Beverly Handleman for excellent technical support. NR 72 TC 14 Z9 14 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD FEB PY 2012 VL 93 BP 347 EP 355 DI 10.1099/vir.0.035113-0 PN 2 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 890IY UT WOS:000300139500014 PM 22071509 ER PT J AU Peden, AH McGuire, LI Appleford, NEJ Mallinson, G Wilham, JM Orru, CD Caughey, B Ironside, JW Knight, RS Will, RG Green, AJE Head, MW AF Peden, Alexander H. McGuire, Lynne I. Appleford, Nigel E. J. Mallinson, Gary Wilham, Jason M. Orru, Christina D. Caughey, Byron Ironside, James W. Knight, Richard S. Will, Robert G. Green, Alison J. E. Head, Mark W. TI Sensitive and specific detection of sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID IN-VITRO AMPLIFICATION; BLOOD-TRANSFUSION; SEEDED CONVERSION; PRPSC; TRANSMISSION; CLASSIFICATION; DIAGNOSIS; STRAINS; PATIENT; ASSAY AB Real-time quaking-induced conversion (RT-QuIC) is an assay in which disease-associated prion protein (PrP) initiates a rapid conformational transition in recombinant PrP (recPrP), resulting in the formation of amyloid that can be monitored in real time using the dye thioflavin T. It therefore has potential advantages over analogous cell-free PrP conversion assays such as protein misfolding cyclic amplification (PMCA). The QuIC assay and the related amyloid seeding assay have been developed largely using rodent-passaged sheep scrapie strains. Given the potential RT-QuIC has for Creutzfeldt-Jakob disease (CJD) research and human prion test development, this study characterized the behaviour of a range of CJD brain specimens with hamster and human recPrP in the RT-QuIC assay. The results showed that RT-QuIC is a rapid, sensitive and specific test for the form of abnormal PrP found in the most commonly occurring forms of sporadic CJD. The assay appeared to be largely independent of species-related sequence differences between human and hamster recPrP and of the methionine/valine polymorphism at codon 129 of the human PrP gene. However, with the same conditions and substrate, the assay was less efficient in detecting the abnormal PrP that characterizes variant CJD brain. Comparison of these QuIC results with those previously obtained using PMCA suggested that these two seemingly similar assays differ in important respects. C1 [Peden, Alexander H.; McGuire, Lynne I.; Ironside, James W.; Knight, Richard S.; Will, Robert G.; Green, Alison J. E.; Head, Mark W.] Univ Edinburgh, Sch Mol & Clin Med, Natl CJD Res & Surveillance Unit, Edinburgh, Midlothian, Scotland. [Appleford, Nigel E. J.; Mallinson, Gary] Bristol Inst Transfus Sci, Natl Blood Serv, Bristol, Avon, England. [Wilham, Jason M.; Orru, Christina D.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT USA. RP Head, MW (reprint author), Univ Edinburgh, Sch Mol & Clin Med, Natl CJD Res & Surveillance Unit, Edinburgh, Midlothian, Scotland. EM m.w.head@ed.ac.uk OI Head, Mark/0000-0003-2034-8613; Ironside, James/0000-0001-5869-2108 FU Scottish Government Health Directorates Chief Scientist Office [CZB/4/688]; Alliance BioSecure; National Institute of Allergy and Infectious Diseases, National Institutes of Health; MRC (UK); NCJDRSU; Department of Health, UK; Scottish Government FX This work was funded by grants from the Scottish Government Health Directorates Chief Scientist Office (CZB/4/688) to M. W. H. and from Alliance BioSecure to A. J. E. G. This work was also supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The National CJD Surveillance Unit Brain and Tissue Bank is supported by the MRC (UK), and the NCJDRSU as a whole is funded by the Department of Health, UK, and the Scottish Government. The views expressed in the publication are those of the authors and not necessarily those of the Department of Health, UK. The authors would like to thank the patients and their relatives for the opportunity to conduct research on tissue specimens. NR 36 TC 39 Z9 39 U1 1 U2 9 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD FEB PY 2012 VL 93 BP 438 EP 449 DI 10.1099/vir.0.033365-0 PN 2 PG 12 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 890IY UT WOS:000300139500024 PM 22031526 ER PT J AU Hirvonen, J Kreisl, WC Fujita, M Dustin, I Khan, O Appel, S Zhang, Y Morse, C Pike, VW Innis, RB Theodore, WH AF Hirvonen, Jussi Kreisl, William C. Fujita, Masahiro Dustin, Irene Khan, Omar Appel, Shmuel Zhang, Yi Morse, Cheryl Pike, Victor W. Innis, Robert B. Theodore, William H. TI Increased In Vivo Expression of an Inflammatory Marker in Temporal Lobe Epilepsy SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE positron emission tomography; translocator protein 18 kDa; epilepsy; inflammation ID PERIPHERAL BENZODIAZEPINE-RECEPTORS; POSITRON-EMISSION-TOMOGRAPHY; PROTEIN 18 KDA; TRANSLOCATOR PROTEIN; HUMAN BRAIN; HIPPOCAMPAL SCLEROSIS; PET; ENCEPHALITIS; ASSOCIATION; MICROGLIA AB Animal studies and clinical observations suggest that epilepsy is associated with inflammation. Translocator protein (TSPO) (18 kDa), a marker of inflammation, is increased in vitro in surgical samples from patients with temporal lobe epilepsy. TSPO can be measured in the living human brain with PET and the novel radioligand C-11-PBR28. In this study, we sought to determine whether in vivo expression of TSPO is increased ipsilateral to the seizure focus in patients with temporal lobe epilepsy. Methods: Sixteen patients with unilateral temporal lobe epilepsy and 30 healthy subjects were studied with C-11-PBR28 PET and MRI. Uptake of radioactivity after injection of C-11-PBR28 was measured from regions of interest drawn bilaterally onto MR images. Brain uptake from ipsilateral and contralateral hemispheres was compared using a paired-samples t test. Results: We found that brain uptake was higher ipsilateral to the seizure focus in the hippocampus, parahippocampal gyrus, amygdala, fusiform gyrus, and choroid plexus but not in other brain regions. This asymmetry was more pronounced in patients with hippocampal sclerosis than in those without. Conclusion: We found increased uptake of radioactivity after injection of C-11-PBR28 ipsilateral to the seizure focus in patients with temporal lobe epilepsy, suggesting increased expression of TSPO. Studies in larger samples are required to confirm this finding and determine the clinical utility of imaging TSPO in temporal lobe epilepsy. C1 [Hirvonen, Jussi; Kreisl, William C.; Fujita, Masahiro; Zhang, Yi; Morse, Cheryl; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Dustin, Irene; Khan, Omar; Appel, Shmuel; Theodore, William H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr,MSC 1026,Bldg 10,Room B1D43, Bethesda, MD 20892 USA. EM robert.innis@nih.gov FU National Institute of Mental Health [Z01-MH-002852-04]; National Institute of Neurological Disorders and Stroke [1Z01-NS002236-34]; Academy of Finland; Finnish Cultural Foundation; Finnish Foundation for Alcohol Studies; Finnish Medical Foundation; Instrumentarium Foundation; Jalmari and Rauha Ahokas Foundation; Paulo Foundation; Research Foundation of Orion Corporation; Yrjo Jahnsson Foundation FX We thank Desiree Ferraris Araneta and the PET Department in the Clinical Center for the successful completion of this research. We also thank Drs. Ruben Kuzniecky and Jacqueline French for referring patients. This work was supported by the intramural programs of the National Institute of Mental Health (project Z01-MH-002852-04) and the National Institute of Neurological Disorders and Stroke (project 1Z01-NS002236-34) and grants from the Academy of Finland, the Finnish Cultural Foundation, the Finnish Foundation for Alcohol Studies, the Finnish Medical Foundation, the Instrumentarium Foundation, the Jalmari and Rauha Ahokas Foundation, the Paulo Foundation, the Research Foundation of Orion Corporation, and the Yrjo Jahnsson Foundation. No other potential conflict of interest relevant to this article was reported. NR 29 TC 34 Z9 34 U1 0 U2 7 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB PY 2012 VL 53 IS 2 BP 234 EP 240 DI 10.2967/jnumed.111.091694 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 888VN UT WOS:000300032800014 PM 22238156 ER PT J AU Mirabelli, MC London, SJ Charles, LE Pompeii, LA Wagenknecht, LE AF Mirabelli, Maria C. London, Stephanie J. Charles, Luenda E. Pompeii, Lisa A. Wagenknecht, Lynne E. TI Occupation and the Prevalence of Respiratory Health Symptoms and Conditions The Atherosclerosis Risk in Communities Study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; WORK-RELATED ASTHMA; CHRONIC-BRONCHITIS; CLEANING WORKERS; ONSET ASTHMA; POPULATION; EXPOSURE; BURDEN; ADULTS; DUST AB Objectives: To examine associations between occupation and respiratory health in a large, population-based cohort of adults in the United States. Methods: Data from 15,273 participants, aged 45 to 64 years, in the Atherosclerosis Risk in Communities study were used to examine associations of current or most recent job held with the prevalence of self-reported chronic cough, chronic bronchitis, wheezing, asthma, and measures of lung function collected by spirometry. Results: Eleven percent of participants reported wheezing and 9% were classified as having airway obstruction. Compared with individuals in managerial and administrative jobs, increased prevalences of respiratory outcomes were observed among participants in selected occupations, including construction and extractive trades (wheezing, prevalence ratio = 1.92, 95% confidence interval = 1.35, 2.73; airway obstruction, prevalence ratio = 1.31, 95% confidence interval = 1.05, 1.65). Conclusions: Specific occupations are associated with adverse respiratory health. C1 [Mirabelli, Maria C.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [London, Stephanie J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Charles, Luenda E.] NIOSH, Biostat & Epidemiol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent,Dept Hlth & Human Serv, Morgantown, WV USA. [Pompeii, Lisa A.] Univ Texas Sch Publ Hlth, Div Environm & Occupat Hlth Sci, Houston, TX USA. RP Mirabelli, MC (reprint author), Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. EM mmirabel@wakehealth.edu OI Mirabelli, Maria/0000-0002-3540-0085; London, Stephanie/0000-0003-4911-5290 FU National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; Division of Intramural Research, National Institute of Environmental Health Sciences FX The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). Dr. London is supported by the Division of Intramural Research, National Institute of Environmental Health Sciences. NR 41 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD FEB PY 2012 VL 54 IS 2 BP 157 EP 165 DI 10.1097/JOM.0b013e31823e3a52 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 891DP UT WOS:000300197000006 PM 22157701 ER PT J AU Raghwani, J Thomas, XV Koekkoek, SM Schinkel, J Molenkamp, R van de Laar, TJ Takebe, Y Tanaka, Y Mizokami, M Rambaut, A Pybus, OG AF Raghwani, Jayna Thomas, Xiomara V. Koekkoek, Sylvie M. Schinkel, Janke Molenkamp, Richard van de Laar, Thijs J. Takebe, Yutaka Tanaka, Yasuhito Mizokami, Masashi Rambaut, Andrew Pybus, Oliver G. TI Origin and Evolution of the Unique Hepatitis C Virus Circulating Recombinant Form 2k/1b SO JOURNAL OF VIROLOGY LA English DT Article ID INTRAVENOUS-DRUG-USERS; MOLECULAR EPIDEMIOLOGY; POPULATION-DYNAMICS; HCV GENOTYPES; ST-PETERSBURG; INFECTION; SEQUENCES; IDENTIFICATION; INFERENCE; MODELS AB Since its initial identification in St. Petersburg, Russia, the recombinant hepatitis C virus (HCV) 2k/1b has been isolated from several countries throughout Eurasia. The 2k/1b strain is the only recombinant HCV to have spread widely, raising questions about the epidemiological background in which it first appeared. In order to further understand the circumstances by which HCV recombinants might be formed and spread, we estimated the date of the recombination event that generated the 2k/1b strain using a Bayesian phylogenetic approach. Our study incorporates newly isolated 2k/1b strains from Amsterdam, The Netherlands, and has employed a hierarchical Bayesian framework to combine information from different genomic regions. We estimate that 2k/1b originated sometime between 1923 and 1956, substantially before the first detection of the strain in 1999. The timescale and the geographic spread of 2k/1b suggest that it originated in the former Soviet Union at about the time that the world's first centralized national blood transfusion and storage service was being established. We also reconstructed the epidemic history of 2k/1b using coalescent theory-based methods, matching patterns previously reported for other epidemic HCV subtypes. This study demonstrates the practicality of jointly estimating dates of recombination from flanking regions of the breakpoint and further illustrates that rare genetic-exchange events can be particularly informative about the underlying epidemiological processes. C1 [Raghwani, Jayna; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh, Midlothian, Scotland. [Thomas, Xiomara V.; Koekkoek, Sylvie M.; Schinkel, Janke; Molenkamp, Richard] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, Sect Clin Virol, NL-1105 AZ Amsterdam, Netherlands. [van de Laar, Thijs J.] Vrije Univ Amsterdam, Med Ctr, Dept Med Microbiol & Infect Control, Amsterdam, Netherlands. [Takebe, Yutaka] Natl Inst Infect Dis, AIDS Res Ctr, Tokyo, Japan. [Tanaka, Yasuhito] Nagoya City Univ, Grad Sch Med Sci, Liver Unit, Nagoya, Aichi, Japan. [Tanaka, Yasuhito] Nagoya City Univ, Grad Sch Med Sci, Dept Virol, Nagoya, Aichi, Japan. [Mizokami, Masashi] Natl Ctr Global Hlth & Med, Res Ctr Hepatitis & Immunol, Ichikawa, Japan. [Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. RP Raghwani, J (reprint author), Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh, Midlothian, Scotland. EM jna.raghwani@gmail.com; oliver.pybus@zoo.ox.ac.uk RI pybus, oliver/B-2640-2012; Schinkel, Janke/I-3099-2012; OI Schinkel, Janke/0000-0002-1112-0644; Pybus, Oliver/0000-0002-8797-2667; Raghwani, Jayna/0000-0001-8538-4995; Rambaut, Andrew/0000-0003-4337-3707 FU Wellcome Trust [095831] NR 72 TC 19 Z9 22 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2012 VL 86 IS 4 BP 2212 EP 2220 DI 10.1128/JVI.06184-11 PG 9 WC Virology SC Virology GA 886OA UT WOS:000299862500029 PM 22114341 ER PT J AU Qureshi, H Ma, ZM Huang, Y Hodge, G Thomas, MA DiPasquale, J DeSilva, V Fritts, L Bett, AJ Casimiro, DR Shiver, JW Robert-Guroff, M Robertson, MN McChesney, MB Gilbert, PB Miller, CJ AF Qureshi, Huma Ma, Zhong-Min Huang, Ying Hodge, Gregory Thomas, Michael A. DiPasquale, Janet DeSilva, Veronique Fritts, Linda Bett, Andrew J. Casimiro, Danilo R. Shiver, John W. Robert-Guroff, Marjorie Robertson, Michael N. McChesney, Michael B. Gilbert, Peter B. Miller, Christopher J. TI Low-Dose Penile SIVmac251 Exposure of Rhesus Macaques Infected with Adenovirus Type 5 (Ad5) and Then Immunized with a Replication-Defective Ad5-Based SIV gag/pol/nef Vaccine Recapitulates the Results of the Phase IIb Step Trial of a Similar HIV-1 Vaccine SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; MAMU-B-ASTERISK-08-POSITIVE MACAQUES; CHALLENGE EXPERIMENTS; VIRAL REPLICATION; MEDIATED-IMMUNITY; VAGINAL CHALLENGE; MONKEYS; RESPONSES; EFFICACY AB The Step Trial showed that the MRKAd5 HIV-1 subtype B Gag/Pol/Nef vaccine did not protect men from HIV infection or reduce setpoint plasma viral RNA (vRNA) levels but, unexpectedly, it did modestly enhance susceptibility to HIV infection in adenovirus types (Ad5)-seropositive, uncircumcised men. As part of the process to understand the results of the Step Trial, we designed a study to determine whether rhesus macaques chronically infected with a host-range mutant Ad5 (Ad5hr) and then immunized with a replication defective Ad5 SIVmac239 Gag/Pol/Nef vaccine were more resistant or susceptible to SIV infection than unimmunized rhesus macaques challenged with a series of escalating dose penile exposures to SIVmac 251. The Ad5 SLY vaccine induced CD8(+) T cell responses in 70% of the monkeys, which is similar to the proportion of humans that responded to the vaccine in the Step Trial. However, the vaccine did not protect vaccinated animals from penile SIV challenge. At the lowest SIV exposure dose (10(3) 50% tissue culture infective doses), 2 of 9 Ad5-seropositive animals immunized with the Ad5 SIV vaccine became infected compared to 0 of 34 animals infected in the other animal groups (naive animals, Ad5-seropositive animals immunized with the empty Ad5 vector, Ad5-seronegative animals immunized with the Ad5 SIV vaccine, and Ad5-seronegative animals immunized with the empty Ad5 vector). Penile exposure to more concentrated virus inocula produced similar rates of infection in all animal groups. Although setpoint viral loads were unaffected in Step vaccinees, the Ad5 SLY-immunized animals had significantly lower acute-phase plasma vRNA levels compared to unimmunized animals. Thus, the results of the nonhuman primate (NHP) study described here recapitulate the lack of protection against HIV acquisition seen in the Step Trial and suggest a greater risk of infection in the Ad5-seropositive animals immunized with the Ad5 SLY vaccine. Further studies are necessary to confirm the enhancement of virus acquisition and to discern associated mechanisms. C1 [Qureshi, Huma; Ma, Zhong-Min; DeSilva, Veronique; Fritts, Linda; Miller, Christopher J.] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. [Qureshi, Huma; Ma, Zhong-Min; Hodge, Gregory; DeSilva, Veronique; Fritts, Linda; McChesney, Michael B.; Miller, Christopher J.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Huang, Ying; Gilbert, Peter B.] Fred Hutchinson Canc Res Ctr, SCHARP, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. [Thomas, Michael A.; DiPasquale, Janet; Robert-Guroff, Marjorie] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Bett, Andrew J.; Casimiro, Danilo R.; Shiver, John W.; Robertson, Michael N.] Merck Res Labs, West Point, PA USA. RP Miller, CJ (reprint author), Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. EM cjmiller@ucdavis.edu FU Public Health Service from the National Center for Research Resources [P51RR00169]; National Institute of Allergy and Infectious Diseases [P01 AI8227, R37 AI054165]; NIH, National Cancer Institute FX This study was supported by Public Health Service grants P51RR00169 from the National Center for Research Resources, P01 AI8227 (to C.J.M.) and R37 AI054165 (to P.B.G.) from the National Institute of Allergy and Infectious Diseases and in part by the Intramural Research Program of the NIH, National Cancer Institute. NR 47 TC 52 Z9 54 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2012 VL 86 IS 4 BP 2239 EP 2250 DI 10.1128/JVI.06175-11 PG 12 WC Virology SC Virology GA 886OA UT WOS:000299862500032 PM 22156519 ER PT J AU Jewell, CM Scoltock, AB Hamel, BL Yudt, MR Cidlowski, JA AF Jewell, Christine M. Scoltock, Alyson B. Hamel, Brant L. Yudt, Matthew R. Cidlowski, John A. TI Complex Human Glucocorticoid Receptor dim Mutations Define Glucocorticoid Induced Apoptotic Resistance in Bone Cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID DNA-BINDING DOMAIN; NF-KAPPA-B; GENE-EXPRESSION; NUCLEAR RECEPTORS; TARGET GENES; MECHANISMS; TRANSCRIPTION; REPRESSION; PROTEIN; ANTAGONISM AB A mutation in the D-loop of the second zinc finger of the DNA-binding domain of the human glucocorticoid receptor (hGR), A458T (GR(dim)), has been suggested to be essential for dimerization and DNA binding of the GR, and genetically altered GR(dim) mice survive, whereas murine GR knockout mice die. Interestingly, thymocytes isolated from the GR(dim) mice were reported to be resistant to glucocorticoid-induced apoptosis. To further evaluate the dim mutations in glucocorticoid-induced apoptosis, we stably expressed either the hGR(dim) (A458T) or the hGR(dim4) (A458T, R460D, D462C, and N454D) mutant receptors in human osteosarcoma (U-2 OS) cells that are devoid of hGR and unresponsive to glucocorticoids. We analyzed these cell lines by comparison with a stable expression hGR alpha U-2 OS cell line, which undergoes apoptosis after glucocorticoid treatment. Transient reporter gene assays with glucocorticoid response element-driven vectors revealed that the hGR(dim) mutation had diminished steroid responsiveness and cells carrying the hGR(dim4) mutation were unresponsive to steroid, whereas glucocorticoid-induced nuclear factor kappa B repression was unaffected by either mutation. Interestingly, both the hGR(dim) and hGR(dim4) receptors readily formed dimers as measured by immunoprecipitation. Examination of GR-mediated apoptosis showed that hGR(dim) cells were only partially resistant to apoptosis, whereas hGR(dim4) cells were completely resistant to glucocorticoid-induced cell death despite remaining sensitive to other apoptotic stimuli. Global gene expression analysis revealed that hGR(dim4) cells widely regulated gene expression but differentially regulated apoptotic mRNA when compared with cells expressing wild-type hGR alpha. These studies challenge conclusions drawn from previous studies of GR dim mutants. (Molecular Endocrinology 26: 244-256, 2012) C1 [Jewell, Christine M.; Scoltock, Alyson B.; Hamel, Brant L.; Yudt, Matthew R.; Cidlowski, John A.] NIEHS, NIH, Lab Signal Transduct, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Jewell, CM (reprint author), NIEHS, NIH, Lab Signal Transduct, Dept Hlth & Human Serv, 111 TW Alexander Dr,Bldg 101,MD F3-07, Res Triangle Pk, NC 27709 USA. EM jewell@niehs.nih.gov FU National Institutes of Health, National Institute of Environmental Health Sciences FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 44 TC 25 Z9 25 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 2012 VL 26 IS 2 BP 244 EP 256 DI 10.1210/me.2011-1116 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 888LJ UT WOS:000300004700004 PM 22174376 ER PT J AU Anderson, KA Lin, FM Ribar, TJ Stevens, RD Muehlbauer, MJ Newgard, CB Means, AR AF Anderson, Kristin A. Lin, Fumin Ribar, Thomas J. Stevens, Robert D. Muehlbauer, Michael J. Newgard, Christopher B. Means, Anthony R. TI Deletion of CaMKK2 from the Liver Lowers Blood Glucose and Improves Whole-Body Glucose Tolerance in the Mouse SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; INSULIN-RESISTANCE; HEPATIC GLUCONEOGENESIS; HISTONE DEACETYLASES; MUSCLE; TRANSCRIPTION; HOMEOSTASIS; BETA; PHOSPHORYLATION AB Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a member of the Ca2+/CaM-dependent protein kinase family that is expressed abundantly in brain. Previous work has revealed that CaMKK2 knockout (CaMKK2 KO) mice eat less due to a central nervous system -signaling defect and are protected from diet-induced obesity, glucose intolerance, and insulin resistance. However, here we show that pair feeding of wild-type mice to match food consumption of CAMKK2 mice slows weight gain but fails to protect from diet-induced glucose intolerance, suggesting that other alterations in CaMKK2 KO mice are responsible for their improved glucose metabolism. CaMKK2 is shown to be expressed in liver and acute, specific reduction of the kinase in the liver of high-fat diet-fed CaMKK2(floxed) mice results in lowered blood glucose and improved glucose tolerance. Primary hepatocytes isolated from CaMKK2 KO mice produce less glucose and have decreased mRNA encoding peroxisome proliferator-activated receptor gamma coactivator 1-alpha and the gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, and these mRNA fail to respond specifically to the stimulatory effect of catecholamine in a cell-autonomous manner. The mechanism responsible for suppressed gene induction in CaMKK2 KO hepatocytes may involve diminished phosphorylation of histone deacetylase 5, an event necessary in some contexts for derepression of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha promoter. Hepatocytes from CaMKK2 KO mice also show increased rates of de novo lipogenesis and fat oxidation. The changes in fat metabolism observed correlate with steatotic liver and altered acyl carnitine metabolomic profiles in CaMKK2 KO mice. Collectively, these results are consistent with suppressed catecholamine-induced induction of gluconeogenic gene expression in CaMKK2 KO mice that leads to improved whole-body glucose homeostasis despite the presence of increased hepatic fat content. (Molecular Endocrinology 26: 281-291, 2012) C1 [Anderson, Kristin A.] Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA. [Stevens, Robert D.; Muehlbauer, Michael J.] Duke Univ, Sch Med, Dept Med Endocrinol & Metab, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA. [Lin, Fumin] NIEHS, Res Triangle Pk, NC USA. RP Anderson, KA (reprint author), Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA. RI LIN, Fumin/D-5709-2015 OI LIN, Fumin/0000-0003-1229-0685 FU NIH [GM033976, P01DK58398] FX This work was supported by NIH Grants to A. R. M. (GM033976) and to C.B.N. (P01DK58398). NR 46 TC 10 Z9 10 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 2012 VL 26 IS 2 BP 281 EP 291 DI 10.1210/me.2011-1299 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 888LJ UT WOS:000300004700007 PM 22240810 ER PT J AU Bear, AS Morgan, RA Cornetta, K June, CH Binder-Scholl, G Dudley, ME Feldman, SA Rosenberg, SA Shurtleff, SA Rooney, CM Heslop, HE Dotti, G AF Bear, Adham S. Morgan, Richard A. Cornetta, Kenneth June, Carl H. Binder-Scholl, Gwendolyn Dudley, Mark E. Feldman, Steven A. Rosenberg, Steven A. Shurtleff, Sheila A. Rooney, Cliona M. Heslop, Helen E. Dotti, Gianpietro TI Replication-Competent Retroviruses in Gene-Modified T Cells Used in Clinical Trials: Is It Time to Revise the Testing Requirements? SO MOLECULAR THERAPY LA English DT Editorial Material ID APE LEUKEMIA-VIRUS; PACKAGING CELLS; LYMPHOCYTES; VECTORS; THERAPY; RECEPTORS C1 [Bear, Adham S.; Rooney, Cliona M.; Heslop, Helen E.; Dotti, Gianpietro] Methodist Hosp, Houston, TX 77030 USA. [Morgan, Richard A.; Dudley, Mark E.; Feldman, Steven A.; Rosenberg, Steven A.] NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Cornetta, Kenneth] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA. [June, Carl H.; Binder-Scholl, Gwendolyn] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Shurtleff, Sheila A.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. [Rooney, Cliona M.; Heslop, Helen E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Rooney, Cliona M.; Dotti, Gianpietro] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. [Heslop, Helen E.; Dotti, Gianpietro] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Bear, Adham S.; Rooney, Cliona M.; Heslop, Helen E.; Dotti, Gianpietro] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. RP Dotti, G (reprint author), Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, 6621 Fannin St,MC 3-3320, Houston, TX 77030 USA. EM gdotti@bcm.edu FU NCI NIH HHS [P01 CA094237, 3P50CA126752, P01 CA094237-10, P01CA094237, P50 CA126752, P50 CA126752-05]; NCRR NIH HHS [P40 RR024928, P40 RR024928-03]; NHLBI NIH HHS [5U54HL081007, P40 HL116242, T32 HL092332, U54 HL081007, U54 HL081007-05] NR 15 TC 18 Z9 18 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD FEB PY 2012 VL 20 IS 2 BP 246 EP 249 DI 10.1038/mt.2011.288 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 888CM UT WOS:000299981400002 PM 22297819 ER PT J AU Prescott, J Wentzensen, IM Savage, SA De Vivo, I AF Prescott, Jennifer Wentzensen, Ingrid M. Savage, Sharon A. De Vivo, Immaculata TI Epidemiologic evidence for a role of telomere dysfunction in cancer etiology SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE Telomere length; Cancer; Epidemiology ID INCIDENT COLORECTAL-CARCINOMA; BREAST-CANCER; CELLULAR SENESCENCE; CIGARETTE-SMOKING; BLOOD-CELLS; PREDISPOSITION FACTOR; OXIDATIVE STRESS; QUANTITATIVE PCR; BLADDER-CANCER; CHROMOSOME 17P AB Telomeres, the dynamic nucleoprotein structures at the ends of linear chromosomes, maintain the genomic integrity of a cell. Telomere length shortens with age due to the incomplete replication of DNA ends with each cell division as well as damage incurred by oxidative stress. Patterns of telomere shortening, genomic instability, and telomerase expression in many cancer tissues compared to adjacent normal tissue implicate telomere crisis as a common crucial event in malignant transformation. In order to understand the role of telomere length in cancer etiology, most epidemiologic studies have measured average telomere length of peripheral blood or buccal cell DNA as a surrogate tissue biomarker of telomere dysfunction and cancer risk. In this review, we present the results from epidemiologic investigations conducted of telomere length and cancer risk. We note differences in reported associations based on study design, which may be due to biases intrinsic to retrospective studies. Finally, we conclude with study design considerations as future investigations are needed to elucidate the relationship between telomere length and a number of cancer sites. (C) 2011 Elsevier B.V. All rights reserved. C1 [Prescott, Jennifer; De Vivo, Immaculata] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [Prescott, Jennifer; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Prescott, Jennifer; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Wentzensen, Ingrid M.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP De Vivo, I (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM nhjxp@channing.harvard.edu; wentzeni@mail.nih.gov; savagesh@mail.nih.gov; devivo@channing.harvard.edu RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU National Institute of Health [CA65725, CA134958, CA082838]; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health FX JP and IDV are supported by the National Institute of Health (grants: CA65725, CA134958, CA082838). This work was supported, in part, by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. NR 76 TC 39 Z9 39 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD FEB 1 PY 2012 VL 730 IS 1-2 SI SI BP 75 EP 84 DI 10.1016/j.mrfmmm.2011.06.009 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 889MW UT WOS:000300078800011 PM 21756922 ER PT J AU Blank, M Tang, Y Yamashita, M Burkett, SS Cheng, SY Zhang, YE AF Blank, Michael Tang, Yi Yamashita, Motozo Burkett, Sandra S. Cheng, Steven Y. Zhang, Ying E. TI A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20 SO NATURE MEDICINE LA English DT Article ID UBIQUITIN LIGASE SMURF2; BREAST-CANCER CELLS; HISTONE H2B; DEPENDENT DEGRADATION; H3 METHYLATION; UBIQUITYLATION; DNA; MONOUBIQUITINATION; ELONGATION; EXPRESSION AB In addition to allelic mutations, cancers are known to harbor alterations in their chromatin landscape. Here we show that genomic ablation of Smad ubiquitin regulatory factor 2 (Smurf2), a HECT-domain E3 ubiquitin ligase, results in dysregulation of both the DNA damage response and genomic stability, culminating in increased susceptibility to various types of cancers in aged mice. We show that Smurf2 regulates the monoubiquitination of histone H2B as well as the trimethylation of histone H3 at Lys4 and Lys79 by targeting ring finger protein 20 (RNF20) for proteasomal degradation in both mouse and human cells. We also show that Smurf2 and RNF20 are colocalized at the gamma-H2AX foci of double-stranded DNA breaks in the nucleus. Thus, Smurf2 has a tumor suppression function that normally maintains genomic stability by controlling the epigenetic landscape of histone modifications through RNF20. C1 [Blank, Michael; Tang, Yi; Yamashita, Motozo; Zhang, Ying E.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Burkett, Sandra S.] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. [Cheng, Steven Y.] Nanjing Med Univ, Dept Dev Genet, Sch Basic Med Sci, Nanjing, Jiangsu, Peoples R China. RP Zhang, YE (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA. EM zhangyin@mail.nih.gov RI Zhang, Ying/G-3657-2015 OI Zhang, Ying/0000-0003-2753-7601 FU US National Cancer Institute, US National Institutes of Health, Center for Cancer Research; Japan Society for the Promotion of Science [21689053] FX We thank M. Anver for pathology services, V. Barr for assistance with microscope, X. Wu for assistance with the microarray experiments, N. Morris for the animal husbandry and N. Teja for assistance with cell culture. We also thank K. Sixt for comments on the manuscript. This research is supported by the Intramural Research Program of the US National Cancer Institute, US National Institutes of Health, Center for Cancer Research. M.Y. was partially supported by the Japan Society for the Promotion of Science grant 21689053. NR 38 TC 53 Z9 55 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD FEB PY 2012 VL 18 IS 2 BP 227 EP 234 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 890JG UT WOS:000300140300036 PM 22231558 ER PT J AU Chen, F Liu, ZG Wu, WH Rozo, C Bowdridge, S Millman, A Van Rooijen, N Urban, JF Wynn, TA Gause, WC AF Chen, Fei Liu, Zhugong Wu, Wenhui Rozo, Cristina Bowdridge, Scott Millman, Ariel Van Rooijen, Nico Urban, Joseph F., Jr. Wynn, Thomas A. Gause, William C. TI An essential role for T(H)2-type responses in limiting acute tissue damage during experimental helminth infection SO NATURE MEDICINE LA English DT Article ID ALTERNATIVELY ACTIVATED MACROPHAGES; INDUCED PULMONARY INFLAMMATION; INDUCED LUNG INJURY; NEMATODE PARASITES; T-CELLS; ACUTE SCHISTOSOMIASIS; ALVEOLAR MACROPHAGES; IMMUNE-RESPONSES; GENE-EXPRESSION; TYPE-2 IMMUNITY AB Helminths induce potent T helper 2 (T(H)2)-type immune responses that can mediate worm expulsion, but the role of this response in controlling the acute tissue damage caused by migrating multicellular parasites through vital tissues remains uncertain. We used a helminth infection model in which parasitic nematode larvae migrate transiently through the lung, resulting in hemorrhage and inflammation. We found that IL-17 initially contributed to inflammation and lung damage, whereas subsequent IL-4 receptor (IL-4R) signaling reduced elevations in IL-17 mRNA levels, enhanced the expression of insulin-like growth factor 1 (IGF-1) and IL-10 and stimulated the development of M2 macrophages, all of which contributed to the rapid resolution of tissue damage. These studies indicate an essential role for T(H)2-type immune responses in mediating acute wound healing during helminth infection. C1 [Chen, Fei; Liu, Zhugong; Wu, Wenhui; Rozo, Cristina; Bowdridge, Scott; Millman, Ariel; Gause, William C.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. [Chen, Fei; Liu, Zhugong; Wu, Wenhui; Rozo, Cristina; Bowdridge, Scott; Millman, Ariel; Gause, William C.] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Immun & Inflammat, Newark, NJ 07103 USA. [Van Rooijen, Nico] Vrije Univ Amsterdam, Med Ctr, Dept Mol Cell Biol, Amsterdam, Netherlands. [Urban, Joseph F., Jr.] ARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD USA. [Wynn, Thomas A.] NIAID, Parasit Dis Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Gause, WC (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. EM gausewc@umdnj.edu RI Wynn, Thomas/C-2797-2011; OI Urban, Joseph/0000-0002-1590-8869 FU US National Institutes of Health [AI031678] FX This work was supported by US National Institutes of Health grants AI031678. NR 56 TC 150 Z9 152 U1 4 U2 28 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 260 EP 266 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 890JG UT WOS:000300140300040 PM 22245779 ER PT J AU Cox, S Rosten, E Monypenny, J Jovanovic-Talisman, T Burnette, DT Lippincott-Schwartz, J Jones, GE Heintzmann, R AF Cox, Susan Rosten, Edward Monypenny, James Jovanovic-Talisman, Tijana Burnette, Dylan T. Lippincott-Schwartz, Jennifer Jones, Gareth E. Heintzmann, Rainer TI Bayesian localization microscopy reveals nanoscale podosome dynamics SO NATURE METHODS LA English DT Article ID HIDDEN MARKOV-MODELS; FLUORESCENCE MICROSCOPY; LIVE CELLS; SUPERRESOLUTION; STORM; LIMIT AB We describe a localization microscopy analysis method that is able to extract results in live cells using standard fluorescent proteins and xenon arc lamp illumination. Our Bayesian analysis of the blinking and bleaching (38 analysis) method models the entire dataset simultaneously as being generated by a number of fluorophores that may or may not be emitting light at any given time. The resulting technique allows many overlapping fluorophores in each frame and unifies the analysis of the Localization from blinking and bleaching events. By modeling the entire dataset, we were able to use each reappearance of a fluorophore to improve the localization accuracy. The high performance of this technique allowed us to reveal the nanoscale dynamics of podosome formation and dissociation throughout an entire cell with a resolution of 50 nm on a 4-s timescale. C1 [Cox, Susan; Monypenny, James; Jones, Gareth E.; Heintzmann, Rainer] Kings Coll London, Randall Div, London WC2R 2LS, England. [Rosten, Edward] Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England. [Rosten, Edward] Comp Vis Consulting Ltd, Woking, Surrey, England. [Jovanovic-Talisman, Tijana; Burnette, Dylan T.; Lippincott-Schwartz, Jennifer] NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. [Heintzmann, Rainer] Univ Jena, Inst Phys Chem, D-6900 Jena, Germany. [Heintzmann, Rainer] Inst Photon Technol, Jena, Germany. RP Cox, S (reprint author), Kings Coll London, Randall Div, Guys Campus, London WC2R 2LS, England. EM susan.cox@kcl.ac.uk RI Heintzmann, Rainer/I-5667-2012; Jones, Gareth/H-2282-2012; OI Jones, Gareth/0000-0001-5879-3048; Jovanovic-Talisman, Tijana/0000-0003-1928-4763 FU EU [GA 215597, ITN 237946 T3Ne]; Wellcome Trust; Medical Research Council (UK); Royal Society FX We acknowledge helpful discussions with A. Fraser, F. Viola, P. Fox-Roberts, O. Mandula and J. Sleep. We thank M. Kielhorn for assistance in aligning the optical system and K. Glocer for critical reading of the manuscript. We thank M. Parsons (King's College London) for providing the template pLasmid. We acknowledge support from the EU Seventh Framework Programme (FP7 Project GA 215597 (S.C. and R.H.), EU. FP7 Project ITN 237946 T3Net (G.E.J.)), the Wellcome Trust (S.C., J.M. and G.E.J.), the Medical Research Council (UK) (G.E.J.) and the Royal Society (S.C.). NR 25 TC 135 Z9 140 U1 4 U2 52 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD FEB PY 2012 VL 9 IS 2 BP 195 EP 200 DI 10.1038/NMETH.1812 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 888UH UT WOS:000300029600033 ER PT J AU Sheng, ZH Cai, Q AF Sheng, Zu-Hang Cai, Qian TI Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; DYNAMIN-RELATED PROTEIN-1; FAST AXONAL-TRANSPORT; AUTOPHAGY-LYSOSOMAL FUNCTION; KINESIN HEAVY-CHAIN; NERVE GROWTH-FACTOR; CYTOPLASMIC DYNEIN; IN-VIVO; HIPPOCAMPAL-NEURONS; LIGHT-CHAIN AB Mitochondria have a number of essential roles in neuronal function. Their complex mobility patterns within neurons are characterized by frequent changes in direction. Mobile mitochondria can become stationary or pause in regions that have a high metabolic demand and can move again rapidly in response to physiological changes. Defects in mitochondrial transport are implicated in the pathogenesis of several major neurological disorders. Research into the mechanisms that regulate mitochondrial transport is thus an important emerging frontier. C1 [Sheng, Zu-Hang; Cai, Qian] NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. [Cai, Qian] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA. RP Sheng, ZH (reprint author), NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Room 28-215,35 Convent Dr, Bethesda, MD 20892 USA. EM shengz@ninds.nih.gov FU US National Institute of Neurological Disorder and Stroke (NINDS); US National Institutes of Health (NIH); NIH [K99] FX The authors thank M. Davis for editing and other members of the Sheng laboratory for their assistance and discussion. This work was supported by the Intramural Research Program of the US National Institute of Neurological Disorder and Stroke (NINDS), US National Institutes of Health (NIH) (Z.-H.S.) and the NIH Pathway to Independence Award K99 (Q.C.). NR 179 TC 201 Z9 208 U1 9 U2 59 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD FEB PY 2012 VL 13 IS 2 BP 77 EP 93 DI 10.1038/nrn3156 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 888AN UT WOS:000299976300007 PM 22218207 ER PT J AU Kales, SC Ryan, PE Lipkowitz, S AF Kales, Stephen C. Ryan, Philip E. Lipkowitz, Stanley TI Cbl exposes its RING finger SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID INDUCED CONFORMATIONAL-CHANGE; UBIQUITIN-CONJUGATING ENZYME; GROWTH-FACTOR RECEPTOR; T-CELLS; LIGASE ACTIVITY; C-CBL; PROTEIN LIGASE; DOMAIN; KINASE; ACTIVATION AB The Cbl family of RING finger ubiquitin ligases regulates signaling in many systems. Two new studies provide a structural basis for how phosphorylation of a specific tyrosine in the Cbl proteins enhances their ubiquitin ligase activity, giving insight into how ubiquitination by Cbl proteins is restricted to specific substrates. C1 [Kales, Stephen C.; Ryan, Philip E.; Lipkowitz, Stanley] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Kales, SC (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, US Natl Inst Hlth, Bldg 37, Bethesda, MD 20892 USA. EM lipkowis@mail.nih.gov NR 29 TC 11 Z9 11 U1 0 U2 1 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 131 EP 133 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 888UF UT WOS:000300029400002 PM 22301873 ER PT J AU Martiniova, L Cleary, S Lai, EW Kiesewetter, DO Seidel, J Dawson, LF Phillips, JK Thomasson, D Chen, XY Eisenhofer, G Powers, JF Kvetnansky, R Pacak, K AF Martiniova, Lucia Cleary, Susannah Lai, Edwin W. Kiesewetter, Dale O. Seidel, Jurgen Dawson, Linda F. Phillips, Jacqueline K. Thomasson, David Chen, Xiaoyuan Eisenhofer, Graeme Powers, James F. Kvetnansky, Richard Pacak, Karel TI Usefulness of [F-18]-DA and [F-18]-DOPA for PET imaging in a mouse model of pheochromocytoma SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE Pheochromocytoma; PET; MicroCT; MRI; Metastatic mice model; Fluorodopamine; Fluorodopa; Norepinephrine transporter; Vesicular monoamine transporter ID POSITRON-EMISSION-TOMOGRAPHY; VESICULAR MONOAMINE TRANSPORTER; METASTATIC PHEOCHROMOCYTOMA; NORADRENALINE TRANSPORTER; CONTRAST ENHANCEMENT; ENDOCRINE-CELLS; EXPRESSION; LOCALIZATION; TUMORS; PLASMA AB Purpose: To evaluate the usefulness of [F-18]-6-fluorodopamine ([F-18]-DA) and [F-18]-L-6-fluoro-3,4-dihydroxyphenylalanine ([F-18-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters I and 2 (VMAT1 and VMAT2), all important for [F-18]-DA and [F-18]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse. Methods: SUVmax values were calculated from [F-18]-DA and [F-18]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated. Results: [F-18]-DA detected less metastatic lesions compared to [F-18]-DOPA. TLR values for liver metastases were 2.26-2.71 for [F-18]-DOPA and 1.83-2.83 for [F-18]-DA. A limited uptake of [F-18]-DA was found in s.c. tumors (TLR=0.22-0.27) compared to [F-18]-DOPA (TLR=1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [F-18]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [F-18]-DOPA was found to utilize only VMAT2. Conclusion: MRI was superior in the detection of all organ tumors compared to microCT and PET. [F-18]-DOPA had overall better sensitivity than [F-18]-DA for the detection of metastases. Subcutaneous tumors were localized only with [F-18]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [F-18]-DOPA provides better visualization of lesions than [F-18]-DA. (C) 2012 Elsevier Inc. All rights reserved. C1 [Martiniova, Lucia; Lai, Edwin W.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Cleary, Susannah] Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. [Kiesewetter, Dale O.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Seidel, Jurgen] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Dawson, Linda F.; Phillips, Jacqueline K.] Murdoch Univ, Fac Hlth Sci, Perth, WA 6150, Australia. [Phillips, Jacqueline K.] Macquarie Univ, Australian Sch Adv Med, Sydney, NSW 2109, Australia. [Thomasson, David] NIH, Lab Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Eisenhofer, Graeme] Univ Dresden, Dept Med, D-01307 Dresden, Germany. [Eisenhofer, Graeme] Univ Dresden, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany. [Powers, James F.] Tufts Med Ctr, Dept Pathol, Boston, MA 02111 USA. [Martiniova, Lucia; Kvetnansky, Richard] Slovak Acad Sci, Inst Expt Endocrinol, SK-83306 Bratislava, Slovakia. RP Pacak, K (reprint author), NICHD, NIH, 10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov OI Phillips, Jacqueline/0000-0002-4917-7734 FU Eunice Kennedy Shriver National Institutes of Child Health and Human Development; Warren Grant Magnuson Clinical Center; National Institute of Neurological Disorders and Stroke; National Institute of Biomedical Imaging and Bioengineering, National Cancer Institute; PheoPara Alliance; [APVV-0148-06] FX We would like to acknowledge the valuable assistance of the colleagues in our group; we thank Mr. Stephen Uyeno and Mr. Eli Thompson for their assistance with animals. This research was supported (in part) by the Intramural Research Program of the Eunice Kennedy Shriver National Institutes of Child Health and Human Development, Warren Grant Magnuson Clinical Center, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, National Cancer Institute, by the grant from the PheoPara Alliance (to J.P.) and APVV-0148-06 (to R.K.). The authors have no conflict of interest to disclose. NR 44 TC 7 Z9 7 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD FEB PY 2012 VL 39 IS 2 BP 215 EP 226 DI 10.1016/j.nucmedbio.2011.07.007 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 890BY UT WOS:000300121300006 PM 21958851 ER PT J AU Machado-Vieira, R Ibrahim, L Henter, LD Zarate, CA AF Machado-Vieira, Rodrigo Ibrahim, Lobna Henter, Loline D. Zarate, Carlos A., Jr. TI Novel glutamatergic agents for major depressive disorder and bipolar disorder SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Review DE Bipolar disorder; Depression; Glutamate; Mood disorders; Novel treatments; Pathophysiology ID MAGNETIC-RESONANCE-SPECTROSCOPY; D-ASPARTATE ANTAGONIST; OPEN-LABEL TRIAL; STAR-ASTERISK-D; SEROTONIN REUPTAKE INHIBITORS; OBSESSIVE-COMPULSIVE DISORDER; RAPID ANTIDEPRESSANT RESPONSE; ANTERIOR CINGULATE ACTIVITY; MGLU5 RECEPTOR ANTAGONIST; GAMMA-AMINOBUTYRIC-ACID AB Mood disorders such as major depressive disorder (MDD) and bipolar disorder (BPD) are common, chronic, recurrent mental illnesses that affect the lives and functioning of millions of individuals worldwide. Growing evidence suggests that the glutamatergic system is central to the neurobiology and treatment of these disorders. Here, we review data supporting the involvement of the glutamatergic system in the pathophysiology of mood disorders as well as the efficacy of glutamatergic agents as novel therapeutics. Published by Elsevier Inc. C1 [Ibrahim, Lobna; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Sch Med, L1M 27, Inst & Dept Psychiat,USP, Sao Paulo, Brazil. [Henter, Loline D.] NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), 10 Ctr Dr,CRC,7 Southeast Unit,Rm 7-3465, Bethesda, MD 20892 USA. EM zaratec@intra.nimh.nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU National Institute of Mental Heath, National Institutes of Health (NIMH-NIH) FX The authors gratefully acknowledge the support of the Intramural Research Program of the National Institute of Mental Heath, National Institutes of Health (IRP-NIMH-NIH). Dr. Zarate is listed among the inventors on a patent application submitted for the use of ketamine in depression. He has assigned his rights on the patent to the US government. The authors have no conflict of interest to disclose, financial or otherwise. NR 178 TC 39 Z9 40 U1 3 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 2012 VL 100 IS 4 SI SI BP 678 EP 687 DI 10.1016/j.pbb.2011.09.010 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 888UE UT WOS:000300029300004 PM 21971560 ER PT J AU Bentolila, S Stefanov, S AF Bentolila, Stephane Stefanov, Stefan TI A Reevaluation of Rice Mitochondrial Evolution Based on the Complete Sequence of Male-Fertile and Male-Sterile Mitochondrial Genomes SO PLANT PHYSIOLOGY LA English DT Article ID CYTOPLASMIC MALE-STERILITY; ARABIDOPSIS-THALIANA; DNA-MOLECULES; MAIZE; GENE; PLANTS; RECOMBINATION; RESTORER; MUTANT; ORYZA AB Plant mitochondrial genomes have features that distinguish them radically from their animal counterparts: a high rate of rearrangement, of uptake and loss of DNA sequences, and an extremely low point mutation rate. Perhaps the most unique structural feature of plant mitochondrial DNAs is the presence of large repeated sequences involved in intramolecular and intermolecular recombination. In addition, rare recombination events can occur across shorter repeats, creating rearrangements that result in aberrant phenotypes, including pollen abortion, which is known as cytoplasmic male sterility (CMS). Using next-generation sequencing, we pyrosequenced two rice (Oryza sativa) mitochondrial genomes that belong to the indica subspecies. One genome is normal, while the other carries the wild abortive-CMS. We find that numerous rearrangements in the rice mitochondrial genome occur even between close cytotypes during rice evolution. Unlike maize (Zea mays), a closely related species also belonging to the grass family, integration of plastid sequences did not play a role in the sequence divergence between rice cytotypes. This study also uncovered an excellent candidate for the wild abortive-CMS-encoding gene; like most of the CMS-associated open reading frames that are known in other species, this candidate was created via a rearrangement, is chimeric in structure, possesses predicted transmembrane domains, and coopted the promoter of a genuine mitochondrial gene. Our data give new insights into rice mitochondrial evolution, correcting previous reports. C1 [Bentolila, Stephane] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. [Stefanov, Stefan] Natl Lib Med, Bethesda, MD 20892 USA. RP Bentolila, S (reprint author), Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. EM sb46@cornell.edu RI Bentolila, Stephane/P-2361-2015 OI Bentolila, Stephane/0000-0003-2805-7298 FU U.S. Department of Agriculture National Research Initiative [2006-35301-16889] FX This work was supported by the U.S. Department of Agriculture National Research Initiative (grant no. 2006-35301-16889 to S.B.). NR 54 TC 34 Z9 38 U1 0 U2 16 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD FEB PY 2012 VL 158 IS 2 BP 996 EP 1017 DI 10.1104/pp.111.190231 PG 22 WC Plant Sciences SC Plant Sciences GA 889DS UT WOS:000300054300037 PM 22128137 ER PT J AU Averbeck, BB Bobin, T Evans, S Shergill, SS AF Averbeck, B. B. Bobin, T. Evans, S. Shergill, S. S. TI Emotion recognition and oxytocin in patients with schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Emotion; faces; oxytocin; schizophrenia; social ID MICROTUS-OCHROGASTER; MATERNAL-BEHAVIOR; HUMANS; FACES; VASOPRESSIN; IDENTITY; VALENCE; MEMORY; BRAIN; RATS AB Background. Studies have suggested that patients with schizophrenia are impaired at recognizing emotions. Recently, it has been shown that the neuropeptide oxytocin can have beneficial effects on social behaviors. Method. To examine emotion recognition deficits in patients and see whether oxytocin could improve these deficits, we carried out two experiments. In the first experiment we recruited 30 patients with schizophrenia and 29 age-and IQ-matched control subjects, and gave them an emotion recognition task. Following this, we carried out a second experiment in which we recruited 21 patients with schizophrenia for a double-blind, placebo-controlled cross-over study of the effects of oxytocin on the same emotion recognition task. Results. In the first experiment we found that patients with schizophrenia had a deficit relative to controls in recognizing emotions. In the second experiment we found that administration of oxytocin improved the ability of patients to recognize emotions. The improvement was consistent and occurred for most emotions, and was present whether patients were identifying morphed or non-morphed faces. Conclusions. These data add to a growing literature showing beneficial effects of oxytocin on social-behavioral tasks, as well as clinical symptoms. Received 10 May 2011; Revised 5 July 2011; Accepted 6 July 2011; First published online 11 August 2011 C1 [Averbeck, B. B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Bobin, T.; Shergill, S. S.] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Bobin, T.; Shergill, S. S.] Kings Coll London, Imaging Lab, Dept Psychosis Studies, London WC2R 2LS, England. [Evans, S.] UCL, Sobell Dept Motor Neurosci & Movement Disorders, Inst Neurol, London, England. RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 9, Bethesda, MD 20892 USA. EM averbeckbb@mail.nih.gov FU Medical Research Council (MRC); National Institutes of Health (NIH), National Institute of Mental Health; GlaxoSmith-Kline FX The authors wish to thank all the volunteers who participated in this study. This work was supported by a Medical Research Council (MRC) project grant to S.S.S. and this work was also supported in part by the Intramural Program of the National Institutes of Health (NIH), National Institute of Mental Health.; S.S.S. has received compensation from GlaxoSmith-Kline over the past 3 years. NR 42 TC 33 Z9 35 U1 1 U2 21 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 259 EP 266 DI 10.1017/S0033291711001413 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 886XL UT WOS:000299887700004 PM 21835090 ER PT J AU Young, KD Erickson, K Nugent, AC Fromm, SJ Mallinger, AG Furey, ML Drevets, WC AF Young, K. D. Erickson, K. Nugent, A. C. Fromm, S. J. Mallinger, A. G. Furey, M. L. Drevets, W. C. TI Functional anatomy of autobiographical memory recall deficits in depression SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Anterior insula; autobiographical memory; depression; fMRI; hippocampus ID MAJOR DEPRESSION; BIPOLAR DISORDER; CINGULATE CORTEX; PERSONAL EVENTS; MOOD CHALLENGE; RETRIEVAL; BRAIN; FMRI; NEUROANATOMY; HIPPOCAMPUS AB Background. Major depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories (AMs). Extensive research has examined the functional anatomical correlates of AM in healthy humans, but no studies have examined the neurophysiological underpinnings of AM deficits in MDD. The goal of the present study was to examine the differences in the hemodynamic response between patients with MDD and controls while they engage in AM recall. Method. Participants (12 unmedicated MDD patients; 14 controls) underwent functional magnetic resonance imaging (fMRI) scanning while recalling AMs in response to positive, negative and neutral cue words. The hemodynamic response during memory recall versus performing subtraction problems was compared between MDD patients and controls. Additionally, a parametric linear analysis examined which regions correlated with increasing arousal ratings. Results. Behavioral results showed that relative to controls, the patients with MDD had fewer specific (p = 0.013), positive (p = 0.030), highly arousing (p = 0.036) and recent (p = 0.020) AMs, and more categorical (p < 0.001) AMs. The blood oxygen level-dependent (BOLD) response in the parahippocampus and hippocampus was higher for memory recall versus subtraction in controls and lower in those with MDD. Activity in the anterior insula was lower for specific AM recall versus subtraction, with the magnitude of the decrement greater in MDD patients. Activity in the anterior cingulate cortex was positively correlated with arousal ratings in controls but not in patients with MDD. Conclusions. We replicated previous findings of fewer specific and more categorical AMs in patients with MDD versus controls. We found differential activity in medial temporal and prefrontal lobe structures involved in AM retrieval between MDD patients and controls as they engaged in AM recall. These neurophysiological deficits may underlie AM recall impairments seen in MDD. Received 6 January 2011; Revised 13 June 2011; Accepted 23 June 2011; First published online 29 July 2011 C1 [Young, K. D.; Drevets, W. C.] Laureate Inst Brain Res, Tulsa, OK 74136 USA. [Young, K. D.; Erickson, K.; Nugent, A. C.; Fromm, S. J.; Mallinger, A. G.; Furey, M. L.; Drevets, W. C.] NIMH, NIH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. [Drevets, W. C.] Univ Oklahoma, Coll Med, Dept Psychiat, Tulsa, OK USA. RP Young, KD (reprint author), Laureate Inst Brain Res, 6655 S Yale Ave, Tulsa, OK 74136 USA. EM kyoung@laureateinstitute.org RI Furey, Maura/H-5273-2013; OI Nugent, Allison/0000-0003-2569-2480; Young, Kymberly/0000-0001-5133-2142 FU National Institutes of Health, National Institute of Mental Health (NIMH) [Z01-MH002792]; NIMH FX Grant support for the work was provided by the National Institutes of Health, National Institute of Mental Health (NIMH), via grant no. Z01-MH002792. The NIMH Division of Intramural Research Programs (DIRP) arranged peer review of the study design, provided IRB oversight of the data collection, management and analysis, and approved submission of the manuscript for publication. However, this sponsor did not influence directly the interpretation of the results or preparation of the manuscript.; We thank Dr Harvey Iwamoto for programming the AM task, Joan Williams and Michele Drevets for assistance with recruitment and clinical assessment of the participants, and Jeanette Black and Renee Hill for MRI technologist support. We also acknowledge the support of the NIMH Intramural Research Program. NR 59 TC 29 Z9 30 U1 5 U2 17 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 345 EP 357 DI 10.1017/S0033291711001371 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 886XL UT WOS:000299887700012 PM 21798113 ER PT J AU Magnusson, A Lundholm, C Goransson, M Copeland, W Heilig, M Pedersen, NL AF Magnusson, A. Lundholm, C. Goransson, M. Copeland, W. Heilig, M. Pedersen, N. L. TI Familial influence and childhood trauma in female alcoholism SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Alcohol dependence; childhood trauma; early onset; female twins; heritability ID CROSS-FOSTERING ANALYSIS; SUBSTANCE USE DISORDERS; SEXUAL-ABUSE; TWIN SAMPLE; WOMEN; ASSOCIATION; DEPENDENCE; ONSET; RISK; REPLICATION AB Background. To assess the role of genetic and environmental factors in female alcoholism using a large population-based twin sample, taking into account possible differences between early and late onset disease subtype. Method. Twins aged 20-47 years from the Swedish Twin Registry (n = 24 119) answered questions to establish lifetime alcohol use disorders. Subjects with alcoholism were classified for subtype. Structural equation modeling was used to quantify the proportion of phenotypic variance due to genetic and environmental factors and test whether heritability in women differed from that in men. The association between childhood trauma and alcoholism was then examined in females, controlling for background familial factors. Results. Lifetime prevalence of alcohol dependence was 4.9% in women and 8.6% in men. Overall, heritability for alcohol dependence was 55%, and did not differ significantly between men and women, although women had a significantly greater heritability for late onset (type I). Childhood physical trauma and sexual abuse had a stronger association with early onset compared to late onset alcoholism [odds ratio (OR) 2.54, 95% confidence interval (CI) 1.53-3.88 and OR 2.29, 95% CI 1.38-3.79 respectively]. Co-twin analysis indicated that familial factors largely accounted for the influence of physical trauma whereas the association with childhood sexual abuse reflected both familial and specific effects. Conclusions. Heritability of alcoholism in women is similar to that in men. Early onset alcoholism is strongly association with childhood trauma, which seems to be both a marker of familial background factors and a specific individual risk factor per se. Received 17 September 2010; Revised 20 June 2011; Accepted 25 June 2011; First published online 29 July 2011 C1 [Magnusson, A.; Goransson, M.; Heilig, M.] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Lundholm, C.; Pedersen, N. L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Copeland, W.] Duke Univ, Ctr Dev Epidemiol, Durham, NC USA. [Heilig, M.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. RP Magnusson, A (reprint author), Karolinska Univ Sjukhuset, BCS Ctr Dependence Disorders Stockholm I 66, S-14186 Stockholm, Sweden. EM asa.magnusson@sll.se RI copeland, william/N-5413-2014; OI Lundholm, Cecilia/0000-0002-6546-3650 FU Swedish Department of Higher Education; Swedish Research Council; AstraZeneca; County of Stockholm; National Institute on Alcohol Abuse and Alcoholism FX The Swedish Twin Registry is supported by grants from the Swedish Department of Higher Education and the Swedish Research Council, and an unrestricted research grant from AstraZeneca. This work was also supported by funding from the County of Stockholm and the National Institute on Alcohol Abuse and Alcoholism intramural research funds. NR 40 TC 10 Z9 10 U1 6 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD FEB PY 2012 VL 42 IS 2 BP 381 EP 389 DI 10.1017/S0033291711001310 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 886XL UT WOS:000299887700015 PM 21798111 ER PT J AU Dettmer, AM Novak, MA Suomi, SJ Meyer, JS AF Dettmer, Amanda M. Novak, Melinda A. Suomi, Stephen J. Meyer, Jerrold S. TI Physiological and behavioral adaptation to relocation stress in differentially reared rhesus monkeys: Hair cortisol as a biomarker for anxiety-related responses SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Hair; Cortisol; Infant; Early experience; Anxiety; Development ID CORTICOTROPIN-RELEASING-FACTOR; CSF MONOAMINE METABOLITE; CEREBROSPINAL-FLUID; NONHUMAN-PRIMATES; PLASMA-CORTISOL; MACACA-MULATTA; EMOTIONAL REACTIVITY; REARING EXPERIENCES; SEPARATION; NEUROENDOCRINE AB Increased hair cortisol concentrations have been associated with stress exposure in both human and nonhuman primates, and hair cortisol is now gaining attention as a biomarker for stress-related health problems. The present study examined the behavioral and physiological reactions of rhesus monkey (Macoca mulatto) infants reared in three different rearing environments to the major stressor of relocation. Infant monkeys (n = 61) were studied from birth through 2 years of age. For the first 8 months of life, infants were either with their mothers and peers (MPR, n = 21) or reared in a nursery using either peer-rearing (PR, n = 20) or surrogate-peer-rearing (SPR, n = 20). At approximately 8 months of age, infants were removed from their rearing group, simultaneously placed into a large social environment consisting of infants from all three rearing conditions, and observed for the next 16 months. Behavior was recorded twice per week from 1 to 24 months, and composite anxiety scores were calculated for each monkey. Monkeys were initially shaved at the nape of the neck on day 14 to remove any prenatal effects on hair cortisol deposition. Hair samples were then collected by re-shaving at 6, 12, 18 and 24 months and analyzed for cortisol content. MPR monkeys were the least affected by the stressor, showing smaller increases in anxious behavior than the other groups and more rapid physiological adaptation as assessed using hair cortisol. PR monkeys showed heightened and prolonged anxious behavior, had the highest cortisol levels prior to relocation, and their cortisol levels did not decline until more than a year later. SPR monkeys exhibited more rapid behavioral adaptation than PR monkeys, showing heightened but not prolonged anxious behavior. However, the SPR group showed a marked increase in cortisol in response to the relocation, and like the PR group, their physiological adaptation was slower than that of the MPR group as indicated by elevated cortisol levels at 18 months. By 24 months of age (16 months after relocation), all rearing groups were indistinguishable from one another physiologically and behaviorally. Spearman rank correlation revealed that hair cortisol taken at month 6 was not correlated with composite anxiety scores from months 6 to 8 (just before the relocation), but was positively correlated with composite anxiety scores between months 8 and 12 (immediately after relocation) for PR infants only (r(s) = 0.75, p < 0.001). Month 6-hair cortisol tended to positively correlate with composite anxiety scores for the following 6 months (months 12-18) for PR monkeys only (r(s), = 0.47, p = 0.037), which exhibited more anxious behavior than MPR and SPR infants during this period (ANOVA: F-(2,F-60) = 14.761, p < 0.001) This is the first study to show that elevated hair cortisol early in life is a biomarker for the later development of anxious behavior in response to a major life stressor, particularly for infant monkeys exposed to early life adversity in the form of peer-rearing. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Dettmer, Amanda M.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Novak, Melinda A.; Meyer, Jerrold S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Bethesda, MD USA. RP Dettmer, AM (reprint author), Univ Pittsburgh, Dept Psychiat, 3811 Ohara St, Pittsburgh, PA 15213 USA. EM ame48@pitt.edu OI Meyer, Jerrold/0000-0002-8382-7075 FU Division of Intramural Research, National Institute of Child Health Et Human Development, NIH; NIH [RR11122] FX This research was supported by funds from the Division of Intramural Research, National Institute of Child Health Et Human Development, NIH, and by NIH Grant RR11122 to M.A.N. Neither the NIH nor the NICHD had any further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 47 TC 44 Z9 45 U1 3 U2 27 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD FEB PY 2012 VL 37 IS 2 BP 191 EP 199 DI 10.1016/j.psyneuen.2011.06.003 PG 9 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 888BW UT WOS:000299979800003 PM 21715101 ER PT J AU Weber, R Weimar, C Wanke, I Moller-Hartmann, C Gizewski, ER Blatchford, J Hermansson, K Demchuk, AM Forsting, M Sacco, RL Saver, JL Warach, S Diener, HC Diehl, A AF Weber, Ralph Weimar, Christian Wanke, Isabel Moeller-Hartmann, Claudia Gizewski, Elke R. Blatchford, Jon Hermansson, Karin Demchuk, Andrew M. Forsting, Michael Sacco, Ralph L. Saver, Jeffrey L. Warach, Steven Diener, Hans Christoph Diehl, Anke CA PRoFESS Imaging Substudy Grp TI Risk of Recurrent Stroke in Patients With Silent Brain Infarction in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) Imaging Substudy SO STROKE LA English DT Article DE cerebral infarction; ischemic stroke; magnetic resonance imaging; mortality; silent brain infarction ID EXTENDED-RELEASE DIPYRIDAMOLE; ISCHEMIC-STROKE; TELMISARTAN; CLOPIDOGREL; POPULATION; PREVALENCE; MORTALITY; EVENTS; MRI AB Background and Purpose-Silent brain infarctions are associated with an increased risk of stroke in healthy individuals. Risk of recurrent stroke in patients with both symptomatic and silent brain infarction (SBI) has only been investigated in patients with cardioembolic stroke in the European Atrial Fibrillation Trial. We assessed whether patients with recent noncardioembolic stroke and SBI detected on MRI are at increased risk for recurrent stroke, other cardiovascular events, and mortality. Methods-The prevalence of SBI detected on MRI was assessed in 1014 patients enrolled in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The primary outcome was first recurrence of stroke in patients with both symptomatic stroke and SBI in comparison with age- and sex-matched patients with stroke without SBI. Secondary outcomes were a combined vascular end point, other vascular events, and mortality. The 2 groups were compared using conditional logistic regression. Results-Silent brain infarction was detected in 207 (20.4%) of the 1014 patients. Twenty-seven (13.0%) patients with SBI and 19 (9.2%) without SBI had a recurrent stroke (OR, 1.42; 95% CI, 0.79-2.56; P=0.24) during a mean follow-up of 2.5 years. Similarly, there was no statistically significant difference for all secondary outcome parameters between patients with SBI and matched patients without SBI. Conclusions-The presence of SBI in patients with recent mild noncardioembolic ischemic stroke could not be shown to be an independent risk factor for recurrent stroke, other vascular events, or a higher mortality rate. Clinical Trial Registration URL: http://clinicaltrials.gov. Unique identifier: NCT00153062. (Stroke. 2012;43:350-355.) C1 [Weber, Ralph; Weimar, Christian; Diener, Hans Christoph] Univ Duisburg Essen, Dept Neurol, D-45122 Essen, Germany. [Blatchford, Jon] Boehringer Ingelhelm Ltd, Bracknell, Berks, England. [Hermansson, Karin] Boehringer Ingelheim AB, Stockholm, Sweden. [Demchuk, Andrew M.] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary, AB, Canada. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Warach, Steven] NINDS, Stroke Diagnost & Therapeut Sect, NIH, Bethesda, MD 20892 USA. RP Diener, HC (reprint author), Univ Duisburg Essen, Dept Neurol, Hufelandstr 55, D-45122 Essen, Germany. EM hans.diener@uni-duisburg-essen.de RI bladin, chris/B-9136-2013; Forsting, Michael/C-6925-2013; Demchuk, Andrew/E-1103-2012; OI Demchuk, Andrew/0000-0002-4930-7789; Ringleb, Peter/0000-0002-5473-8671; Blatchford, Jon/0000-0001-9354-9657; Saver, Jeffrey/0000-0001-9141-2251 FU National Institute of Neurological Disorders and Stroke; Astra/Zeneca; GSK; Boehringer Ingelheim; Novartis; Janssen-Cilag; Sanofi-Aventis FX C.W. received honoraria for participation in clinical trials and contribution to advisory boards or oral presentations from Boehringer Ingelheim, Bristol-Myers Squib, Daiichi Asubio, Novartis, NovoNordisk, and Sanofi-Aventis. J.B. and K.H. are employees of Boehringer Ingelheim. A.M.D. received honoraria for contribution to advisory boards or oral presentations from Boehringer Ingelheim and Merck. R.L.S. received grants from the National Institute of Neurological Disorders and Stroke for the Northern Manhattan Study. He served as a consultant to Boehringer Ingelheim during the conduct of the PRoFESS trial. J.L.S. is an employee of the University of California, which received payments based on clinical trial contracts for the number of subjects enrolled from Boehringer Ingelheim and AGA Medical and received payments for faculty participation on scientific advisory boards from AGA Medical. H.C.D. received honoraria for participation in clinical trials and contribution to advisory boards or oral presentations from Abbott, AstraZeneca, Bayer Vital, BMS, Boehringer Ingelheim, CoAxia, D-Pharm, Fresenius, GlaxoSmithKline, Janssen-Cilag, MSD, MindFrame, Novartis, Novo-Nordisk, Paion, Parke-Davis, Pfizer, Sanofi-Aventis, Sankyo, Servier, Solvay, Thrombogenics, Wyeth, and Yamaguchi. He also received financial support for research projects provided by Astra/Zeneca, GSK, Boehringer Ingelheim, Novartis, Janssen-Cilag, and Sanofi-Aventis. A.D. received honoraria for contribution to advisory boards or oral presentations from Boehringer Ingelheim and Bristol-Myers-Squibb. NR 21 TC 8 Z9 10 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 350 EP 355 DI 10.1161/STROKEAHA.111.631739 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 885RK UT WOS:000299798300016 PM 22267825 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 Hallenbeck, JM AF Hallenbeck, John M. TI Tracks of a Non-Main Path Traveler 2011 Thomas Willis Lecture SO STROKE LA English DT Editorial Material DE animal models; basic science; brain infarction; endothelium; immunology; inflammation; risk factors ID CENTRAL-NERVOUS-SYSTEM; ISCHEMIC-STROKE; DECOMPRESSION-SICKNESS; MAMMALIAN HIBERNATION; CEREBRAL-ISCHEMIA; BLOOD-FLOW; BRAIN; NEUROPROTECTION; REPERFUSION; ACTIVATION AB After an unconventional beginning in stroke research, I veered off the main path repeatedly to view problems from a different perspective. In this lecture summary, I would like to return to several points along the byways that led to research with some continuity. (Stroke. 2012;43:585-590.) C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Hallenbeck, JM (reprint author), NINDS, Stroke Branch, NIH, 10 Ctr Dr,MSC 1401,Bldg 10,Room 5B02, Bethesda, MD 20892 USA. EM hallenbj@ninds.nih.gov FU Intramural NIH HHS [ZIA NS002924-16] NR 47 TC 0 Z9 0 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 585 EP 590 DI 10.1161/STROKEAHA.111.643668 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 885RK UT WOS:000299798300056 PM 22246691 ER PT J AU Hu, G Luo, J AF Hu, Guang Luo, Ji TI A primer on using pooled shRNA libraries for functional genomic screens SO ACTA BIOCHIMICA ET BIOPHYSICA SINICA LA English DT Review DE shRNA library; pooled screen; RNAi ID LENTIVIRAL RNAI LIBRARY; BREAST-CANCER; TUMOR SUPPRESSORS; MAMMALIAN-CELLS; GENETIC SCREEN; GROWTH ARREST; RAS ONCOGENE; IN-VIVO; INTERFERENCE; REGULATORS AB The discovery of RNA interference (RNAi) has revolutionized genetic analysis in mammalian cells. Loss-of-function RNAi screens enable rapid, functional annotation of the genome. Of the various RNAi approaches, pooled shRNA libraries have received considerable attention because of their versatility. A number of genome-wide shRNA libraries have been constructed against the human and mouse genomes, and these libraries can be readily applied to a variety of screens to interrogate the function of human and mouse genes in an unbiased fashion. We provide an introduction to the technical aspects of using pooled shRNA libraries for genetic screens. C1 [Hu, Guang] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Luo, Ji] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Luo, J (reprint author), NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. EM hug4@niehs.nih.gov; ji.luo@nih.gov RI Hu, Guang/E-7474-2016 OI Hu, Guang/0000-0003-0437-4723 FU National Institutes of Health of USA [Z01ES102745]; NCI-CCR at the US National Cancer Institute FX This work was supported by the grants from the National Institutes of Health Intramural Research Program of USA (Z01ES102745) (to G. H.) and the NCI-CCR intramural research program at the US National Cancer Institute (to J.L.). NR 45 TC 13 Z9 14 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1672-9145 J9 ACTA BIOCH BIOPH SIN JI Acta Biochim. Biophys. Sin. PD FEB PY 2012 VL 44 IS 2 BP 103 EP 112 DI 10.1093/abbs/gmr116 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 884YE UT WOS:000299744000001 PM 22271906 ER PT J AU Brzezinski, K Dauter, Z Jaskolski, M AF Brzezinski, Krzysztof Dauter, Zbigniew Jaskolski, Mariusz TI Structures of NodZ a1,6-fucosyltransferase in complex with GDP and GDP-fucose SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article DE glycosyltransferases; fucosyltransferases; family GT-23 glycosyltransferases; chitooligosaccharide fucosylation; Nod-factor biosynthesis; nodulation; Nod factors; legume-rhizobium symbiosis; nitrogen fixation ID CRYSTAL-STRUCTURE; MAMMALIAN ALPHA-1,6-FUCOSYL-TRANSFERASE; RHIZOBIUM-LEGUMINOSARUM; ACETYL TRANSFERASE; NODULATION SIGNAL; ROOT NODULATION; GLYCOSYLTRANSFERASES; BIOSYNTHESIS; MECHANISM; PROTEIN AB Rhizobial NodZ a1,6-fucosyltransferase (a1,6-FucT) catalyzes the transfer of the fucose (Fuc) moiety from guanosine 5'-diphosphate-beta-l-fucose to the reducing end of the chitin oligosaccharide core during Nod-factor (NF) biosynthesis. NF is a key signalling molecule required for successful symbiosis with a legume host for atmospheric nitrogen fixation. To date, only two a1,6-FucT structures have been determined, both without any donor or acceptor molecule that could similar to highlight the structural background of the catalytic mechanism. Here, the first crystal structures of a1,6-FucT in complex with its substrate GDP-Fuc and with GDP, which is similar to a similar to byproduct of the enzymatic reaction, are presented. The crystal of the complex with GDP-Fuc was obtained through soaking of native NodZ crystals with the ligand and its structure has been determined at 2.35 angstrom resolution. The fucose residue is exposed to solvent and is disordered. The enzymeproduct complex crystal was obtained by cocrystallization with GDP and an acceptor molecule, penta-N-acetyl-l-glucosamine (penta-NAG). The structure has been determined at 1.98 angstrom resolution, showing that only the GDP molecule is present in the complex. In both structures the ligands are located in a cleft formed between the two domains of NodZ and extend towards the C-terminal domain, but their conformations differ significantly. The structures revealed that residues in three regions of the C-terminal domain, which are conserved among a1,2-, a1,6- and protein O-fucosyltransferases, are involved in interactions with the sugar-donor molecule. There is also an interaction with the side chain of Tyr45 in the N-terminal domain, which is very unusual for a GT-B-type glycosyltransferase. Only minor conformational changes of the protein backbone are observed upon ligand binding. The only exception is a movement of the loop located between strand beta C2 and helix aC3. In addition, there is a shift of the aC3 helix itself upon GDP-Fuc binding. C1 [Brzezinski, Krzysztof; Jaskolski, Mariusz] Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, PL-61704 Poznan, Poland. [Brzezinski, Krzysztof; Dauter, Zbigniew] Argonne Natl Lab, Synchrotron Radiat Res Sect, MCL, NCI, Argonne, IL 60439 USA. [Jaskolski, Mariusz] Adam Mickiewicz Univ, Dept Crystallog, Fac Chem, PL-60780 Poznan, Poland. RP Jaskolski, M (reprint author), Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, PL-61704 Poznan, Poland. EM mariuszj@amu.edu.pl FU Polish Ministry of Science and Higher Education [N N302 4305 34]; NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN2612008000001E]; National Center for Research Resources at the National Institutes of Health [RR-15301]; US Department of Energy, Office of Basic Energy Sciences [W-31-109-Eng-38] FX This work was supported in part by a grant from the Polish Ministry of Science and Higher Education (No. N N302 4305 34), by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research and by Federal funds from the National Cancer Institute, National Institutes of Health under Contract HHSN2612008000001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government. Use of the SER-CAT beamline was supported by award RR-15301 from the National Center for Research Resources at the National Institutes of Health and the use of the Advanced Photon Source was supported by the US Department of Energy, Office of Basic Energy Sciences under Contract No. W-31-109-Eng-38. NR 48 TC 5 Z9 6 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD FEB PY 2012 VL 68 BP 160 EP 168 DI 10.1107/S0907444911053157 PN 2 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 881FX UT WOS:000299469100009 PM 22281745 ER PT J AU Babitz, S AF Babitz, Shuly TI In Memory of Morris E. Chafetz, MD, 1924-2011 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Biographical-Item C1 NIAAA, Bethesda, MD 20892 USA. RP Babitz, S (reprint author), NIAAA, 5635 Fishers Lane, Bethesda, MD 20892 USA. EM shuly.babitz@nih.gov 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2012 VL 36 IS 2 BP 191 EP 192 DI 10.1111/j.1530-0277.2011.01733.x PG 2 WC Substance Abuse SC Substance Abuse GA 883DS UT WOS:000299614700001 ER PT J AU Vatsalya, V Issa, JE Hommer, DW Ramchandani, VA AF Vatsalya, Vatsalya Issa, Julnar E. Hommer, Daniel W. Ramchandani, Vijay A. TI Pharmacodynamic Effects of Intravenous Alcohol on Hepatic and Gonadal Hormones: Influence of Age and Sex SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Age; Alcohol; Estradiol; Growth Hormone; IGF-1; Sex; Testosterone ID GROWTH-FACTOR-I; PREMENOPAUSAL WOMEN; LUTEINIZING-HORMONE; GENE-EXPRESSION; CHRONIC ETHANOL; TESTOSTERONE; SECRETION; MEN; PLASMA; ELIMINATION AB Background: Growth hormone (GH)insulin-like growth factor-1 (IGF-1) axis and gonadal hormones demonstrate extensively associated regulation; however, little is known about the effects of acute alcohol exposure on these hormones. This study examined the effects of intravenous alcohol on the GHIGF-1 axis and gonadal hormone concentrations, and the influence of age and sex on their regulation. Methods: Forty-eight healthy volunteers (24 men and 24 women each in the 21 to 25 and 55 to 65 year age groups) underwent a 2-session single-blinded study. Subjects received in randomized counter-balanced order, alcohol infusions, individually computed based on a physiologically based pharmacokinetic model, to maintain a steady-state ("clamped") exposure of 50 mg% or saline for 3 hours in separate sessions. Blood samples collected at baseline and postinfusion in each session were assayed for levels of GH, IGF-1, free testosterone, and estradiol. Results: Acute alcohol administration resulted in changes in gonadal hormones that differed by sex. Change in free testosterone showed a significant treatment x baseline interaction (p < 0.001), indicating that alcohol-induced suppression of testosterone occurred predominantly in men. On the other hand, change in estradiol showed a significant treatment x sex interaction (p = 0.028), indicating that alcohol-induced increases in estradiol occurred predominantly in women. There was a trend for alcohol-induced decreases in IGF-1 levels. Change in GH showed a significant main effect of baseline (p < 0.001) and a trend for treatment by baseline interaction, suggesting an alcohol-induced decrease in individuals with high baseline GH values. There was also a significant main effect of sex (p = 0.046) indicating that men had greater changes in GH across treatment compared with women. Conclusions: Alcohol induced a complex pattern of hormonal responses that varied between younger and older men and women. Some of the observed sex-based differences may help improve our understanding of the greater susceptibility to alcohol-related hepatic damage seen in women. C1 [Vatsalya, Vatsalya; Issa, Julnar E.; Ramchandani, Vijay A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. [Hommer, Daniel W.] NIAAA, Lab Clin & Translat Studies, Sect Brain Electrophysiol & Imaging, Bethesda, MD 20892 USA. RP Vatsalya, V (reprint author), NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, 10 Ctr Dr,Room 2-2352, Bethesda, MD 20892 USA. EM vijayr@mail.nih.gov FU Intramural NIH HHS [ZIA AA000466-06, ZIA AA000466-07] NR 37 TC 11 Z9 11 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2012 VL 36 IS 2 BP 207 EP 213 DI 10.1111/j.1530-0277.2011.01600.x PG 7 WC Substance Abuse SC Substance Abuse GA 883DS UT WOS:000299614700004 PM 21797891 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 Snell, LD Ramchandani, VA Saba, L Herion, D Heilig, M George, DT Pridzun, L Helander, A Schwandt, ML Phillips, MJ Hoffman, PL Tabakoff, B AF Snell, Lawrence D. Ramchandani, Vijay A. Saba, Laura Herion, David Heilig, Markus George, David T. Pridzun, Lutz Helander, Anders Schwandt, Melanie L. Phillips, Monte J. Hoffman, Paula L. Tabakoff, Boris CA WHO ISBRA Study State Trait TI The Biometric Measurement of Alcohol Consumption SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Consumption; Biomarkers; MAO Protein; Platelets ID PLATELET MONOAMINE-OXIDASE; CARBOHYDRATE-DEFICIENT TRANSFERRIN; TRAIT MARKERS; SMOKING; DEPENDENCE; DRINKING; PERSONALITY; INHIBITION; DISORDERS; WHO/ISBRA AB Background: Proper ascertainment of the history of alcohol consumption by an individual is an important component of medical diagnosis of disease and influences the implementation of appropriate treatment strategies that include prescription of medication, as well as intervention for the negative physical and social consequences of hazardous/harmful levels of alcohol consumption. Biological (biometric) diagnostic tests that provide information on current and past quantity and frequency of alcohol consumption by an individual, prior to onset of organ damage, continue to be sought. Methods: Platelet monoamine oxidase B (MAO-B) protein was quantitated in 2 populations of subjects who had histories of different levels of alcohol consumption. Levels were assayed by immunoblotting or by ELISA. The development and evaluation of the new ELISA-based measure of platelet MAO-B protein levels is described. Results: One subject population constituted a nontreatment-seeking, cross-sectional subject sample, and the other population was a longitudinally followed, hospitalized group of subjects. An algorithm combining measures of platelet MAO-B protein with the plasma levels of carbohydrate-deficient transferrin (CDT) and with liver enzymes (aspartate aminotransferase or gamma-glutamyltransferase [GGT]) can detect hazardous/harmful alcohol use (HHAU) with the highest sensitivity and specificity in the cross-sectional nontreatment-seeking population. In the treatment-seeking population, low MAO-B protein levels at admission are associated with heavy drinking prior to admission, and these protein levels increase over a period of abstinence from alcohol. Conclusions: The platelet MAO-B protein measurement is particularly effective for male alcohol consumers. The combined use of MAO-B protein measures together with measures of CDT and GGT does, however, improve the diagnostic utility of both markers for ascertaining HHAU in women. Furthermore, measurement of changes in platelet MAO-B protein levels during treatment for alcohol dependence may help monitor the success of the treatment program. C1 [Saba, Laura; Hoffman, Paula L.; Tabakoff, Boris] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA. [Snell, Lawrence D.; Tabakoff, Boris] Lohocla Res Corp, Aurora, CO USA. [Ramchandani, Vijay A.; Herion, David; Heilig, Markus; George, David T.; Schwandt, Melanie L.; Phillips, Monte J.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. [Pridzun, Lutz] Mediagnost GmbH, Reutlingen, Germany. [Helander, Anders] Karolinska Inst, Dept Lab Med, Stockholm, Sweden. RP Tabakoff, B (reprint author), Univ Colorado, Sch Med, Dept Pharmacol, MS 8303,POB 6511,12800 E,19th Ave, Aurora, CO 80045 USA. EM boris.tabakoff@ucdenver.edu RI Schwandt, Melanie/L-9866-2016; OI Heilig, Markus/0000-0003-2706-2482; Saba, Laura/0000-0001-9649-1294 FU Lohocla Research Corporation [R44AA014531, R43AA017374]; Banbury Fund; WHO/ISBRA FX Funding for Lohocla Research Corporation: SBIR grants R44AA014531 and R43AA017374 and the Banbury Fund. Mediagnost thanks Nadine Wachendorfer for her excellent technical assistance. This work is in part a result of the work of WHO/ISBRA Investigators: K.M. Conigrave, M. Dongier, H. Edenberg, C.J.P. Eriksson, M.L.O.S. Formigoni, B.F. Grant, A. Helander, P.L. Hoffman, K. Kiianmaa, T. Koyama, L. Legault, T.-K. Li, T. Mathuen, M.G. Monteiro, T. Saito, M. Salaspuro, J.B. Saunders, B. Tabakoff, S. Tufik, J.B. Whitfield, and F.M. Wurst. NR 32 TC 5 Z9 5 U1 0 U2 4 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 332 EP 341 DI 10.1111/j.1530-0277.2011.01605.x PG 10 WC Substance Abuse SC Substance Abuse GA 883DS UT WOS:000299614700020 PM 21895709 ER PT J AU Mukherjee, B Ahn, J Gruber, SB Chatterjee, N AF Mukherjee, Bhramar Ahn, Jaeil Gruber, Stephen B. Chatterjee, Nilanjan TI Testing Gene-Environment Interaction in Large-Scale Case-Control Association Studies: Possible Choices and Comparisons SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; efficiency; familywise error rate; genome-wide association study; profile likelihood; robustness; shrinkage ID GENOME-WIDE ASSOCIATION; BREAST-CANCER RISK; MAXIMUM-LIKELIHOOD; INDEPENDENCE; MODELS; GENOTYPE; EXPOSURE; DESIGNS; POWER; BIAS AB Several methods for screening gene-environment interaction have recently been proposed that address the issue of using gene-environment independence in a data-adaptive way. In this report, the authors present a comparative simulation study of power and type I error properties of 3 classes of procedures: 1) the standard 1-step case-control method; 2) the case-only method that requires an assumption of gene-environment independence for the underlying population; and 3) a variety of hybrid methods, including empirical-Bayes, 2-step, and model averaging, that aim at gaining power by exploiting the assumption of gene-environment independence and yet can protect against false positives when the independence assumption is violated. These studies suggest that, although the case-only method generally has maximum power, it has the potential to create substantial false positives in large-scale studies even when a small fraction of markers are associated with the exposure under study in the underlying population. All the hybrid methods perform well in protecting against such false positives and yet can retain substantial power advantages over standard case-control tests. The authors conclude that, for future genome-wide scans for gene-environment interactions, major power gain is possible by using alternatives to standard case-control analysis. Whether a case-only type scan or one of the hybrid methods should be used depends on the strength and direction of gene-environment interaction and association, the level of tolerance for false positives, and the nature of replication strategies. C1 [Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Mukherjee, Bhramar; Ahn, Jaeil] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Gruber, Stephen B.] Univ Michigan, Dept Internal Med Human Genet & Epidemiol, Ann Arbor, MI 48109 USA. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd, Rockville, MD 20852 USA. EM chattern@mail.nih.gov FU National Institutes of Health [CA-156608, U19 NCI-895700]; National Science Foundation [DMS-1007494]; National Cancer Institute FX This research was partially supported by National Institutes of Health grant CA-156608 and National Science Foundation grant DMS-1007494 to B. M., National Institutes of Health grant U19 NCI-895700 to S. B. G. and B. M., and the Intramural Research Program of the National Cancer Institute to N. C. NR 32 TC 50 Z9 50 U1 1 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2012 VL 175 IS 3 BP 177 EP 190 DI 10.1093/aje/kwr367 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 882XC UT WOS:000299596200003 PM 22199027 ER PT J AU Cornelis, MC Tchetgen, EJT Liang, LM Qi, L Chatterjee, N Hu, FB Kraft, P AF Cornelis, Marilyn C. Tchetgen, Eric J. Tchetgen Liang, Liming Qi, Lu Chatterjee, Nilanjan Hu, Frank B. Kraft, Peter TI Gene-Environment Interactions in Genome-Wide Association Studies: A Comparative Study of Tests Applied to Empirical Studies of Type 2 Diabetes SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; case study; diabetes mellitus; type 2; epidemiologic methods; genome-wide association study; genotype-environment interaction ID RANDOM FORESTS; DESIGNS; SUSCEPTIBILITY; INDEPENDENCE; DEFINITIONS; INFERENCE; VARIANTS; DISEASES; MODELS; POWER AB The question of which statistical approach is the most effective for investigating gene-environment (G-E) interactions in the context of genome-wide association studies (GWAS) remains unresolved. By using 2 case-control GWAS (the Nurses' Health Study, 1976-2006, and the Health Professionals Follow-up Study, 1986-2006) of type 2 diabetes, the authors compared 5 tests for interactions: standard logistic regression-based case-control; case-only; semiparametric maximum-likelihood estimation of an empirical-Bayes shrinkage estimator; and 2-stage tests. The authors also compared 2 joint tests of genetic main effects and G-E interaction. Elevated body mass index was the exposure of interest and was modeled as a binary trait to avoid an inflated type I error rate that the authors observed when the main effect of continuous body mass index was misspecified. Although both the case-only and the semiparametric maximum-likelihood estimation approaches assume that the tested markers are independent of exposure in the general population, the authors did not observe any evidence of inflated type I error for these tests in their studies with 2,199 cases and 3,044 controls. Both joint tests detected markers with known marginal effects. Loci with the most significant G-E interactions using the standard, empirical-Bayes, and 2-stage tests were strongly correlated with the exposure among controls. Study findings suggest that methods exploiting G-E independence can be efficient and valid options for investigating G-E interactions in GWAS. C1 [Cornelis, Marilyn C.; Qi, Lu; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Tchetgen, Eric J. Tchetgen; Liang, Liming; Hu, Frank B.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tchetgen, Eric J. Tchetgen; Liang, Liming; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Qi, Lu; Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Qi, Lu; Hu, Frank B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP Cornelis, MC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM mcomeli@hsph.harvard.edu FU National Institutes of Health (NIH) Genes, Environment, and Health Initiative (GEI) [U01HG-004738, U01HG004422, U01HG004402, U01HG004729, U01HG004726, U01HG004735, U01HG004415, U01HG-004436, U01HG004423, U01HG004728, RFAHG006033]; NIH (National Institute of Dental and Craniofacial Research) [U01DE018993, U01DE018903]; NIH (National Institute on Alcohol Abuse and Alcoholism) [U10AA008401]; NIH (National Institute on Drug Abuse) [P01CA089392, R01DA013423]; NIH (National Cancer Institute) [CA63464, CA54281, CA 136792, Z01CP010200]; NIH GEI [U01HG04424, U01HG004438]; Johns Hopkins University Center for Inherited Disease Research; NIH [HHSN-268200782096C, 1R21 ES019712-01]; National Cancer Institute [P01CA087969, P01CA055075]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK058845]; Canadian Institutes of Health Research FX The Nurses' Health Study/Health Professionals Follow-up Study Type 2 Diabetes GWAS (U01HG004399) is a component of a collaborative project that includes 13 other GWAS funded as part of the Gene-Environment Association Studies (GENEVA) under the National Institutes of Health (NIH) Genes, Environment, and Health Initiative (GEI) (U01HG-004738, U01HG004422, U01HG004402, U01HG004729, U01HG004726, U01HG004735, U01HG004415, U01HG-004436, U01HG004423, U01HG004728, RFAHG006033), with additional support from individual institutes of the NIH (National Institute of Dental and Craniofacial Research: U01DE018993, U01DE018903; National Institute on Alcohol Abuse and Alcoholism: U10AA008401; National Institute on Drug Abuse: P01CA089392, R01DA013423; and National Cancer Institute: CA63464, CA54281, CA 136792, Z01CP010200). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the Coordinating Center of the Gene-Environment Association Studies (U01HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Genotyping was performed at the Broad Institute of the Massachusetts Institute of Technology and Harvard, with funding support from the NIH GEI (U01HG04424), and Johns Hopkins University Center for Inherited Disease Research, with support from the NIH GEI (U01HG004438) and an NIH contract (HHSN-268200782096C). Additional funding for the current research was provided by the NIH (1R21 ES019712-01), the National Cancer Institute (P01CA087969, P01CA055075), and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845). M. C. C. is a recipient of a Canadian Institutes of Health Research Fellowship. NR 40 TC 45 Z9 45 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2012 VL 175 IS 3 BP 191 EP 202 DI 10.1093/aje/kwr368 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 882XC UT WOS:000299596200004 PM 22199026 ER PT J AU Mukherjee, B Ahn, J Gruber, SB Chatterjee, N AF Mukherjee, Bhramar Ahn, Jaeil Gruber, Stephen B. Chatterjee, Nilanjan TI Mukherjee et al. Respond to "GE-Whiz! Ratcheting Up Gene-Environment Studies" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material C1 [Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Mukherjee, Bhramar; Ahn, Jaeil] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Gruber, Stephen B.] Univ Michigan, Dept Internal Med Human Genet & Biostat, Ann Arbor, MI 48109 USA. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd, Rockville, MD 20852 USA. EM chattern@mail.nih.gov NR 6 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2012 VL 175 IS 3 BP 208 EP 209 DI 10.1093/aje/kwr366 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 882XC UT WOS:000299596200006 ER PT J AU Hall, KL Stokols, D Stipelman, BA Vogel, AL Feng, A Masimore, B Morgan, G Moser, RP Marcus, SE Berrigan, D AF Hall, Kara L. Stokols, Daniel Stipelman, Brooke A. Vogel, Amanda L. Feng, Annie Masimore, Beth Morgan, Glen Moser, Richard P. Marcus, Stephen E. Berrigan, David TI Assessing the Value of Team Science A Study Comparing Center- and Investigator-Initiated Grants SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID TRANSDISCIPLINARY RESEARCH; HEALTH; COLLABORATION; READINESS; OUTCOMES; ADDRESS AB Background: Large cross-disciplinary scientific teams are becoming increasingly prominent in the conduct of research. Purpose: This paper reports on a quasi-experimental longitudinal study conducted to compare bibliometric indicators of scientific collaboration, productivity, and impact of center-based transdisciplinary team science initiatives and traditional investigator-initiated grants in the same field. Methods: All grants began between 1994 and 2004 and up to 10 years of publication data were collected for each grant. Publication information was compiled and analyzed during the spring and summer of 2010. Results: Following an initial lag period, the transdisciplinary research center grants had higher overall publication rates than the investigator-initiated R01 (NIH Research Project Grant Program) grants. There were relatively uniform publication rates across the research center grants compared to dramatically dispersed publication rates among the R01 grants. On average, publications produced by the research center grants had greater numbers of coauthors but similar journal impact factors compared with publications produced by the R01 grants. Conclusions: The lag in productivity among the transdisciplinary center grants was offset by their overall higher publication rates and average number of coauthors per publication, relative to investigator-initiated grants, over the 10-year comparison period. The findings suggest that transdisciplinary center grants create benefits for both scientific productivity and collaboration. (Am J Prev Med 2012; 42(2): 157-163) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Hall, Kara L.; Stipelman, Brooke A.; Morgan, Glen; Moser, Richard P.; Berrigan, David] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Marcus, Stephen E.] Natl Inst Gen Med Sci, Ctr Bioinformat & Computat Biol, NIH, Bethesda, MD USA. [Vogel, Amanda L.] SAIC Frederick Inc, NCI Frederick, Clin Res Directorate CMRP, Frederick, MD USA. [Masimore, Beth] Discovery Log, Rockville, MD USA. [Stokols, Daniel] Univ Calif Irvine, Sch Social Ecol, Irvine, CA USA. [Feng, Annie] Feng Consulting, Livingston, NJ USA. RP Hall, KL (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7338,Execut Plaza N,Room 407, Bethesda, MD 20892 USA. EM hallka@mail.nih.gov FU National Cancer Institute, NIH [HHSN261200800001E]; [HHSN-276-2007-00235U] FX We thank James Corrigan (NCI), Lawrence Solomon (NCI), Joshua Schnell (Discovery Logic Inc.), and Laurel Haak (Discovery Logic Inc.) for their assistance and helpful comments in the preparation of this manuscript. This work was supported by contract number HHSN-276-2007-00235U. This project was funded, in whole or in part, with federal funds from the National Cancer Institute, NIH, under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the DHHS, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. NR 38 TC 40 Z9 43 U1 1 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD FEB PY 2012 VL 42 IS 2 BP 157 EP 163 DI 10.1016/j.amepre.2011.10.011 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 879DQ UT WOS:000299310300007 PM 22261212 ER PT J AU Hyvonen, MT Keinanen, TA Khomutov, M Simonian, A Vepsalainen, J Park, JH Khomutov, AR Alhonen, L Park, MH AF Hyvonen, Mervi T. Keinanen, Tuomo A. Khomutov, Maxim Simonian, Alina Vepsalainen, Jouko Park, Jong Hwan Khomutov, Alex R. Alhonen, Leena Park, Myung Hee TI Effects of novel C-methylated spermidine analogs on cell growth via hypusination of eukaryotic translation initiation factor 5A SO AMINO ACIDS LA English DT Article DE Polyamine; Methylated spermidine; Cell growth; Deoxyhypusine synthase; Hypusine; eIF5A ID YEAST SACCHAROMYCES-CEREVISIAE; DEOXYHYPUSINE SYNTHASE ACTIVITY; POLYAMINE METABOLISM; POSTTRANSLATIONAL SYNTHESIS; AMINO-ACID; PROTEIN; INHIBITION; CYTOSTASIS; VIABILITY; DEPLETION AB The polyamines, putrescine, spermidine, and spermine, are ubiquitous multifunctional cations essential for cellular proliferation. One specific function of spermidine in cell growth is its role as a butylamine donor for hypusine synthesis in the eukaryotic initiation factor 5A (eIF5A). Here, we report the ability of novel mono-methylated spermidine analogs (alpha-MeSpd, beta-MeSpd, gamma-MeSpd, and omega-MeSpd) to function in the hypusination of eIF5A and in supporting the growth of DFMO-treated DU145 cells. We also tested them as substrates and inhibitors for deoxyhypusine synthase (DHS) in vitro. Of these compounds, alpha-MeSpd, beta-MeSpd, and gamma-MeSpd (but not omega-MeSpd) were substrates for DHS in vitro, while they all inhibited the enzyme reaction. As racemic mixtures, only alpha-MeSpd and beta-MeSpd supported long-term growth (9-18 days) of spermidine-depleted DU145 cells, whereas gamma-MeSpd and omega-MeSpd did not. The S-enantiomer of alpha-MeSpd, which supported long-term growth, was a good substrate for DHS in vitro, whereas the R-isomer was not. The long-term growth of DFMO-treated cells correlated with the hypusine modification of eIF5A by intracellular methylated spermidine analogs. These results underscore the critical requirement for hypusine modification in mammalian cell proliferation and provide new insights into the specificity of the deoxyhypusine synthase reaction. C1 [Hyvonen, Mervi T.; Alhonen, Leena] Univ Eastern Finland, Bioctr Kuopio, AI Virtanen Inst Mol Sci, Kuopio 70210, Finland. [Keinanen, Tuomo A.; Vepsalainen, Jouko] Univ Eastern Finland, Bioctr Kuopio, Chem Lab, Dept Biosci, Kuopio 70210, Finland. [Khomutov, Maxim; Simonian, Alina; Khomutov, Alex R.] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow 119991, Russia. [Park, Jong Hwan; Park, Myung Hee] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Hyvonen, MT (reprint author), Univ Eastern Finland, Bioctr Kuopio, AI Virtanen Inst Mol Sci, Yliopistonranta 1E, Kuopio 70210, Finland. EM mervi.hyvonen@uef.fi; mhpark@nih.gov RI khomutov, maxim/G-2234-2015; OI Keinanen, Tuomo/0000-0002-0659-5573 FU National Institute of Dental and Craniofacial Research (NIDCR), NIH; Academy of Finland; Russian Foundation for Basic Research [09-04-01272]; Presidium of the Russian Academy of Sciences; Finnish Cultural Foundation; University of Eastern Finland FX The research was supported in part by the Intramural Research Program of National Institute of Dental and Craniofacial Research (NIDCR), NIH and by grants from the Academy of Finland, the Russian Foundation for Basic Research [grant number 09-04-01272], the program Molecular and Cell Biology of the Presidium of the Russian Academy of Sciences, the North Savo Regional Fund of the Finnish Cultural Foundation and by the University of Eastern Finland (Novel Materials, Technologies and Drug Molecules Based on Phosphorus and/or Nitrogen Compounds; JV/TAK). The authors thank Ms. Sisko Juutinen, Ms. Anne Karppinen, Ms Arja Korhonen, and Ms. Tuula Reponen for skillful technical assistance and Dr. Edith C. Wolff (NIDCR, NIH) for critical reading of the manuscript and helpful suggestions. NR 40 TC 9 Z9 10 U1 0 U2 8 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD FEB PY 2012 VL 42 IS 2-3 BP 685 EP 695 DI 10.1007/s00726-011-0984-1 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 881RT UT WOS:000299506000026 PM 21861168 ER PT J AU Dias, CAO Gregio, APB Rossi, D Galvao, FC Watanabe, TF Park, MH Valentini, SR Zanelli, CF AF Dias, Camila A. O. Borges Gregio, Ana Paula Rossi, Danuza Galvao, Fabio Carrilho Watanabe, Tatiana F. Park, Myung Hee Valentini, Sandro R. Zanelli, Cleslei F. TI eIF5A interacts functionally with eEF2 SO AMINO ACIDS LA English DT Article DE eIF5A; Hypusine; eEF2; Translation elongation ID INITIATION-FACTOR 5A; PROMOTES TRANSLATION ELONGATION; SACCHAROMYCES-CEREVISIAE; PROTEIN-SYNTHESIS; HYPUSINE MODIFICATION; YEAST; GROWTH; PROLIFERATION; REVEAL; MUTANT AB eIF5A is highly conserved from archaea to mammals, essential for cell viability and the only protein known to contain the essential amino acid residue hypusine, generated by a unique posttranslational modification. eIF5A was originally identified as a translation initiation factor due to its ability to stimulate the formation of the first peptide bond. However, recent studies have shown that depletion of eIF5A causes a significant decrease in polysome run-off and an increase in the ribosome transit time, suggesting that eIF5A is actually involved in the elongation step of protein synthesis. We have previously shown that the depletion mutant tif51A-3 (eIF5A(C39Y/G118D)) shows a sicker phenotype when combined with the dominant negative mutant eft2 (H699K) of the elongation factor eEF2. In this study, we used the eIF5A(K56A) mutant to further investigate the relationship between eIF5A and eEF2. The eIF5A(K56A) mutant is temperature sensitive and has a defect in protein synthesis, but instead of causing depletion of the eIF5A protein, this mutant has a defect in hypusine modification. Like the mutant tif51A-3, the eIF5A(K56A) mutant is synthetic sick with the mutant eft2 (H699K) of eEF2. High-copy eEF2 not only improves cell growth of the eIF5A(K56A) mutant, but also corrects its increased cell size defect. Moreover, eEF2 suppression of the eIF5A(K56A) mutant is correlated with the improvement of total protein synthesis and with the increased resistance to the protein synthesis inhibitor hygromycin B. Finally, the polysome profile defect of the eIF5A(K56A) mutant is largely corrected by high-copy eEF2. Therefore, these results demonstrate that eIF5A is closely related to eEF2 function during translation elongation. C1 [Dias, Camila A. O.; Borges Gregio, Ana Paula; Rossi, Danuza; Galvao, Fabio Carrilho; Watanabe, Tatiana F.; Valentini, Sandro R.; Zanelli, Cleslei F.] UNESP Univ Estadual Paulista, Sch Pharmaceut Sci, Dept Biol Sci, Araraquara, SP, Brazil. [Park, Myung Hee] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Zanelli, CF (reprint author), UNESP Univ Estadual Paulista, Sch Pharmaceut Sci, Dept Biol Sci, Araraquara, SP, Brazil. EM zanellicf@fcfar.unesp.br RI Valentini, Sandro/C-4353-2012; Dias, Camila/G-3494-2012; zanelli, cleslei/C-1916-2013; Inov Farmaceutica, Inct/K-2313-2013 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); PADC from Faculdade de Ciencias Farmaceuticas, UNESP; CAPES FX This work was supported by grants to S.R.V. from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and PADC from Faculdade de Ciencias Farmaceuticas, UNESP. We also thank FAPESP, CNPq and CAPES for fellowships awarded to most of the authors (C. A. O. D.; A. P. B. G.; D. R.; F. C. G. and T. F. W.). NR 28 TC 13 Z9 17 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD FEB PY 2012 VL 42 IS 2-3 BP 697 EP 702 DI 10.1007/s00726-011-0985-0 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 881RT UT WOS:000299506000027 PM 21822730 ER PT J AU Nishimura, K Lee, SB Park, JH Park, MH AF Nishimura, Kazuhiro Lee, Seung Bum Park, Jong Hwan Park, Myung Hee TI Essential role of eIF5A-1 and deoxyhypusine synthase in mouse embryonic development SO AMINO ACIDS LA English DT Article DE eIF5A; Hypusine; Polyamine; Spermidine; Deoxyhypusine synthase; Gene knockout ID INITIATION-FACTOR 5A; TRANSLATION INITIATION; HYPUSINE MODIFICATION; AMINO-ACID; POSTTRANSLATIONAL SYNTHESIS; CELL-CYCLE; PROTEIN; YEAST; INHIBITION; EXPRESSION AB The eukaryotic initiation factor 5A (eIF5A) contains a polyamine-derived amino acid, hypusine [N-epsilon-(4-amino-2-hydroxybutyl)lysine]. Hypusine is formed post-translationally by the addition of the 4-aminobutyl moiety from the polyamine spermidine to a specific lysine residue, catalyzed by deoxyhypusine synthase (DHPS), and subsequent hydroxylation by deoxyhypusine hydroxylase (DOHH). The eIF5A precursor protein and both of its modifying enzymes are highly conserved, suggesting a vital cellular function for eIF5A and its hypusine modification. To address the functions of eIF5A and the first modification enzyme, DHPS, in mammalian development, we knocked out the Eif5a or the Dhps gene in mice. Eif5a heterozygous knockout mice and Dhps heterozygous knockout mice were viable and fertile. However, homozygous Eif5a1 (gt/gt) embryos and Dhps (gt/gt) embryos died early in embryonic development, between E3.5 and E7.5. Upon transfer to in vitro culture, homozygous Eif5a (gt/gt) or Dhps (gt/gt) blastocysts at E3.5 showed growth defects when compared to heterozygous or wild type blastocysts. Thus, the knockout of either the eIF5A-1 gene (Eif5a) or of the deoxyhypusine synthase gene (Dhps) caused early embryonic lethality in mice, indicating the essential nature of both eIF5A-1 and deoxyhypusine synthase in mammalian development. C1 [Nishimura, Kazuhiro; Lee, Seung Bum; Park, Jong Hwan; Park, Myung Hee] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Park, MH (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bldg 30,Room 211, Bethesda, MD 20892 USA. EM mhpark@nih.gov FU National Institute of Dental and Craniofacial Research (NIDCR) NIH; KANAE Foundation for the Promotion of Medical Science (Japan) FX The research was supported in part by the Intramural Research Program of National Institute of Dental and Craniofacial Research (NIDCR) NIH and KANAE Foundation for the Promotion of Medical Science (Japan). We thank Dr. Edith C. Wolff (NIDCR, NIH) for critical reading of the manuscript and helpful suggestions. NR 37 TC 33 Z9 33 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD FEB PY 2012 VL 42 IS 2-3 BP 703 EP 710 DI 10.1007/s00726-011-0986-z PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 881RT UT WOS:000299506000028 PM 21850436 ER PT J AU Chen, CZ Sobczak, K Hoskins, J Southall, N Marugan, JJ Zheng, W Thornton, CA Austin, CP AF Chen, Catherine Z. Sobczak, Krzysztof Hoskins, Jason Southall, Noel Marugan, Juan J. Zheng, Wei Thornton, Charles A. Austin, Christopher P. TI Two high-throughput screening assays for aberrant RNA-protein interactions in myotonic dystrophy type 1 SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Myotonic dystrophy type 1; DM1; Muscleblind-like 1; MBNL1 ID TRINUCLEOTIDE REPEATS; SKELETAL-MUSCLE; RATIONAL DESIGN; CTG REPEAT; MBNL; BINDING; TRANSCRIPTS; MOLECULES; DISCOVERY; EXPANSION AB Myotonic dystrophy type 1 (DM1), the most prevalent form of adult muscular dystrophy, is caused by expansion of a CTG repeat in the 3' untranslated region of the DM protein kinase (DMPK) gene. The pathogenic effects of the CTG expansion arise from the deleterious effects of the mutant transcript. RNA with expanded CUG tracts alters the activities of several RNA binding proteins, including muscleblind-like 1 (MBNL1). MBNL1 becomes sequestered in nuclear foci in complex with the expanded CUG-repeat RNA. The resulting loss of MBNL1 activity causes misregulated alternative splicing of multiple genes, leading to symptoms of DM1. The binding interaction between MBNL1 and mutant RNA could be a key step in the pathogenesis of DM1 and serves as a potential target for therapeutic intervention. We have developed two high-throughput screens suitable assays using both homogenous time-resolved fluorescence energy transfer and AlphaScreen technologies to detect the binding of a C-terminally His-tagged MBNL1 and a biotinylated (CUG)(12) RNA. These assays are homogenous and successfully miniaturized to 1,536-well plate format. Both assays were validated and show robust signal-to-basal ratios and Z' factors. C1 [Chen, Catherine Z.; Southall, Noel; Marugan, Juan J.; Zheng, Wei; Austin, Christopher P.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Sobczak, Krzysztof; Hoskins, Jason; Thornton, Charles A.] Univ Rochester, Dept Neurol, Sch Med & Dent, Rochester, NY 14642 USA. [Sobczak, Krzysztof] Adam Mickiewicz Univ Poznan, Dept Gene Express, Inst Mol Biol & Biotechnol, PL-61251 Poznan, Poland. RP Zheng, W (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, 9800 Med Ctr Dr, Bethesda, MD 20892 USA. EM wzheng@mail.nih.gov; cthorn@mail.neurology.rochester.edu RI Hoskins, Jason/F-5672-2012; Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014 OI Hoskins, Jason/0000-0001-6944-1996; Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757 FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research, National Institutes of Health; Marigold Foundation; Polish Ministry of Science and Higher Education [N302 260938]; [MH087421]; [AR049077]; [NS48843] FX This research was supported by the Molecular Libraries Initiative of the NIH Roadmap for Medical Research, National Institutes of Health, the Marigold Foundation research fellowship, the US grants MH087421, AR049077, and NS48843, and the Polish Ministry of Science and Higher Education grant N302 260938. NR 32 TC 11 Z9 11 U1 1 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD FEB PY 2012 VL 402 IS 5 BP 1889 EP 1898 DI 10.1007/s00216-011-5604-0 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 886GA UT WOS:000299840700015 PM 22218462 ER PT J AU Lucenteforte, E La Vecchia, C Silverman, D Petersen, GM Bracci, PM Ji, BT Bosetti, C Li, D Gallinger, S Miller, AB Bueno-de-Mesquita, HB Talamini, R Polesel, J Ghadirian, P Baghurst, PA Zatonski, W Fontham, E Bamlet, WR Holly, EA Gao, YT Negri, E Hassan, M Cotterchio, M Su, J Maisonneuve, P Boffetta, P Duell, EJ AF Lucenteforte, E. La Vecchia, C. Silverman, D. Petersen, G. M. Bracci, P. M. Ji, B. T. Bosetti, C. Li, D. Gallinger, S. Miller, A. B. Bueno-de-Mesquita, H. B. Talamini, R. Polesel, J. Ghadirian, P. Baghurst, P. A. Zatonski, W. Fontham, E. Bamlet, W. R. Holly, E. A. Gao, Y. T. Negri, E. Hassan, M. Cotterchio, M. Su, J. Maisonneuve, P. Boffetta, P. Duell, E. J. TI Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4) SO ANNALS OF ONCOLOGY LA English DT Article DE alcohol drinking; case-control studies; ethanol; pancreatic cancer; pooled analysis; risk factors ID RISK-FACTORS; CIGARETTE-SMOKING; BEVERAGE CONSUMPTION; COFFEE CONSUMPTION; LIFE-STYLE; DIABETES-MELLITUS; EXOCRINE PANCREAS; MEDICAL HISTORY; TOBACCO; COHORT AB Background: Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. Methods: To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11 827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. Results: Compared with abstainers and occasional drinkers (<1 drink per day), we observed no association for light-to-moderate alcohol consumption (<= 4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2-2.2 for subjects drinking >= 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. Conclusion: This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer. C1 [Boffetta, P.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA. [Lucenteforte, E.; La Vecchia, C.; Bosetti, C.; Negri, E.] Ist Ric Farmacol Mario Negri, Dept Epidemiol, Milan, Italy. [Lucenteforte, E.; La Vecchia, C.] Univ Milan, Dept Occupat Hlth, Milan, Italy. [Silverman, D.; Ji, B. T.; Su, J.] NCI, Bethesda, MD 20892 USA. [Petersen, G. M.; Bamlet, W. R.] Mayo Clin, Rochester, MN USA. [Bracci, P. M.; Holly, E. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Li, D.; Hassan, M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gallinger, S.] Toronto Gen Hosp, Toronto, ON, Canada. [Miller, A. B.; Cotterchio, M.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Bueno-de-Mesquita, H. B.] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Bueno-de-Mesquita, H. B.] Univ Med Ctr Utrecht UMCU, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Talamini, R.; Polesel, J.] Ctr Riferimento Oncol CRO Natl Canc Inst, Aviano, PN, Italy. [Ghadirian, P.] Univ Montreal Hosp Ctr CRCHUM, Epidemiol Res Unit, Res Ctr, Montreal, PQ, Canada. [Baghurst, P. A.] Womens & Childrens Hosp, Adelaide, SA, Australia. [Zatonski, W.] Ctr Canc, Warsaw, Poland. [Zatonski, W.] Inst Oncol, Warsaw, Poland. [Fontham, E.] Louisiana State Univ, New Orleans, LA USA. [Gao, Y. T.] Shanghai Canc Inst, Shanghai, Peoples R China. [Cotterchio, M.] Canc Care Ontario, Populat Studies & Surveillance, Toronto, ON, Canada. [Maisonneuve, P.] European Inst Oncol, Milan, Italy. [Boffetta, P.] Int Prevent Res Inst, Lyon, France. [Duell, E. J.] Int Agcy Res Canc, F-69372 Lyon, France. [Duell, E. J.] Catalan Inst Oncol ICO IDIBELL, Barcelona, Spain. RP Boffetta, P (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM paolo.boffetta@exchange.mssm.edu RI Negri, Eva/B-7244-2013; Gallinger, Steven/E-4575-2013; OI Negri, Eva/0000-0001-9712-8526; Polesel, Jerry/0000-0001-9381-1520; Duell, Eric J/0000-0001-5256-0163; La Vecchia, Carlo/0000-0003-1441-897X; Lucenteforte, Ersilia/0000-0001-5608-5902; Maisonneuve, Patrick/0000-0002-5309-4704 FU Italian Association for Cancer Research; Louisiana Board of Regents Millennium Trust; National Institute of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics [N01-CP-51090, N01-CP-51089, N01-CP-51092, N01-CP-05225, N01-CP-31022, N01-CP-05227]; Cancer Research Society; National Cancer Institute of Canada; Dutch Ministry of Public Health, Welfare and Sports; National Cancer Institute [CA098889, CA59706, CA108370, CA109767, CA89726, N01-PC-35136]; Rombauer Pancreatic Cancer Research Fund; California Department of Public Health; Environmental Cancer Risk, Nutrition and Individual Susceptibility; Province of Milan; ISCIII of the Spanish Ministry of Health [RETICC DR06/0020] FX The Italian and Milan studies were supported by the Italian Association for Cancer Research. The Louisiana State University study was supported by the Louisiana Board of Regents Millennium Trust Health Excellence Fund [Project 5: HEF (2000-05, Genetics Studies in the Acadian Population)]. The NCI study was supported by the Intramural Research Program of the National Institute of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics (N01-CP-51090, N01-CP-51089, N01-CP-51092, N01-CP-05225, N01-CP-31022, N01-CP-05227). The Montreal investigation in the SEARCH study was supported by the Cancer Research Society, the Toronto contribution was supported by the National Cancer Institute of Canada, and the Netherlands investigation was supported by the Dutch Ministry of Public Health, Welfare and Sports (formerly Welfare, Health, and Culture). The University of California-San Francisco (UCSF) study work was supported in part by National Cancer Institute grants (CA098889 to E.J.D., CA59706, CA108370, CA109767, CA89726 to E.A.H.), and by the Rombauer Pancreatic Cancer Research Fund. Cancer incidence data collection in the UCSF study was supported by the California Department of Public Health, the National Cancer Institute's Surveillance, Epidemiology and End Results Program contract N01-PC-35136 awarded to the Northern California Cancer Center. E.L. was supported by Environmental Cancer Risk, Nutrition and Individual Susceptibility [European Union, Sixth Framework Program (FP6) Network of Excellence] and the Province of Milan. At Catalan Institute of Oncology, E.J.D. was supported by ISCIII of the Spanish Ministry of Health (RETICC DR06/0020). NR 79 TC 62 Z9 65 U1 0 U2 19 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 374 EP U353 DI 10.1093/annonc/mdr120 PG 9 WC Oncology SC Oncology GA 884YI UT WOS:000299744400015 PM 21536662 ER PT J AU Coudert, B Ciuleanu, T Park, K Wu, YL Giaccone, G Brugger, W Gopalakrishna, P Cappuzzo, F AF Coudert, B. Ciuleanu, T. Park, K. Wu, Y. -L. Giaccone, G. Brugger, W. Gopalakrishna, P. Cappuzzo, F. CA SATURN Investigators TI Survival benefit with erlotinib maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC) according to response to first-line chemotherapy SO ANNALS OF ONCOLOGY LA English DT Article DE erlotinib; maintenance; NSCLC; phase III; SATURN; stable disease ID GROWTH-FACTOR RECEPTOR; PHASE-III TRIAL; CISPLATIN PLUS GEMCITABINE; ENHANCED SENSITIVITY; CARBOPLATIN; PACLITAXEL; BEVACIZUMAB; DOCETAXEL; INSTITUTE; SELECTION AB Background: In the placebo-controlled phase III SATURN study, maintenance erlotinib after first-line chemotherapy demonstrated significantly prolonged progression-free survival (PFS) and overall survival (OS) in the overall study population of patients with advanced non-small-cell lung cancer (NSCLC). Methods: After four cycles of platinum-based doublet chemotherapy, patients without progressive disease (PD) were randomised to erlotinib (150 mg/day) or placebo until PD or unacceptable toxicity. In this pre-planned analysis, data are assessed according to response to first-line chemotherapy (complete/partial response [CR/PR] or stable disease [SD]). Results: Following first-line chemotherapy, 889 non-PD patients were included in the intention-to-treat population (55% SD; 44% CR/PR; < 1% unknown response). Erlotinib maintenance therapy significantly prolonged PFS in both the SD (hazard ratio [HR] = 0.68; P < 0.0001) and CR/PR (HR = 0.74; P = 0.0059) groups, while OS was significantly prolonged in the SD group only (HR = 0.72; P = 0.0019). The erlotinib-related OS benefit in the SD group remained significant across subgroups, irrespective of tumour histology and/or EGFR mutation status. The incidence of adverse events was similar in the SD group and the overall population, and erlotinib treatment did not negatively impact quality of life. Conclusions: Patients with advanced NSCLC and SD following first-line platinum-based doublet chemotherapy derive a significant OS benefit from maintenance erlotinib therapy. C1 [Coudert, B.] Ctr Georges Francois Leclerc, Dept Med Oncol, Off Clin & Therapeut Studies, F-21000 Dijon, France. [Ciuleanu, T.] Inst Oncol Ion Chiricuta, Cluj Napoca, Romania. [Park, K.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med, Seoul, South Korea. [Wu, Y. -L.] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China. [Giaccone, G.] NIH, Med Oncol Branch, Bethesda, MD 20892 USA. [Brugger, W.] Univ Freiburg, Dept Hematol Oncol, Schwarzwald Baar Clin, Teaching Hosp, Villingen Schwenningen, Germany. [Gopalakrishna, P.] Roche Prod Ltd, Dept Pharma Dev, Welwyn Garden City AL7 3AY, Herts, England. [Cappuzzo, F.] Osped Civile Livorno, Dept Hematol Oncol, Livorno, Italy. RP Coudert, B (reprint author), Ctr Georges Francois Leclerc, Dept Med Oncol, Off Clin & Therapeut Studies, 1 Rue Pr Marion, F-21000 Dijon, France. EM BCoudert@cgfl.fr RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Wu, Yi-Long/0000-0002-3611-0258; Cappuzzo, Federico/0000-0002-6295-6767 FU F. Hoffmann-La Roche Ltd. FX funding; This work was supported by F. Hoffmann-La Roche Ltd. NR 28 TC 49 Z9 53 U1 1 U2 8 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 388 EP 394 DI 10.1093/annonc/mdr125 PG 7 WC Oncology SC Oncology GA 884YI UT WOS:000299744400017 PM 21610154 ER PT J AU Le, K Li, RF Xu, SW Wu, XQ Huang, HQ Bao, YX Cai, Y Lan, T Moss, J Li, CX Zou, J Shen, XY Liu, PQ AF Le, Kang Li, Ruifang Xu, Suowen Wu, Xiaoqian Huang, Heqing Bao, Yingxia Cai, Yi Lan, Tian Moss, Joel Li, Cuixian Zou, Jian Shen, Xiaoyan Liu, Peiqing TI PPAR alpha activation inhibits endothelin-1-induced cardiomyocyte hypertrophy by prevention of NFATc4 binding to GATA-4 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE NFATc4; PPAR alpha; Cardiac hypertrophy; GATA-4; Fenofibrate ID CONGESTIVE-HEART-FAILURE; CARDIAC GENE-EXPRESSION; RECEPTOR-ALPHA; SIGNALING PATHWAYS; NUCLEAR-FACTOR; TRANSCRIPTION FACTORS; CELL HYPERTROPHY; NEONATAL-RAT; IN-VITRO; T-CELLS AB Peroxisome proliferator-activated receptor alpha (PPAR alpha) has been implicated in the pathogenesis of cardiac hypertrophy, although its mechanism of action remains largely unknown. To determine the effect of PPARa activation on endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy and explore its molecular mechanisms, we evaluated the interaction of PPAR alpha with nuclear factor of activated T-cells c4 (NFATc4) in nuclei of cardiomyocytes from neonatal rats in primary culture. In ET-1-stimulated cardiomyocytes, data from electrophoretic mobility-shift assays (EMSA) and co-immunoprecipitation (co-IP) revealed that fenofibrate (Fen), a PPAR alpha activator, in a concentration-dependent manner, enhanced the association of NFATc4 with PPAR alpha and decreased its interaction with GATA-4, in promoter complexes involved in activation of the rat brain natriuretic peptide (rBNP) gene. Effects of PPAR alpha overexpression were similar to those of its activation by Fen. PPAR alpha depletion by small interfering RNA abolished inhibitory effects of Fen on NFATc4 binding to GATA-4 and the rBNP DNA. Quantitative RT-PCR and confocal microscopy confirmed inhibitory effects of PPAR alpha activation on elevation of rBNP mRNA levels and ET-1-induced cardiomyocyte hypertrophy. Our results suggest that activated PPAR alpha can compete with GATA-4 binding to NFATc4, thereby decreasing transactivation of NFATc4, and interfering with ET-1 induced cardiomyocyte hypertrophy. (C) 2011 Elsevier Inc. All rights reserved. C1 [Shen, Xiaoyan] Sun Yat Sen Univ, Dept Pharmacol & Toxicol, Sch Pharmaceut Sci, Higher Educ Mega Ctr, Guangzhou 510006, Guangdong, Peoples R China. [Li, Ruifang] Henan Univ Sci & Technol, Dept Pharmacol, Luoyang, Peoples R China. [Wu, Xiaoqian] Guangzhou Med Univ, Dept Pharmacol, Guangzhou, Guangdong, Peoples R China. [Le, Kang; Xu, Suowen; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Shen, XY (reprint author), Sun Yat Sen Univ, Dept Pharmacol & Toxicol, Sch Pharmaceut Sci, Higher Educ Mega Ctr, 132 E Wai Huan Rd, Guangzhou 510006, Guangdong, Peoples R China. EM xyshen08@gmail.com; liupq@mail.sysu.edu.cn RI Le, Kang/D-1630-2016 FU National Natural Science Foundation of China [81072641]; NSFC-CIHR China-Canada Joint Health Research Initiative Proposal [30811120434]; National Science and Technology Major Project of China "Key New Drug Creation and Manufacturing Program" [2009ZX09102-152, 2011ZX09401-307]; Major Project of Guangdong Province [2008A030201013]; Major Project of Guangzhou City [2008Z1-E571]; National Institutes of Health, NHLBI FX This work was supported by grants from the National Natural Science Foundation of China (No. 81072641); NSFC-CIHR China-Canada Joint Health Research Initiative Proposal (No. 30811120434); the National Science and Technology Major Project of China "Key New Drug Creation and Manufacturing Program" (No. 2009ZX09102-152, 2011ZX09401-307); Major Project of Guangdong Province (2008A030201013) Major Project of Guangzhou City (2008Z1-E571), and Intramural Research Program, National Institutes of Health, NHLBI (J.M.). We thank Dr. Martha Vaughan (Cardiovascular and Pulmonary Branch, NHLBI, National Institutes of Health) for valuable discussions and manuscript review. We extend our gratitude to all members of the Department of Pharmacology and Toxicology for technical assistance. NR 49 TC 15 Z9 17 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD FEB 1 PY 2012 VL 518 IS 1 BP 71 EP 78 DI 10.1016/j.abb.2011.11.024 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 885TM UT WOS:000299803700010 PM 22198280 ER PT J AU Smith, SB Maixner, DW Fillingim, RB Slade, G Gracely, RH Ambrose, K Zaykin, DV Hyde, C John, S Tan, K Maixner, W Diatchenko, L AF Smith, Shad B. Maixner, Dylan W. Fillingim, Roger B. Slade, Gary Gracely, Richard H. Ambrose, Kirsten Zaykin, Dmitri V. Hyde, Craig John, Sally Tan, Keith Maixner, William Diatchenko, Luda TI Large candidate gene association study reveals genetic risk factors and therapeutic targets for fibromyalgia SO ARTHRITIS AND RHEUMATISM LA English DT Article ID O-METHYLTRANSFERASE GENE; IRRITABLE-BOWEL-SYNDROME; RGS PROTEINS; PAIN; POLYMORPHISM; RECEPTOR; TRANSPORTER; EXPRESSION; RAT; THRESHOLDS AB Objective Fibromyalgia (FM) represents a complex disorder that is characterized by widespread pain and tenderness and is frequently accompanied by additional somatic and cognitive/affective symptoms. Genetic risk factors are known to contribute to the etiology of the syndrome. The aim of this study was to examine >350 genes for association with FM, using a large-scale candidate gene approach. Methods. The study group comprised 496 patients with FM (cases) and 348 individuals with no chronic pain (controls). Genotyping was performed using a dedicated gene array chip, the Pain Research Panel, which assays variants characterizing >350 genes known to be involved in the biologic pathways relevant to nociception, inflammation, and mood. Association testing was performed using logistic regression. Results. Significant differences in allele frequencies between cases and controls were observed for 3 genes: GABRB3 (rs4906902; P = 3.65 x 10(-6)), TAAR1 (rs8192619; P = 1.11 x 10(-5)), and GBP1 (rs7911; P = 1.06 x 10(-4)). These 3 genes and 7 other genes with suggestive evidence for association were examined in a second, independent cohort of patients with FM and control subjects who were genotyped using the Perlegen 600K platform. Evidence of association in the replication cohort was observed for TAAR1, RGS4, CNR1, and GRIA4. Conclusion. Variation in these 4 replicated genes may serve as a basis for development of new diagnostic approaches, and the products of these genes may contribute to the pathophysiology of FM and represent potential targets for therapeutic action. C1 [Smith, Shad B.; Fillingim, Roger B.; Slade, Gary; Gracely, Richard H.; Ambrose, Kirsten; Maixner, William; Diatchenko, Luda] Algynomics, Chapel Hill, NC 27514 USA. [Smith, Shad B.; Maixner, Dylan W.; Slade, Gary; Gracely, Richard H.; Maixner, William; Diatchenko, Luda] Univ N Carolina, Chapel Hill, NC USA. [Fillingim, Roger B.] Univ Florida, Gainesville, FL USA. [Zaykin, Dmitri V.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. [Hyde, Craig; John, Sally] Pfizer Global Res & Dev, Groton, CT USA. [Tan, Keith] Pfizer Global Res & Dev, Sandwich, Kent, England. RP Diatchenko, L (reprint author), Algynomics, 208 N Columbia St, Chapel Hill, NC 27514 USA. EM ldiatchenko@algynomics.com FU Pfizer; Algynomics; NIH (National Institute of Environmental Health Sciences); NIH [R01-DE-16558]; Cytogel; Codman; Eli Lilly; Jazz Pharmaceuticals FX Supported by Pfizer and Algynomics. Dr. Zaykin's work was supported by the NIH Intramural Research Program (National Institute of Environmental Health Sciences). An NIH grant (National Institute of Dental and Craniofacial Research grant R01-DE-16558 to Drs. Maixner and Diatchenko) supported the collection of a portion of the study data.; Dr. Fillingim has received consulting fees, speaking fees, and/or honoraria from Cytogel and Codman (less than $10,000 each). Dr. Gracely has received consulting fees, speaking fees, and/or honoraria from Eli Lilly and Jazz Pharmaceuticals (less than $10,000 each). Mr. Maixner has received consulting fees, speaking fees, and/or honoraria from Algynomics (less than $10,000). Dr. Diatchenko has received consulting fees, speaking fees, and/or honoraria from Algynomics (more than $10,000) and has provided paid consultation with investment analysts on behalf of Algynomics. Mr. Maixner and Dr. Diatchenko are coinventors on the patent for the Pain Research Panel, a dedicated gene array chip used for genotyping; the patent is owned by the University of North Carolina and licensed to Algynomics. Drs. Smith, Fillingim, Slade, Gracely, and Diatchenko, and Mr. Maixner and Ms Ambrose own stock or stock options in Algynomics; Mr. Maixner is an equity holder in Algynomics. Drs. Hyde, John, and Tan own stock or stock options in Pfizer. NR 51 TC 28 Z9 30 U1 0 U2 11 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 584 EP 593 DI 10.1002/art.33338 PG 10 WC Rheumatology SC Rheumatology GA 883HU UT WOS:000299625700034 PM 21905019 ER PT J AU Abidi, MH Agarwal, R Tageja, N Ayash, L Ventimiglia, M Deol, A Al-Kadhimi, Z Lum, L Ratanatharathorn, V Abrams, J Uberti, JP AF Abidi, M. H. Agarwal, R. Tageja, N. Ayash, L. Ventimiglia, M. Deol, A. Al-Kadhimi, Z. Lum, L. Ratanatharathorn, V Abrams, J. Uberti, J. P. TI MELPHALAN 180mg/m(2) CAN BE SAFELY ADMINISTERED AS CONDITIONING REGIMEN PRIOR TO AN AUTOLOGOUS STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA PATIENTS WITH CREATININE CLEARANCE <= 60ml/min/1.73 m(2) WITH USE OF PALIFERMIN FOR CYTO-PROTECTION: RESULTS OF A PHASE I TRIAL 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 [Abidi, M. H.; Ayash, L.; Deol, A.; Al-Kadhimi, Z.; Lum, L.; Ratanatharathorn, V; Abrams, J.; Uberti, J. P.] Wayne State Univ, Detroit, MI USA. [Abidi, M. H.; Ayash, L.; Ventimiglia, M.; Deol, A.; Al-Kadhimi, Z.; Lum, L.; Ratanatharathorn, V; Abrams, J.; Uberti, J. P.] Karmanos Canc Ctr, Detroit, MI USA. [Agarwal, R.] Cent Michigan Univ, Saginaw, MI USA. [Tageja, N.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 130 BP S252 EP S253 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600131 ER PT J AU Baird, K Booher, S Comis, LE Joe, GO Steinberg, SM Spencer, SD Figg, WD Takebe, N Pavletic, SZ Cowen, EW AF Baird, K. Booher, S. Comis, L. E. Joe, G. O. Steinberg, S. M. Spencer, S. D. Figg, W. D. Takebe, N. Pavletic, S. Z. Cowen, E. W. TI PHASE II PILOT STUDY OF IMATINIB MESYLATE FOR THE TREATMENT OF SEVERE SCLEROTIC SKIN CHRONIC GRAFT VERSUS HOST DISEASE (ScGVHD) 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 [Baird, K.; Booher, S.; Comis, L. E.; Joe, G. O.; Steinberg, S. M.; Spencer, S. D.; Figg, W. D.; Takebe, N.; Pavletic, S. Z.; Cowen, E. W.] NIH, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 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 16 BP S208 EP S208 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600017 ER PT J AU Battiwalla, M Fakhrejahani, F Klotz, J Pophali, P Draper, D Haggerty, J McIver, Z Chawla, K Ito, S Barrett, J AF Battiwalla, M. Fakhrejahani, F. Klotz, J. Pophali, P. Draper, D. Haggerty, J. McIver, Z. Chawla, K. Ito, S. Barrett, J. TI RADIATION EXPOSURE FROM DIAGNOSTIC PROCEDURES IN ALLOGENEIC STEM CELL TRANSPLANTATION DOES NOT SIGNIFICANTLY IMPACT OVERALL SURVIVAL OR NON-RELAPSE MORTALITY 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 [Battiwalla, M.; Fakhrejahani, F.; Klotz, J.; Pophali, P.; Draper, D.; Haggerty, J.; McIver, Z.; Chawla, K.; Ito, S.; Barrett, J.] NHLBI, NIH, Bethesda, MD 20892 USA. RI Pophali, Priyanka/P-8646-2016 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 370 BP S341 EP S341 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600369 ER PT J AU Battiwalla, M McIver, Z Klotz, J Draper, D Haggerty, J Chawla, K Superata, J Stroncek, D Khuu, H Citrin, D Sabatino, M Leitman, S Ito, S Barrett, J AF Battiwalla, M. McIver, Z. Klotz, J. Draper, D. Haggerty, J. Chawla, K. Superata, J. Stroncek, D. Khuu, H. Citrin, D. Sabatino, M. Leitman, S. Ito, S. Barrett, J. TI OUTCOMES AFTER CD34+SELECTION WITH OR WITHOUT THE ADDITION OF PHOTO-ALLODEPLETED T LYMPHOCYTES IN MYELOABLATIVE HLA-MATCHED SIBLING 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 [Battiwalla, M.; McIver, Z.; Klotz, J.; Draper, D.; Haggerty, J.; Chawla, K.; Superata, J.; Ito, S.; Barrett, J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Stroncek, D.; Khuu, H.; Sabatino, M.; Leitman, S.] NIH, CC, Bethesda, MD 20892 USA. [Citrin, D.] NCI, CCR, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 151 BP S260 EP S260 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600152 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 Buxbaum, NP Williams, KM Amarnath, S Treadwell, S Eckhaus, M Gress, RE AF Buxbaum, N. P. Williams, K. M. Amarnath, S. Treadwell, S. Eckhaus, M. Gress, R. E. TI SEVERE CHRONIC GRAFT-VERSUS-HOST DISEASE IS ASSOCIATED WITH IMPAIRED THYMOPOIESIS AND PERIPHERAL LYMPHOCYTE EXPANSION 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 [Buxbaum, N. P.; Williams, K. M.; Amarnath, S.; Treadwell, S.; Eckhaus, M.; Gress, R. E.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 435 BP S364 EP S365 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600434 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 Cruz, CRY Micklethwaite, KP Savoldo, B Ku, S Krance, RA Diouf, O Kamble, R Kennedy-Nasser, A Barrett, AJ Shpall, EJ Heslop, HE Rooney, CM Brenner, MK Bollard, CM Dotti, G AF Cruz, C. R. Y. Micklethwaite, K. P. Savoldo, B. Ku, S. Krance, R. A. Diouf, O. Kamble, R. Kennedy-Nasser, A. Barrett, A. J. Shpall, E. J. Heslop, H. E. Rooney, C. M. Brenner, M. K. Bollard, C. M. Dotti, G. TI SAFETY AND PERSISTENCE OF INFUSED CD19-CAR-MODIFIED MULTIVIRUS SPECIFIC CTLS IN B CELL MALIGNANCIES POST ALLOGENEIC 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 [Cruz, C. R. Y.; Micklethwaite, K. P.; Savoldo, B.; Ku, S.; Krance, R. A.; Diouf, O.; Kamble, R.; Kennedy-Nasser, A.; Heslop, H. E.; Rooney, C. M.; Brenner, M. K.; Bollard, C. M.; Dotti, G.] Texas Childrens Hosp, Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. [Barrett, A. J.] NIH, Bethesda, MD 20892 USA. [Shpall, E. J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 191 BP S274 EP S274 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600192 ER PT J AU Kennedy-Nasser, AA Ku, S Melenhorst, J Barrett, J Hazrat, Y Durett, AG Foster, A Savoldo, B Yvon, E Heslop, HE Carrum, G Kamble, RT Brenner, MK Krance, RA Bollard, CM AF Kennedy-Nasser, A. A. Ku, S. Melenhorst, J. Barrett, J. Hazrat, Y. Durett, A. G. Foster, A. Savoldo, B. Yvon, E. Heslop, H. E. Carrum, G. Kamble, R. T. Brenner, M. K. Krance, R. A. Bollard, C. M. TI ULTRA LOW-DOSE IL-2 MEDIATED EXPANSION OF REGULATORY T CELLS AS GVHD PROPHYLAXIS FOR RECIPIENTS OF ALLOGENEIC HEMATOPOIETIC STEM CELLS 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 [Kennedy-Nasser, A. A.; Ku, S.; Hazrat, Y.; Durett, A. G.; Foster, A.; Savoldo, B.; Yvon, E.; Heslop, H. E.; Carrum, G.; Kamble, R. T.; Brenner, M. K.; Krance, R. A.; Bollard, C. M.] Baylor Coll Med, Houston, TX 77030 USA. [Melenhorst, J.; Barrett, J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 416 BP S358 EP S358 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600415 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 Pophali, PA Klotz, J Chawla, K Koklanaris, E Ito, S Le, RQ Savani, BN Barrett, J Battiwalla, M AF Pophali, P. A. Klotz, J. Chawla, K. Koklanaris, E. Ito, S. Le, R. Q. Savani, B. N. Barrett, J. Battiwalla, M. TI MAGNITUDE OF DYSLIPIDEMIAS AND CARDIOVASCULAR RISK IN SURVIVORS OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (SCT) UP TO THE SECOND DECADE POST-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 [Pophali, P. A.; Klotz, J.; Chawla, K.; Koklanaris, E.; Ito, S.; Le, R. Q.; Barrett, J.; Battiwalla, M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Savani, B. N.] Vanderbilt Univ, Nashville, TN USA. RI Pophali, Priyanka/P-8646-2016 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 222 BP S286 EP S286 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600223 ER PT J AU Pophali, PA Klotz, J Koklanaris, E Savani, BN Chawla, K Le, RQ Wu, C Barrett, J Battiwalla, M AF Pophali, P. A. Klotz, J. Koklanaris, E. Savani, B. N. Chawla, K. Le, R. Q. Wu, C. Barrett, J. Battiwalla, M. TI CHRONIC GVHD AND AGE ARE NOT ASSOCIATED WITH BONE MINERAL DENSITY LOSS IN THE SECOND DECADE POST-ALLOGENEIC 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 [Pophali, P. A.; Klotz, J.; Koklanaris, E.; Chawla, K.; Le, R. Q.; Wu, C.; Barrett, J.; Battiwalla, M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Savani, B. N.] Vanderbilt Univ, Nashville, TN USA. RI Pophali, Priyanka/P-8646-2016 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 200 BP S277 EP S277 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600201 ER PT J AU Shah, NN Loeb, D Khuu, H Stroncek, D Raffeld, M Delbrook, C Richards, K Baird, K Levine, J Leitman, S Mackall, CL Fry, TJ Wayne, AS AF Shah, N. N. Loeb, D. Khuu, H. Stroncek, D. Raffeld, M. Delbrook, C. Richards, K. Baird, K. Levine, J. Leitman, S. Mackall, C. L. Fry, T. J. Wayne, A. S. TI A PILOT TRIAL OF WTI PEPTIDE-LOADED ALLOGENEIC DENDRITIC CELL (DC) VACCINATION AND DONOR LYMPHOCYTE INFUSION (DLI) FOR WTI-EXPRESSING HEMATOLOGIC MALIGNANCIES AND POST-TRANSPLANT RELAPSE 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.; Khuu, H.; Stroncek, D.; Raffeld, M.; Delbrook, C.; Richards, K.; Baird, K.; Levine, J.; Leitman, S.; Mackall, C. L.; Fry, T. J.; Wayne, A. S.] NIH, Bethesda, MD 20892 USA. [Loeb, D.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 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 150 BP S259 EP S260 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600151 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 Shand, JC Capitini, CM Qin, H Fry, TJ AF Shand, J. C. Capitini, C. M. Qin, H. Fry, T. J. TI BROAD EXPRESSION OF A MINOR HISTOCOMPATIBILITY ANTIGEN RESULTS IN IMPAIRED ANTITUMOR IMMUNITY THAT CANNOT BE OVERCOME WITH DENDRITIC CELL VACCINATION 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 [Shand, J. C.] Johns Hopkins Univ, Natl Canc Inst Combined Fellowship, Baltimore, MD USA. [Capitini, C. M.; Qin, H.; Fry, T. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 334 BP S328 EP S328 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600333 ER PT J AU Shanis, DL Pophali, P Koklanaris, E Battiwalla, M Barrett, J Stratton, P AF Shanis, D. L. Pophali, P. Koklanaris, E. Battiwalla, M. Barrett, J. Stratton, P. TI CERVICAL CYTOLOGY SCREENING IN LONG-TERM SURVIVORS OF ALLOGENEIC STEM CELL TRANSPLANTATION WITH GENITAL 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 [Shanis, D. L.; Stratton, P.] Eunice Kennedy Shriver NICHD, NIH, Bethesda, MD USA. [Pophali, P.; Koklanaris, E.; Battiwalla, M.; Barrett, J.] NHLBI, NIH, Bethesda, MD 20892 USA. RI Pophali, Priyanka/P-8646-2016 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 214 BP S282 EP S282 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600215 ER PT J AU Shanis, DL Pophali, P Koklanaris, E Savani, BN Battiwalla, M Barrett, J Stratton, P AF Shanis, D. L. Pophali, P. Koklanaris, E. Savani, B. N. Battiwalla, M. Barrett, J. Stratton, P. TI HIGH RATES OF GENITAL TRACT DYSPLASIA IN LONG-TERM SURVIVORS OF ALLOGENEIC STEM CELL TRANSPLANTATION AND ASSOCIATED RISK FACTORS 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 [Shanis, D. L.; Stratton, P.] Eunice Kennedy Shriver NICHD, NIH, Bethesda, MD USA. [Pophali, P.; Koklanaris, E.; Battiwalla, M.; Barrett, J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Savani, B. N.] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RI Pophali, Priyanka/P-8646-2016 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 212 BP S282 EP S282 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600213 ER PT J AU Tomblyn, M Trifilio, S Chen, M Klein, J Boeckh, M Gea-Banacloche, J Szabolcs, P Bennett, C AF Tomblyn, M. Trifilio, S. Chen, M. Klein, J. Boeckh, M. Gea-Banacloche, J. Szabolcs, P. Bennett, C. TI RISK FACTORS AND OUTCOMES IN PATIENTS WITH ATYPICAL MOLD INFECTION (AMI) FOLLOWING ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (HCT): A CIBMTR ANALYSIS FROM THE INFECTION AND IMMUNE RECONSTITUTION WORKING COMMITTEE 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 [Tomblyn, M.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Trifilio, S.] Northwestern Univ, Chicago, IL 60611 USA. [Chen, M.; Klein, J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Boeckh, M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Gea-Banacloche, J.] NIH, Bethesda, MD 20892 USA. [Szabolcs, P.] Univ Pittsburgh, Pittsburgh, PA USA. [Bennett, C.] Univ S Carolina, Columbia, SC 29208 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2012 VL 18 IS 2 SU 2 MA 96 BP S238 EP S238 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600097 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 Williams, KM Pavletic, SZ Hakim, FT Mitchell, SA Gea-Banacloche, JC Comis, L Cowen, EW Baird, K Shelhamer, JH Blacklock-Schuver, BAJ Avila, D Carpenter, A Urban, A Taylor, T Zuchlinski, D Baruffaldi, J Lee, S Gress, RE AF Williams, K. M. Pavletic, S. Z. Hakim, F. T. Mitchell, S. A. Gea-Banacloche, J. C. Comis, L. Cowen, E. W. Baird, K. Shelhamer, J. H. Blacklock-Schuver, B. A. J. Avila, D. Carpenter, A. Urban, A. Taylor, T. Zuchlinski, D. Baruffaldi, J. Lee, S. Gress, R. E. TI PRELIMINARY RESULTS OF A PHASE II TRIAL OF MONTELUKAST FOR THE TREATMENT OF BRONCHIOLITIS OBLITERANS SYNDROME AFTER HSCT 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 [Williams, K. M.; Pavletic, S. Z.; Hakim, F. T.; Mitchell, S. A.; Gea-Banacloche, J. C.; Baird, K.; Blacklock-Schuver, B. A. J.; Avila, D.; Carpenter, A.; Urban, A.; Taylor, T.; Zuchlinski, D.; Baruffaldi, J.; Gress, R. E.] NCI, NIH, Bethesda, MD 20892 USA. [Lee, S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 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 428 BP S362 EP S362 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 880HQ UT WOS:000299398600427 ER PT J AU Scott, DW Lozier, JN AF Scott, David W. Lozier, Jay N. TI Gene therapy for haemophilia: prospects and challenges to prevent or reverse inhibitor formation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE haemophilia; factor VIII (FVIII); factor IX (FIX); gene therapy; immune tolerance ID HUMAN-FACTOR-VIII; REGULATORY T-CELLS; HEMATOPOIETIC STEM-CELLS; IMMUNE TOLERANCE INDUCTION; ANTIGEN-SPECIFIC EFFECTOR; A MICE; FACTOR-IX; IMMUNOLOGICAL-TOLERANCE; NEPHROTIC SYNDROME; TRANSGENE PRODUCT AB Monogenic hereditary diseases, such as haemophilia A and B, are ideal targets for gene therapeutic approaches. While these diseases can be treated with protein therapeutics, such as factor VIII (FVIII) or IX (FIX), the notion that permanent transfer of the genes encoding these factors can cure haemophilia is very attractive. An underlying problem with a gene therapy approach, however, is the patients immune response to the therapeutic protein (as well as to the transmission vector), leading to the formation of inhibitory antibodies. Even more daunting is reversing an existing immune response in patients with pre-existing inhibitors. In this review, we will describe the laboratory and clinical progress, and the challenges met thus far, in achieving the goal of gene therapy efficacy, with a focus on the goal of tolerance induction. C1 [Scott, David W.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. [Lozier, Jay N.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. RP Scott, DW (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM david.scott@usuhs.mil FU USPHS NIH [HL061883, AI035622, DK068343]; Haemophilia Association of New York FX The author is indebted to Drs. Federico Mingozzi (Children's Hospital of Philadelphia) and Roland Herzog (University of Florida) for their critical review and suggestions, and to Drs. Belinda Jackson and Aihong Zhang (USUHS), and Keith Hoots (NIH) for reading the manuscript. The author's work cited herein was supported by grants from the USPHS NIH (HL061883, AI035622, and DK068343 to DWS), as well as by funds from the Haemophilia Association of New York. The opinions expressed in this manuscript are those of the authors and do not constitute US government policy. This is a US government work and there are no restrictions on its use. (David W. Scott and Jay N. Lozier wrote the paper.) NR 87 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2012 VL 156 IS 3 BP 295 EP 302 DI 10.1111/j.1365-2141.2011.08925.x PG 8 WC Hematology SC Hematology GA 874UQ UT WOS:000298984000001 PM 22055221 ER PT J AU Mast, AE Lee, TH Schlumpf, KS Wright, DJ Johnson, B Carrick, DM Cable, RG Kiss, JE Glynn, SA Steele, WR Murphy, EL Sacher, R Busch, MP AF Mast, Alan E. Lee, Tzong-Hae Schlumpf, Karen S. Wright, David J. Johnson, Bryce Carrick, Danielle M. Cable, Ritchard G. Kiss, Joseph E. Glynn, Simone A. Steele, Whitney R. Murphy, Edward L. Sacher, Ronald Busch, Michael P. CA NHLBI Retrovirus Epidemiol Donor TI The impact of HFE mutations on haemoglobin and iron status in individuals experiencing repeated iron loss through blood donation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE HFE; blood donor; iron deficiency; haemoglobin; ferritin ID GENOME-WIDE ASSOCIATION; DONORS; DEFICIENCY; OVERLOAD; HEMOCHROMATOSIS; HEPCIDIN; TMPRSS6; GENE; METABOLISM; VARIANTS AB Frequent blood donors become iron deficient. HFE mutations are present in over 30% of donors. A 24-month study of 888 first time/reactivated donors and 1537 frequent donors measured haemoglobin and iron status to assess how HFE mutations impact the development of iron deficiency erythropoiesis. Donors with two HFE mutations had increased baseline haemoglobin and iron stores as did those with one mutation, albeit to a lesser extent. Over multiple donations haemoglobin and iron status of donors with HFE mutations paralleled those lacking mutations. The prevalence of HFE mutations was not increased in higher intensity donors. Thus, in general, HFE mutations do not temper donation-induced changes in haemoglobin and iron status. However, in Black donors there was an increase of H63D carriers at baseline, from 3.7% in first time/reactivated donors to 15.8% in frequent donors, suggesting that the relative effects of HFE mutations on iron absorption may vary between racial/ethnic groups. In secondary analyses, venous haemoglobin decreased more slowly in donors with ferritin =12 mu g/l; and haemoglobin recovery time was shorter in donors with reticulocyte haemoglobin (CHr) =32.6 pg, indicating that these biochemical measures are better indicators of a donors response to phlebotomy than their HFE mutation status. C1 [Mast, Alan E.] Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI 53201 USA. [Mast, Alan E.] Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA. [Lee, Tzong-Hae; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA. [Schlumpf, Karen S.; Wright, David J.; Johnson, Bryce; Carrick, Danielle M.; Steele, Whitney R.] Westat Corp, Rockville, MD USA. [Cable, Ritchard G.] Amer Red Cross Blood Serv, Farmington, CT USA. [Kiss, Joseph E.] Inst Transfus Med, Pittsburgh, PA USA. [Glynn, Simone A.] NHLBI, Bethesda, MD 20892 USA. [Murphy, Edward L.] Univ Calif San Francisco, San Francisco & Blood Syst Res Inst, San Francisco, CA 94143 USA. [Sacher, Ronald] Univ Cincinnati, Acad Hlth Ctr, Hoxworth Blood Ctr, Cincinnati, OH USA. RP Mast, AE (reprint author), Blood Ctr Wisconsin, Blood Res Inst, 8727 Watertown Plank Rd,POB 2178, Milwaukee, WI 53201 USA. EM alan.mast@bcw.edu FU NHLBI [N01-HB-47168, -47169, -47170, -47171, -47172, -47174, -47175, -57181] FX This work was supported by NHLBI contracts N01-HB-47168, -47169, -47170, -47171, -47172, -47174, -47175, and -57181. NR 23 TC 10 Z9 10 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2012 VL 156 IS 3 BP 388 EP 401 DI 10.1111/j.1365-2141.2011.08952.x PG 14 WC Hematology SC Hematology GA 874UQ UT WOS:000298984000012 PM 22118647 ER PT J AU Speranza, G Gutierrez, ME Kummar, S Strong, JM Parker, RJ Collins, J Yu, YK Cao, L Murgo, AJ Doroshow, JH Chen, A AF Speranza, Giovanna Gutierrez, Martin E. Kummar, Shivaani Strong, John M. Parker, Robert J. Collins, Jerry Yu, Yunkai Cao, Liang Murgo, Anthony J. Doroshow, James H. Chen, Alice TI Phase I study of the synthetic triterpenoid, 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid (CDDO), in advanced solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Triterpenoid; CDDO; Adverse event; Thromboembolism ID ACTIVATED RECEPTOR-GAMMA; ACUTE MYELOGENOUS LEUKEMIA; VENOUS THROMBOSIS; CANCER CELLS; APOPTOSIS; PATHWAY; GROWTH; AGGREGATION; TRAIL; FLIP AB The triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic Acid (CDDO, previously RTA 401) is a multifunctional molecule that controls cellular growth and differentiation. While CDDO is capable of activating the transcription factor peroxisome proliferator activator receptor-gamma (PPAR gamma), its apoptotic effects in malignant cells have been shown to occur independently of PPAR gamma. A phase I dose-escalation study was conducted to determine the toxicity, the maximum tolerated dose, and the pharmacokinetics and pharmacodynamics of CDDO, administered as a 5-day continuous infusion every 28 days in patients with advanced cancers. An accelerated titration design was followed, with one patient per cohort entered, and doses ranging from 0.6 to 38.4 mg/m(2)/h. Pharmacokinetics of CDDO was assessed and cleaved poly (ADP-ribose) polymerase (c-PARP), as a marker of apoptosis, was measured in peripheral blood mononuclear cells to assess drug effect. Seven patients, one patient per dose level up to dose level 7 (38.4 mg/m(2)/h), were enrolled and received a total of 11 courses of treatment. Cmax increased proportionally with dose. Preclinically determined efficacious blood level (1 mu M) of drug was attained at the highest dose level. One patient, at dose level 6, experienced grade 2 mucositis, nausea, vomiting, and anorexia. Four patients developed thromboembolic events subsequently considered as dose-limiting toxicity. No antitumor activity was noted. A causal relationship of observed thromboembolic events to CDDO was considered possible but could not be established. C1 [Speranza, Giovanna; Kummar, Shivaani; Collins, Jerry; Murgo, Anthony J.; Doroshow, James H.; Chen, Alice] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Gutierrez, Martin E.; Kummar, Shivaani; Yu, Yunkai; Cao, Liang; Doroshow, James H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Strong, John M.; Parker, Robert J.] Food & Drug Adm, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Silver Spring, MD USA. RP Chen, A (reprint author), 6301 Execut Blvd,Suite 7130, Rockville, MD 20852 USA. EM chenali@mail.nih.gov FU NCI NIH HHS [HHSN261200800001E] NR 33 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD FEB PY 2012 VL 69 IS 2 BP 431 EP 438 DI 10.1007/s00280-011-1712-y PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 881UW UT WOS:000299516700016 PM 21805353 ER PT J AU Nikanjam, M Chadwick, EG Robbins, B Alvero, C Palumbo, P Yogev, R Pinto, J Hazra, R Hughes, ML Heckman, BE Capparelli, EV AF Nikanjam, M. Chadwick, E. G. Robbins, B. Alvero, C. Palumbo, P. Yogev, R. Pinto, J. Hazra, R. Hughes, M. L. Heckman, B. E. Capparelli, E. V. CA IMPAACT P1030 Team TI Assessment of Lopinavir Pharmacokinetics With Respect to Developmental Changes in Infants and the Impact on Weight Band-Based Dosing SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID VIRUS-INFECTED CHILDREN; POPULATION PHARMACOKINETICS; HIV-1-INFECTED PATIENTS; PROTEASE INHIBITOR; RITONAVIR; HIV-1; AGE; LOPINAVIR/RITONAVIR; COMBINATION; NELFINAVIR AB Improved antiretroviral therapies are needed for the treatment of HIV-infected infants, given the rapid progression of the disease and drug resistance resulting from perinatal exposure to antiretrovirals. We examined longitudinal pharmacokinetics (PK) data from a clinical trial of lopinavir/ritonavir (LPV/r) in HIV-infected infants in whom therapy was initiated at less than 6 months of age. A population PK analysis was performed using NONMEM to characterize changes in lopinavir (LPV) PK relating to maturational changes in infants, and to assess dosing requirements in this population. We also investigated the relationship between LPV PK and viral dynamic response. Age and ritonavir concentrations were the only covariates found to be significant. Population PK of LPV was characterized by high apparent clearance (CL/F) in young infants, which decreased with increasing age. Although younger infants had lower LPV concentrations, the viral dynamics did not correlate with initial LPV exposure. Monte Carlo simulations demonstrated that WHO weight band based dosing recommendations predicted therapeutic LPV concentrations and provided drug exposure levels comparable to those resulting from US Food and Drug Administration (FDA)-suggested dosing regimens. C1 [Nikanjam, M.; Capparelli, E. V.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Chadwick, E. G.; Yogev, R.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Robbins, B.] Univ Nebraska, Med Ctr, Omaha, NE USA. [Alvero, C.; Hughes, M. L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Palumbo, P.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Pinto, J.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [Hazra, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Heckman, B. E.] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. RP Capparelli, EV (reprint author), Univ Calif San Diego, La Jolla, CA 92093 USA. EM ecapparelli@ucsd.edu FU National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; Statistical and Data Analysis Center at the Harvard School of Public Health under NIAID [5 U01 AI41110, 1 U01 AI068616]; NIAID; NICHD [N01-DK-9-001/HHSN267200800001C]; Roche; Abbott Labs; Boehringer Ingelheim; Bristol-Meyers Squibb; Chiron; Medicines Development; Pfizer; Tibotec; Vironyx FX The study team thanks John Rodman for his contributions to the design and performance of the study, Donald Barkauskas for his assistance with the model cross-validation, Abbott Laboratories for donating the study drug, and the patients and families who participated in this study. Overall support for the International Maternal-Pediatric-Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) (U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) (AI068632). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was supported by the Statistical and Data Analysis Center at the Harvard School of Public Health, under NIAID cooperative agreement 5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group and 1 U01 AI068616 with the IMPAACT Group. Support at the study sites was provided by NIAID and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract N01-DK-9-001/HHSN267200800001C).; E.V.C. has served as a consultant to GlaxoSmithKline, Bristol-Meyers Squibb, and Johnson & Johnson. E.G.C. has had consultancies with Pfizer and Bristol-Meyers Squibb and has owned stock+/-stock options in Abbott Labs, GlaxoSmithKline, Merck Inc., Bristol-Meyers Squibb, and Schering Plough. M.D.H. received grant support from Roche, and honoraria/consultancy fees from Abbott Labs, Boehringer Ingelheim, Bristol-Meyers Squibb, Chiron, Medicines Development, Roche, Pfizer, Tibotec, and Vironyx. R.Y. has served on speaker's bureaus for Merck Inc. and GlaxoSmithKline. The other authors declared no conflict of interest NR 29 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2012 VL 91 IS 2 BP 243 EP 249 DI 10.1038/clpt.2011.218 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 883SC UT WOS:000299654000023 PM 22190064 ER PT J AU Kaplan, RM AF Kaplan, Robert M. TI Short, Simple, but Still of Uncertain Value SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Editorial Material ID QUALITY-OF-LIFE; EMPHYSEMA C1 [Kaplan, Robert M.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD USA. RP Kaplan, RM (reprint author), Off Behav & Social Sci Res, 31 Ctr Dr,Room B1C19, Bethesda, MD 20892 USA. EM Robert.kaplan@nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 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 1 EP 2 DI 10.3109/15412555.2012.651935 PG 2 WC Respiratory System SC Respiratory System GA 884XY UT WOS:000299743400001 PM 22292591 ER PT J AU Byrnes, C Lee, YT Donahue, RE Miller, JL AF Byrnes, Colleen Lee, Y. Terry Donahue, Robert E. Miller, Jeffery L. TI Identification of a cross-reacting, monoclonal anti-human CD233 antibody for identification and sorting of rhesus macaque erythrocytes SO CYTOMETRY PART A LA English DT Article DE CD233; rhesus macaque; erythrocyte; malaria ID EMBRYONIC STEM-CELLS; MALARIA VACCINE; BAND-3 PROTEIN; MONKEYS; IMMUNOGENICITY; PARAMETERS; EPITOPES; INVASION; RECEPTOR; DOMAIN AB Erythroid biology research involving rhesus macaques has been applied to several topics including malaria, hemoglobinopathy and gene therapy research. However, analyses of the rhesus red blood cells are limited by the inability to identify and sort those cells in research blood samples using flow cytometry. Here it is reported that the BRIC 6 hybridoma clone raised to the human erythroid surface molecule (referred to as CD233, Band 3, AE1, or SLC4A1) produces cross-reactive and erythroid-specific antibodies for flow cytometric detection and sorting of rhesus macaque erythrocytes. (C) 2011 International Society for Advancement of Cytometry C1 [Byrnes, Colleen; Lee, Y. Terry; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Donahue, Robert E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Miller, JL (reprint author), NIDDK, Mol Med Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9N311, Bethesda, MD 20892 USA. EM jm7f@nih.gov FU National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart Lung and Blood Institute FX The authors thank the NIH Intramural primate research community for helpful conversations and related reagents. This U.S. government research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and National Heart Lung and Blood Institute. NR 22 TC 0 Z9 0 U1 0 U2 1 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 165 EP 168 DI 10.1002/cyto.a.22005 PG 4 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 880AQ UT WOS:000299376900011 PM 22170815 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 Seaquist, ER Miller, ME Bonds, DE Feinglos, M Goff, DC Peterson, K Senior, P AF Seaquist, Elizabeth R. Miller, Michael E. Bonds, Denise E. Feinglos, Mark Goff, David C., Jr. Peterson, Kevin Senior, Peter CA ACCORD Investigators TI The Impact of Frequent and Unrecognized Hypoglycemia on Mortality in the ACCORD Study SO DIABETES CARE LA English DT Article AB OBJECTIVE-The aim of this study was to examine the relationship between frequent and unrecognized hypoglycemia and mortality in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study cohort. RESEARCH DESIGN AND METHODS-A total of 10,096 ACCORD study participants with follow-up for both hypoglycemia and mortality were included. Hazard ratios (95% CIs) relating the risk of death to the updated annualized number of hypoglycemic episodes and the updated annualized number of intervals with unrecognized hypoglycemia were obtained using Cox proportional hazards regression models, allowing for these hypoglycemia variables as time-dependent covariates and controlling for the baseline covariates. RESULTS-Participants in the intensive group reported a mean of 1.06 hypoglycemic episodes (self-monitored blood glucose <70 mg/dL or <3.9 mmol/L) in the 7 days preceding their regular 4-month visit, whereas participants in the standard group reported an average of 0.29 episodes. Unrecognized hypoglycemia was reported, on average, at 5.8% of the intensive group 4-month visits and 2.6% of the standard group visits. Hazard ratios for mortality in models including frequency of hypoglycemic episodes were 0.93 (95% CI 0.9-0.97; P < 0.001) for participants in the intensive group and 0.98 (0.91-1.06; P = 0.615) for participants in the standard group. The hazard ratios for mortality in models, including unrecognized hypoglycemia, were not statistically significant for either group. CONCLUSIONS-Recognized and unrecognized hypoglycemia was more common in the intensive group than in the standard group. In the intensive group of the ACCORD study, a small but statistically significant inverse relationship of uncertain clinical importance was identified between the number of hypoglycemic episodes and the risk of death among participants. C1 [Seaquist, Elizabeth R.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Miller, Michael E.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Bonds, Denise E.] NHLBI, Bethesda, MD 20892 USA. [Feinglos, Mark] Duke Univ, Med Ctr, Div Endocrinol Metab & Nutr, Durham, NC USA. [Goff, David C., Jr.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA. [Peterson, Kevin] Univ Minnesota, Dept Family Med, Minneapolis, MN 55455 USA. [Senior, Peter] Univ Alberta, Dept Med, Sch Med, Div Endocrinol, Edmonton, AB, Canada. RP Seaquist, ER (reprint author), Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA. EM seaqu001@umn.edu RI Senior, Peter/E-3031-2013; OI Senior, Peter/0000-0003-1033-8673; Peterson, Kevin/0000-0002-6914-8586 FU National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035, IAA-Y1-HC-1010]; National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; general clinical research centers FX This work was supported by grants (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035, and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute and by other branches of the National Institutes of Health, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; and by general clinical research centers. NR 10 TC 54 Z9 57 U1 1 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 409 EP 414 DI 10.2337/dc11-0996 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 886LN UT WOS:000299856000037 PM 22179956 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 Houdayer, E Beck, S Karabanov, A Poston, B Hallett, M AF Houdayer, Elise Beck, Sandra Karabanov, Anke Poston, Brach Hallett, Mark TI The differential modulation of the ventral premotor-motor interaction during movement initiation is deficient in patients with focal hand dystonia SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE motor cortex; movement disorders; surround inhibition; transcranial magnetic stimulation; ventral premotor cortex ID TRANSCRANIAL MAGNETIC STIMULATION; WRITERS CRAMP; SURROUND INHIBITION; FRONTAL-LOBE; CORTICOSPINAL PROJECTIONS; SENSORIMOTOR INTEGRATION; TORSION DYSTONIA; LATERAL SURFACE; CORTEX OUTPUTS; BASAL GANGLIA AB A major feature of focal hand dystonia (FHD) pathophysiology is the loss of inhibition. One inhibitory process, surround inhibition, for which the cortical mechanisms are still unknown, is abnormal in FHD. As the ventral premotor cortex (PMv) plays a key role in the sensorimotor processing involved in shaping finger movements and has many projections onto the primary motor cortex (M1), we hypothesized that the PMvM1 connections might play a role in surround inhibition. A paired-pulse transcranial magnetic stimulation paradigm was used in order to evaluate and compare the PMvM1 interactions during different phases (rest, preparation and execution) of an index finger movement in patients with FHD and controls. A sub-threshold conditioning pulse (80% resting motor threshold) was applied to the PMv at 6 ms before M1 stimulation. The right abductor pollicis brevis, a surround muscle, was the target muscle. In healthy controls, the results showed that PMv stimulation induced an ipsilateral ventral premotormotor inhibition at rest. This cortico-cortical interaction changed into an early facilitation (100 ms before movement onset) and turned back to inhibition 50 ms later. In patients with FHD, this PMvM1 interaction and its modulation were absent. Our results show that, although the ipsilateral ventral premotormotor inhibition does not play a key role in the genesis of surround inhibition, PMv has a dynamic influence on M1 excitability during the early steps of motor execution. The impaired cortico-cortical interactions observed in patients with FHD might contribute, at least in part, to the abnormal motor command. C1 [Houdayer, Elise; Beck, Sandra; Karabanov, Anke; Poston, Brach; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Beck, Sandra] Univ Freiburg, Dept Neurol & Clin Neurophysiol, D-79106 Freiburg, Germany. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, 10 Ctr Dr,MSC 1428,Bldg 10,Room 7D37, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov OI Karabanov, Anke Ninija/0000-0003-1874-393X FU National Institute of Neurological Disorders and Stroke; Fyssen Foundation FX This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program. E. H. was funded by the Fyssen Foundation. NR 50 TC 11 Z9 11 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2012 VL 35 IS 3 BP 478 EP 485 DI 10.1111/j.1460-9568.2011.07960.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 884GL UT WOS:000299692800014 PM 22288483 ER PT J AU Kleykamp, BA Griffiths, RR McCann, UD Smith, MT Mintzer, MZ AF Kleykamp, Bethea A. Griffiths, Roland R. McCann, Una D. Smith, Michael T. Mintzer, Miriam Z. TI Acute Effects of Zolpidem Extended-Release on Cognitive Performance and Sleep in Healthy Males After Repeated Nightly Use SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE zolpidem; Ambien; psychomotor; cognition; tolerance; memory ID TERM BENZODIAZEPINE USE; MEMORY FUNCTIONS; PSYCHOMOTOR PERFORMANCE; RETROGRADE FACILITATION; ATTENTIONAL PROCESSES; ADMINISTRATION 5; ABUSE LIABILITY; SEMANTIC MEMORY; TRIAZOLAM; LORAZEPAM AB The extended-release formulation of zolpidem (Ambien CR) is approved for the treatment of insomnia without a treatment duration limit. Acutely zolpidem impairs performance, and no research to date has examined whether tolerance develops to these performance impairments during nighttime awakening. The present double-blind, placebo-controlled study examined whether tolerance develops to zolpidem-induced acute performance impairment after repeated (22-30 days) nightly use. Effects of bedtime administration of zolpidem extended-release (ZOL; 12.5 mg) were tested on a battery of performance measures assessed during a forced nighttime awakening in 15 healthy male volunteers who completed overnight polysomnographic recording sessions in our laboratory at baseline and after approximately a month of at-home ZOL. As expected, bedtime ZOL administration was associated with changes in sleep architecture and impairments across all performance domains during nighttime testing (psychomotor function, attention, working memory, episodic memory, metacognition) with no residual next morning impairment. Tolerance did not develop to the observed ZOL-related impairments on any outcome. Possible evidence of acute abstinence effects after discontinuation of ZOL was observed on some performance and sleep outcomes. Overall, these findings suggest that performance is significantly impaired during nighttime awakening even after a month of nightly ZOL administration, and these impairments could significantly impact safety should nighttime awakening require unimpaired functioning (e.g., driving; combat-related activities in the military). C1 [Kleykamp, Bethea A.] NIDA, IRTA, Nicotine Psychopharmacol Sect, Clin Pharmacol & Therapeut Branch,Intramural Res, Baltimore, MD 21224 USA. [Griffiths, Roland R.; McCann, Una D.; Smith, Michael T.; Mintzer, Miriam Z.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. RP Kleykamp, BA (reprint author), NIDA, IRTA, Nicotine Psychopharmacol Sect, Clin Pharmacol & Therapeut Branch,Intramural Res, 251 Bayview Blvd,Room 01A941, Baltimore, MD 21224 USA. EM annie.kleykamp@nih.gov FU National Institute on Drug Abuse [DA-11936, DA-07209]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR-054871]; National Center of Research Resources, National Institutes of Health [M01RR-02719] FX We thank Crystal Barnhouser, Jared Saletin, and Jenna Cohen for protocol management and technical assistance, John Yingling for computer programming assistance and technical support, and Paul Nuzzo for assistance with the data analysis. Portions of these data were presented at the 72nd annual meeting of the College on Problems of Drug Dependence. This project was supported by National Institute on Drug Abuse Grants DA-11936 and DA-07209, National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant AR-054871, and Grant M01RR-02719 from the Clinical Research Unit Program of the National Center of Research Resources, National Institutes of Health. NR 51 TC 6 Z9 6 U1 7 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD FEB PY 2012 VL 20 IS 1 BP 28 EP 39 DI 10.1037/a0025237 PG 12 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 886OR UT WOS:000299864200004 PM 21928913 ER PT J AU Amiri-Kordestani, L Tan, AR Swain, SM AF Amiri-Kordestani, Laleh Tan, Antoinette R. Swain, Sandra M. TI Pazopanib for the treatment of breast cancer SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Editorial Material DE breast cancer; pazopanib; PDGFR; tyrosine kinase inhibitor; VEGF; VEGFR ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; TYROSINE KINASE INHIBITOR; ADVANCED SOLID TUMORS; BETA-RECEPTOR EXPRESSION; PHASE-II; FACTOR PDGF; PROGNOSTIC-SIGNIFICANCE; ANGIOGENIC FACTORS; SUNITINIB MALATE AB Introduction: Several clinical trials have shown clinical benefit of angiogenesis inhibitors in the treatment of solid tumors. Pazopanib is a multitargeted tyrosine kinase inhibitor that is currently approved for the treatment of patients with advanced renal cell carcinoma (RCC). Areas covered: In this article, the clinical development of pazopanib as it relates to breast cancer is reviewed including its evaluation in clinical trials and side effect profile. Preclinical data show the anti-tumor activity of pazopanib in animal models. Several trials of pazopanib monotherapy and combination therapy in breast cancer have been completed or are underway. Expert opinion: The development of biomarkers predictive of response and toxicity to angiogenesis inhibitors remains a challenging endeavor and is necessary to help guide treatment decision. C1 [Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, MedStar Hlth, Washington, DC 20010 USA. [Amiri-Kordestani, Laleh] NCI, Bethesda, MD 20892 USA. [Tan, Antoinette R.] Canc Inst New Jersey,Med Oncol, New Brunswick, NJ USA. RP Swain, SM (reprint author), Washington Hosp Ctr, Washington Canc Inst, MedStar Hlth, Washington, DC 20010 USA. EM sandra.m.swain@medstar.net OI Swain, Sandra/0000-0002-1320-3830 NR 67 TC 7 Z9 7 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD FEB PY 2012 VL 21 IS 2 BP 217 EP 225 DI 10.1517/13543784.2012.652304 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 875UD UT WOS:000299059800009 PM 22233389 ER PT J AU Trotter, JF Everhart, JE AF Trotter, James F. Everhart, James E. TI Outcomes Among Living Liver Donors SO GASTROENTEROLOGY LA English DT Editorial Material ID HEPATIC LOBE DONORS; QUALITY-OF-LIFE; UNITED-STATES; TRANSPLANTATION; DONATION C1 [Trotter, James F.] Baylor Univ, Med Ctr, Dallas, TX 75246 USA. [Everhart, James E.] NIDDK, Bethesda, MD USA. RP Trotter, JF (reprint author), Baylor Univ, Med Ctr, 3410 Worth St,Suite 860, Dallas, TX 75246 USA. EM james.trotter@baylorhealth.edu NR 16 TC 0 Z9 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2012 VL 142 IS 2 BP 207 EP 210 DI 10.1053/j.gastro.2011.12.018 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 882CV UT WOS:000299540000022 PM 22198246 ER PT J AU Catalan, MA Flores, CA Gonzalez-Begne, M Zhang, Y Sepulveda, FV Melvin, JE AF Catalan, Marcelo A. Flores, Carlos A. Gonzalez-Begne, Mireya Zhang, Yan Sepulveda, Francisco V. Melvin, James E. TI Severe Defects in Absorptive Ion Transport in Distal Colons of Mice That Lack ClC-2 Channels SO GASTROENTEROLOGY LA English DT Article DE NaCl Absorption; KCl Absorption; Fluid Secretory Defects; Intestinal Epithelial Cells ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS; CHLORIDE CHANNEL; ELECTROLYTE TRANSPORT; SMALL-INTESTINE; ACINAR-CELLS; SECRETION; RAT; EPITHELIUM; ACTIVATION AB BACKGROUND & AIMS: The fluid secretion model predicts that intestinal obstruction disorders can be alleviated by promoting epithelial Cl- secretion. The adenosine 3',5'-cyclic monophosphate (cAMP)-activated anion channel CFTR mediates Cl- -dependent fluid secretion in the intestine. Although the role of the ClC-2 channel has not been determined in the intestine, this voltage-gated Cl- channel might compensate for the secretory defects observed in patients with cystic fibrosis and other chronic constipation disorders. We investigated whether mice that lack ClC-2 channels (Clcn2(-/-)) have defects in intestinal ion transport. METHODS: Immunolocalization and immunoblot analyses were used to determine the cellular localization and the amount of ClC-2 expressed in mouse early distal colon (EDC) and late distal colon (LDC). Colon sheets from wild-type and Clcn2(-/-) littermates were mounted in Ussing chambers to determine transepithelial bioelectrical parameters and Na+, K+, and Cl- fluxes. RESULTS: Expression of ClC-2 was higher in the basolateral membrane of surface cells in the EDC compared with the LDC, with little expression in crypts. Neither cAMP nor Ca2+-induced secretion of Cl- was affected in the EDC or LDC of Clcn2(-/-) mice, whereas the amiloride-sensitive short-circuit current was increased approximately 3-fold in Clcn2(-/-) EDC compared with control littermates. Conversely, electroneutral Na+, K+, and Cl- absorption was dramatically reduced in colons of Clcn2(-/-) mice. CONCLUSIONS: Basolateral ClC-2 channels are required for colonic electroneutral absorption of NaCl and KCl. The increase in the amiloride-sensitive short-circuit current in Clcn2(-/-) mice revealed a compensatory mechanism that is activated in the colons of mice that lack the ClC-2 channel. C1 [Catalan, Marcelo A.; Zhang, Yan; Melvin, James E.] Natl Inst Dent & Craniofacial Res, Secretory Mech & Dysfunct Sect, NIH, Bethesda, MD 20892 USA. [Flores, Carlos A.; Sepulveda, Francisco V.] Ctr Estudios Cient, Valdivia, Chile. [Gonzalez-Begne, Mireya] Univ Rochester, Med Ctr, Ctr Oral Biol, Rochester, NY 14642 USA. RP Melvin, JE (reprint author), Natl Inst Dent & Craniofacial Res, Secretory Mech & Dysfunct Sect, NIH, 10 Ctr Dr,Bldg 10,Room 5-2531, Bethesda, MD 20892 USA. EM james.melvin@nih.gov OI Catalan, Marcelo/0000-0003-3544-2821 FU National Institutes of Health [DE09621]; Takeda Pharmaceuticals North America, Inc; Fondecyt [11100408]; Conicyt-PFB; Gobierno Regional de Los Rios FX Supported in part by the National Institutes of Health Intramural Research Program and research grants from the National Institutes of Health (DE09621) and Takeda Pharmaceuticals North America, Inc (to J.E.M.) and Fondecyt (11100408) (to C. A. F.). Centro de Estudios Cientificos is funded by Conicyt-PFB and Gobierno Regional de Los Rios. NR 45 TC 11 Z9 11 U1 2 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 346 EP 354 DI 10.1053/j.gastro.2011.10.037 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 882CV UT WOS:000299540000041 PM 22079595 ER PT J AU Nakamoto, N Ebinuma, H Kanai, T Chu, PS Ono, Y Mikami, Y Ojiro, K Lipp, M Love, PE Saito, H Hibi, T AF Nakamoto, Nobuhiro Ebinuma, Hirotoshi Kanai, Takanori Chu, Po-Sung Ono, Yuichi Mikami, Yohei Ojiro, Keisuke Lipp, Martin Love, Paul E. Saito, Hidetsugu Hibi, Toshifumi TI CCR9(+) Macrophages Are Required for Acute Liver Inflammation in Mouse Models of Hepatitis SO GASTROENTEROLOGY LA English DT Article DE Immune Regulation; Hepatic Disease; Chemokine Receptor; T-Cell Activation ID PLASMACYTOID DENDRITIC CELLS; T-CELLS; CROHNS-DISEASE; CONCANAVALIN-A; SIGLEC-H; RECEPTOR; PRECURSORS; TOLERANCE; LYMPHOCYTES; CCL25/CCR9 AB BACKGROUND & AIMS: Antigen-presenting cells (APCs) are involved in the induction of liver inflammation. We investigated the roles of specific APCs in the pathogenesis of acute liver injury in mice. METHODS: We used concanavalin A (con A) or carbon tetrachloride to induce acute liver inflammation in mice and studied the roles of macrophages that express CCR9. RESULTS: After injection of con A, we detected CCR9(+)CD11b(+)CD11c(-)macrophages that express tumor necrosis factor (TNF)-alpha in livers of mice, whereas CCR9(+) Siglec-H(+)CD11b(-)CD11c(low) plasmacytoid DCs (pDCs), which are abundant in normal livers, disappeared. The CCR9(+) macrophages were also detected in the livers of RAG-2(-/-) mice, which lack lymphocytes and natural killer T cells, after injection of con A. Under inflammatory conditions, CCR9(+) macrophages induced naive CD4(+) T cells to become interferon gamma-producing Th1 cells in vivo and in vitro. CCR9 (/) mice injected with con A did not develop hepatitis unless they also received CCR9(+) macrophages from mice that received con A; more CCR9(+) macrophages accumulated in their inflamed livers than CCR9(+) pDCs, CCR9(-)pDCs, or CCR9(-)macrophages isolated from mice that had received injections of con A. Levels of CCL25 messenger RNA increased in livers after injection of con A; neutralizing antibodies against CCL25 reduced the induction of hepatitis by con A by blocking the migration of CCR9(+) macrophages and their production of TNF-alpha. Peripheral blood samples from patients with acute hepatitis had greater numbers of TNF-alpha-producing CCR9(+)CD14(+) CD16(high) monocytes than controls. CONCLUSIONS: CCR9(+)macrophages contribute to the induction of acute liver inflammation in mouse models of hepatitis. C1 [Nakamoto, Nobuhiro; Ebinuma, Hirotoshi; Kanai, Takanori; Chu, Po-Sung; Ono, Yuichi; Mikami, Yohei; Ojiro, Keisuke; Saito, Hidetsugu; Hibi, Toshifumi] Keio Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Tokyo 1808582, Japan. [Lipp, Martin] Max Delbruck Ctr Mol Med, Dept Tumor Genet & Immunogenet, Berlin, Germany. [Love, Paul E.] NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Kanai, T (reprint author), Keio Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Tokyo 1808582, Japan. EM takagast@sc.itc.keio.ac.jp; thibi@sc.itc.keio.ac.jp FU Japanese Ministry of Education, Culture, Sports, Science and Technology; Japanese Ministry of Health, Labour and Welfare; Japan Medical Association; Foundation for Advancement of International Science; Keio University FX Supported part by grants-in-aid for Scientific Research, Scientific Research on Priority Areas, Exploratory Research and Creative Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology; the Japanese Ministry of Health, Labour and Welfare; the Japan Medical Association; Foundation for Advancement of International Science; and Keio University Medical Fund.; Writing assistance was provided by Dr Peter Hawkes (Kansai Language College) and Edanz Group Ltd and funded by grants-in-aid for Scientific Research, Scientific Research on Priority Areas, Exploratory Research. NR 30 TC 25 Z9 25 U1 1 U2 8 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 366 EP 376 DI 10.1053/j.gastro.2011.10.039 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 882CV UT WOS:000299540000043 PM 22079594 ER PT J AU Vahabzadeh, B Seetharam, AB Cook, MB Wani, S Rastogi, A Bansal, A Early, DS Sharma, P AF Vahabzadeh, Babac Seetharam, Anil B. Cook, Michael B. Wani, Sachin Rastogi, Amit Bansal, Ajay Early, Dayna S. Sharma, Prateek TI Validation of the Prague C & M criteria for the endoscopic grading of Barrett's esophagus by gastroenterology trainees: a multicenter study SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID GASTROESOPHAGEAL-REFLUX; EARLY NEOPLASIA; RISK-FACTORS; ADENOCARCINOMA; LENGTH; RELIABILITY; DYSPLASIA; PROGRESSION; DIAGNOSIS; SIZE AB Background: The Prague C & M criteria, developed for the endoscopic grading of Barrett's esophagus (BE), (C = circumferential length, M = maximal length) were previously validated among a panel of 29 expert encloscopists with a special interest in BE. Its performance among gastroenterology trainees is unknown. Objective: To test interobserver agreement among gastroenterology trainees for the Prague C & M criteria, identification of the gastroesophageal junction (GEJ) and the diaphragmatic hiatus. Design: A prospective study. Setting: Two tertiary referral centers. Patients and Interventions: Standardized endoscopic videos were used. Main Outcome Measurements: Interobserver agreement. Results: Eighteen high-quality videos (normal esophagus, short and long lengths of BE, equally distributed) were independently evaluated by 18 gastroenterology trainees (year 1, n = 5; year 2, n = 6; year 3, n = 7) after administration of a formal teaching module by an expert endoscopist. Overall intraclass correlation coefficients for assessment of the C and M extent of the endoscopic BE segment above the GEJ were 0.94 (95% CI, 0.89-0.98) and 0.96 (95% CI, 0.94-0.98), respectively. The overall intraclass correlation coefficients for GEJ and diaphragmatic hiatus location recognition were 0.92 (0.86-0.96) and 0.90 (0.82-0.95), respectively. The year of training did not affect interobserver agreement. Limitations: The use of videos for encloscopic evaluation. Conclusion: After standardized teaching, the Prague C & M criteria have high overall validity among gastroenterology trainees irrespective of the level of training for endoscopic evaluation of visualized BE lengths as well as key endoscopic landmarks. (Gastrointest Endosc 2012;75:236-41.) C1 [Vahabzadeh, Babac; Rastogi, Amit; Bansal, Ajay; Sharma, Prateek] Vet Affairs Med Ctr, Kansas City, MO USA. [Vahabzadeh, Babac; Rastogi, Amit; Bansal, Ajay; Sharma, Prateek] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Seetharam, Anil B.; Wani, Sachin; Early, Dayna S.] Washington Univ, Sch Med, St Louis, MO USA. [Cook, Michael B.] NCI, Bethesda, MD 20892 USA. RP Sharma, P (reprint author), Univ Kansas, Sch Med, Dept Vet Affairs Med Ctr, 4801 E Linwood Blvd, Kansas City, MO 64128 USA. RI Cook, Michael/A-5641-2009 OI Cook, Michael/0000-0002-0533-7302 FU Intramural VA [VA999999] NR 24 TC 23 Z9 23 U1 1 U2 2 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 236 EP 241 DI 10.1016/j.gie.2011.09.017 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 885BF UT WOS:000299752800002 PM 22248595 ER PT J AU Zhu, JJ Nguyen, MT Nakamura, E Yang, JM Mackem, S AF Zhu, Jianjian Minh-Thanh Nguyen Nakamura, Eiichiro Yang, Junming Mackem, Susan TI Cre-mediated recombination can induce apoptosis in vivo by activating the p53 DNA damage-induced pathway SO GENESIS LA English DT Article DE transgenic mice; loxP sites; Cre recombinase; apoptosis ID SITE-SPECIFIC RECOMBINATION; SONIC-HEDGEHOG; LIMB BUD; INVERTED REPEATS; MAMMALIAN-CELLS; TRANSGENIC MICE; LATERAL PLATE; EXPRESSION; MOUSE; GENE AB Cre-mediated apoptosis has been observed in many contexts in mice expressing Cre-recombinase and can confound the analysis of genetically engineered conditional mutant or transgenic alleles. Several mechanisms have been proposed to explain this phenomenon. We find that the degree of apoptosis induced correlates roughly with the copy number of loxP sites present in the genome and that some level of increased apoptosis accompanies the presence of even only a few loxP sites, as occurs in conditional floxed alleles. Cre-induced apoptosis in this context is completely p53-dependent, suggesting that the apoptosis is stimulated by p53 activation in response to DNA damage incurred during the process of Cre-mediated recombination. genesis 50:102111, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Zhu, Jianjian; Minh-Thanh Nguyen; Nakamura, Eiichiro; Yang, Junming; Mackem, Susan] NCI, Ctr Canc Res, Canc & Dev Biol Lab, Ft Detrick, MD 21702 USA. [Minh-Thanh Nguyen] Univ Cincinnati, Dept Ophthalmol, Cincinnati, OH 45221 USA. [Nakamura, Eiichiro] Univ Occupat & Environm Hlth, Dept Orthoped Surg, Kitakyushu Fukuoka 8078555, Japan. RP Mackem, S (reprint author), NCI, Ctr Canc Res, Canc & Dev Biol Lab, 1050 Boyles St,Bldg 539,Room 121A, Ft Detrick, MD 21702 USA. EM smack@helix.nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX Contract grant sponsor: Center for Cancer Research, National Cancer Institute, NIH NR 41 TC 8 Z9 8 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-954X J9 GENESIS JI Genesis PD FEB PY 2012 VL 50 IS 2 BP 102 EP 111 DI 10.1002/dvg.20799 PG 10 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 886EQ UT WOS:000299835500003 PM 21913308 ER PT J AU Berquam-Vrieze, KE Swing, DA Tessarollo, L Dupuy, AJ AF Berquam-Vrieze, Katherine E. Swing, Deborah A. Tessarollo, Lino Dupuy, Adam J. TI Characterization of transgenic mice expressing cancer-associated variants of human NOTCH1 SO GENESIS LA English DT Article DE mouse models of cancer; BAC recombineering; BAC transgenesis ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACTIVATED NOTCH1; PROGRESSION; MUTATIONS; APOPTOSIS; BINDING; GENES; CELLS; CD4 AB The Notch1 receptor plays a critical role in cell fate decisions during development. Activation of Notch signaling has been implicated in several types of cancer, particularly T-cell acute lymphoblastic leukemia (T-ALL). Consequently, several transgenic mouse strains have been made to study the role of Notch1 in T-ALL. However, the existing Notch1 transgenic lines mimic a translocation event found in only similar to 1% of T-ALL cases. Here we describe three novel NOTCH1 transgenic mouse strains that have Cre-inducible expression of the entire human NOTCH1 locus, each possessing a common mutation found in T-ALL. Unlike existing Notch1 transgenic strains, these NOTCH1 transgenic strains express full-length receptors from anendogenous human promoter that should be susceptible to a number of Notch antagonists that have recently been developed. These strains will allow researchers to modulate Notch signaling to study bothnormal development and cancer biology. genesis 50:112118, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Berquam-Vrieze, Katherine E.; Dupuy, Adam J.] Univ Iowa, Carver Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. [Swing, Deborah A.; Tessarollo, Lino] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. RP Dupuy, AJ (reprint author), Univ Iowa, Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. EM adam-dupuy@uiowa.edu FU NCI NIH HHS [R01 CA130867, R01 CA130867-04] NR 29 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-954X J9 GENESIS JI Genesis PD FEB PY 2012 VL 50 IS 2 BP 112 EP 118 DI 10.1002/dvg.20798 PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 886EQ UT WOS:000299835500004 PM 21898766 ER PT J AU Hendrickson, AEW Oberg, AL Glaser, G Camoriano, JK Peethambaram, PP Colon-Otero, G Erlichman, C Ivy, SP Kaufmann, SH Karnitz, LM Haluska, P AF Hendrickson, Andrea E. Wahner Oberg, Ann L. Glaser, Gretchen Camoriano, John K. Peethambaram, Prema P. Colon-Otero, Gerardo Erlichman, Charles Ivy, S. Percy Kaufmann, Scott H. Karnitz, Larry M. Haluska, Paul TI A phase II study of gemcitabine in combination with tanespimycin in advanced epithelial ovarian and primary peritoneal carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Phase I/II trials; Tanespimycin; Gemcitabine; Ovarian cancer; Peritoneal cancer; Heat shock protein 90 ID REFRACTORY ADVANCED CANCERS; LEUKEMIA-CELLS; IN-VIVO; HSP90; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; INHIBITION; TRIAL; GELDANAMYCIN; HEAT-SHOCK-PROTEIN-90; ACTIVATION AB Objective. To evaluate the efficacy and biological effects of the gemcitabine/tanespimycin combination in patients with advanced ovarian and peritoneal cancer. To assess the effect of tanespimycin on tumor cells, levels of the chaperone proteins HSP90 and HSP70 were examined in peripheral blood mononuclear cells (PBMC) and paired tumor biopsy lysates. Methods. Two-cohort phase II clinical trial. Patients were grouped according to prior gemcitabine therapy. All participants received tanespimycin 154 mg/m(2) on days 1 and 9 of cycle 1 and days 2 and 9 of subsequent cycles. Patients also received gemcitabine 750 mg/m(2) on day 8 of the first treatment cycle and days 1 and 8 of subsequent cycles. Results. The tanespimycin/gemcitabine combination induced a partial response in 1 gemcitabine naive patient and no partial responses in gemcitabine resistant patients. Stable disease was seen in 6 patients (2 gemcitabine naive and 4 gemcitabine resistant). The most common toxicities were hematologic (anemia and neutropenia) as well as nausea and vomiting. Immunoblotting demonstrated limited upregulation of HSP70 but little or no change in levels of most client proteins in PBMC and paired tumor samples. Conclusions. Although well tolerated, the tanespimycin/gemcitabine combination exhibited limited anticancer activity in patients with advanced epithelial ovarian and primary peritoneal carcinoma, perhaps because of failure to significantly downregulate the client proteins at clinically achievable exposures. (C) 2011 Elsevier Inc. All rights reserved. C1 [Hendrickson, Andrea E. Wahner; Peethambaram, Prema P.; Erlichman, Charles; Haluska, Paul] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA. [Oberg, Ann L.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Glaser, Gretchen] Mayo Clin, Div Gynecol Oncol, Rochester, MN 55905 USA. [Colon-Otero, Gerardo] Mayo Clin, Div Hematol Oncol, Jacksonville, FL 32224 USA. [Camoriano, John K.] Mayo Clin, Div Hematol Oncol, Scottsdale, AZ 85054 USA. [Ivy, S. Percy] NCI, Rockville, MD 20852 USA. [Kaufmann, Scott H.; Karnitz, Larry M.] Mayo Clin, Div Oncol Res, Rochester, MN 55905 USA. [Kaufmann, Scott H.; Karnitz, Larry M.] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA. RP Haluska, P (reprint author), Mayo Clin, Div Med Oncol, Gonda 10,200 1st St SW, Rochester, MN 55905 USA. EM haluska.paul@mayo.edu OI Kaufmann, Scott/0000-0002-4900-7145 FU Mayo Phase 2 [N01-CM 62205, K12 CA090628, R01 CA104378] FX Supported by The Mayo Phase 2 contract N01-CM 62205 (C.E.), K12 CA090628 (P. H.) and R01 CA104378 (L.M.K.). NR 31 TC 13 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2012 VL 124 IS 2 BP 210 EP 215 DI 10.1016/j.ygyno.2011.10.002 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 885UE UT WOS:000299805500007 PM 22047770 ER PT J AU Francis, JH Kleinerman, RA Seddon, JM Abramson, DH AF Francis, Jasmine H. Kleinerman, Ruth A. Seddon, Johanna M. Abramson, David H. TI Increased risk of secondary uterine leiomyosarcoma in hereditary retinoblastoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Retinoblastoma; Uterine leiomyosarcoma; Secondary cancers ID SOFT-TISSUE SARCOMAS; ALTERED PATTERNS; TUMOR-SUPPRESSOR; CANCER INCIDENCE; URINARY-BLADDER; FOLLOW-UP; SURVIVORS; CHILDHOOD; MUTATIONS; UTERUS AB Objective. In the US, second non-ocular malignancies are the primary cause of death in retinoblastoma survivors with the germline RB1 mutation. Soft tissue sarcomas are one of the most likely malignancies to pose a risk to these patients, with leiomyosarcoma (LMS) being the most common subtype. As our cohort is followed for a longer period, we discover new second malignancy risks for these patients. Methods. We estimated the risk for uterine leiomyosarcoma (ULMS) in a cohort of 1854 patients with retinoblastoma who were diagnosed at two US institutions from 1914 through 1996. The standardized incidence ratio and excess absolute risk were calculated by comparison with population data from the Connecticut Tumor Registry or from National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. The cumulative risk at 50 years of age was also calculated. Results. Seven of 525 female hereditary retinoblastoma patients developed ULMS. Five of these patients were used in the risk analysis, resulting in an excess risk of 3.87 per 10,000 women. Among hereditary patients who developed ULMS the excess risk increases dramatically with age: to 20/10,000 for female hereditary retinoblastoma patients aged between 30 and 39 years, and to 27/10,000 for patients aged 40+ years. Conclusion. There is a substantial excess risk of ULMS in female hereditary retinoblastoma patients. As more patients survive into their thirties, this number is likely to increase. These findings raise the question of early childbearing, screening and prophylactic measures in hereditary retinoblastoma patients: all issues that would benefit from confirmation from other retinoblastoma cohorts, to allow for better guided counsel of these patients. (C) 2011 Elsevier Inc. All rights reserved. C1 [Francis, Jasmine H.; Abramson, David H.] Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10021 USA. [Francis, Jasmine H.] New York Eye & Ear Infirm, New York, NY 10003 USA. [Kleinerman, Ruth A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Seddon, Johanna M.] Tufts Univ New England Med Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA USA. RP Abramson, DH (reprint author), Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, 70 E 66th St, New York, NY 10021 USA. EM abramsod@mskcc.org OI Kleinerman, Ruth/0000-0001-7415-2478 FU National Institutes of Health; National Cancer Institute, Division of Cancer Epidemiology and Genetics; Fund for Ophthalmic Knowledge FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics and by The Fund for Ophthalmic Knowledge. NR 55 TC 11 Z9 12 U1 0 U2 0 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 254 EP 259 DI 10.1016/j.ygyno.2011.10.019 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 885UE UT WOS:000299805500015 PM 22027510 ER PT J AU Simons-Morton, B Abraido-Lanza, AF Bernhardt, JM Schoenthaler, A Schnitzer, A Allegrante, JP AF Simons-Morton, Bruce Abraido-Lanza, Ana F. Bernhardt, Jay M. Schoenthaler, Antoinette Schnitzer, Amanda Allegrante, John P. TI Demystifying Peer Review SO HEALTH EDUCATION & BEHAVIOR LA English DT Editorial Material C1 [Allegrante, John P.] Columbia Univ, Teachers Coll, Dept Hlth & Behav Studies, New York, NY 10027 USA. [Simons-Morton, Bruce; Allegrante, John P.] NIH, Bethesda, MD 20892 USA. [Bernhardt, Jay M.] Univ Florida, Gainesville, FL USA. [Schoenthaler, Antoinette] NYU, New York, NY USA. [Schnitzer, Amanda] Soc Publ Hlth Educ, Washington, DC USA. RP Allegrante, JP (reprint author), Columbia Univ, Teachers Coll, Dept Hlth & Behav Studies, 525 W 120th St, New York, NY 10027 USA. EM jpa1@columbia.edu OI Bernhardt, Jay/0000-0002-2045-4005; Schoenthaler, Antoinette/0000-0003-4905-5136; Simons-Morton, Bruce/0000-0003-1099-6617 FU Intramural NIH HHS; NCI NIH HHS [R21CA134247]; NIGMS NIH HHS [R25GM62454] NR 5 TC 3 Z9 3 U1 0 U2 2 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 3 EP 7 DI 10.1177/1090198111433309 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 885LN UT WOS:000299780600001 PM 22301900 ER PT J AU Kaphingst, KA Goodman, M Pyke, O Stafford, J Lachance, C AF Kaphingst, Kimberly A. Goodman, Melody Pyke, Owen Stafford, Jewel Lachance, Christina TI Relationship Between Self-Reported Racial Composition of High School and Health Literacy Among Community Health Center Patients SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE community health centers; health disparities; health literacy; residential segregation ID NEWEST VITAL SIGN; ADULT LITERACY; RESIDENTIAL SEGREGATION; AFRICAN-AMERICAN; PRIMARY-CARE; DISPARITIES; SKILLS; POPULATION; BEHAVIOR AB Intervention and policy approaches targeting the societal factors that affect health literacy (e.g., educational systems) could have promise to improve health outcomes, but little research has investigated these factors. This study examined the associations between self-reported racial composition of prior educational and neighborhood contexts and health literacy among 1,061 English- and Spanish-speaking adult community health center patients. The authors found that self-reported racial composition of high school was a significant predictor of health literacy among those who received schooling in the United States, controlling for race/ethnicity, education, age, country of birth, and survey language. Black and Hispanic patients had significantly lower health literacy than White patients within educational strata among those schooled in the United States. The findings revealed substantial disparities in health literacy. Self-reported racial composition of school context was a significant predictor of health literacy. Transdisciplinary, multilevel intervention approaches are likely to be needed to address the health literacy needs of this population. C1 [Kaphingst, Kimberly A.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA. [Goodman, Melody; Pyke, Owen; Stafford, Jewel] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Lachance, Christina] NHGRI, NIH, Bethesda, MD 20892 USA. RP Kaphingst, KA (reprint author), Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, Campus Box 8100, St Louis, MO 63110 USA. EM kkaphingst@gwbmail.wustl.edu RI Goodman, Melody/F-6768-2011 OI Goodman, Melody/0000-0001-8932-624X FU Intramural NIH HHS [Z01 HG200321-04] NR 39 TC 4 Z9 4 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 EI 1552-6127 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD FEB PY 2012 VL 39 IS 1 BP 35 EP 44 DI 10.1177/1090198111406538 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 885LN UT WOS:000299780600005 PM 21636703 ER PT J AU de Heer, HD Balcazar, HG Castro, F Schulz, L AF de Heer, Hendrik Dirk Balcazar, Hector G. Castro, Felipe Schulz, Leslie TI A Path Analysis of a Randomized Promotora de Salud Cardiovascular Disease-Prevention Trial Among At-Risk Hispanic Adults SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE cardiovascular disease; community; education; Hispanic; nutrition; promotoras de salud; structural equation model ID STRUCTURAL EQUATION MODELS; UNITED-STATES; BEHAVIORAL-THEORY; MEXICAN-AMERICANS; HEALTH; ACCULTURATION; LATINO; MORTALITY; COHESION; CONTEXT AB This study assessed effectiveness of an educational community intervention taught by promotoras de salud in reducing cardiovascular disease (CVD) risk among Hispanics using a structural equation modeling (SEM) approach. Model development was guided by a social ecological framework proposing CVD risk reduction through improvement of protective health behaviors, health beliefs, contextual and social factors. Participants were 328 Hispanic adults with at least one CVD risk factor. SEM analyses assessed direct and indirect effects of intervention participation on CVD risk (Framingham score) and latent variables nutrition intake and health beliefs. The model fit was adequate (root mean square error of approximation = .056 [90% confidence interval = .040, .072], comparative fit index = .967, normed fit index = .938, nonnormed fit index = .947). Intervention participation was associated with improved nutritional consumption, but not lower CVD risk. Stronger health beliefs predicted healthier nutritional habits. This project provided evidence for the adequacy of a conceptual framework that can be used to elicit new pathways toward CVD risk reduction among at-risk Hispanic populations. C1 [Balcazar, Hector G.] Univ Texas El Paso, Sch Publ Hlth, El Paso, TX 79902 USA. [de Heer, Hendrik Dirk] NHGRI, Bethesda, MD 20892 USA. [Castro, Felipe] Arizona State Univ, Tempe, AZ USA. [Schulz, Leslie] No Arizona Univ, Flagstaff, AZ 86011 USA. RP Balcazar, HG (reprint author), Univ Texas El Paso, Sch Publ Hlth, El Paso Reg Campus,1100 N Stanton, El Paso, TX 79902 USA. EM hector.g.balcazar@uth.tmc.edu RI de Heer, Hendrik/D-3192-2013 OI de Heer, Hendrik/0000-0002-9241-5021 FU NIMHD NIH HHS [R24 MD0001785-01, R24 MD001785] NR 40 TC 6 Z9 6 U1 0 U2 4 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 77 EP 86 DI 10.1177/1090198111408720 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 885LN UT WOS:000299780600009 PM 21680806 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, Constance E. Everhart, James E. TI Upper limits of normal for alanine aminotransferase activity in the United States population SO HEPATOLOGY LA English DT Article ID TRANSAMINASE-ACTIVITY; REFERENCE INTERVALS; HEALTHY RANGES; BLOOD-DONORS; HEPATITIS-C; SERUM; ALT; PREVALENCE; VALUES AB Alanine aminotransferase (ALT) is an important test for liver disease, yet there is no generally accepted upper limit of normal (ULN) in the United States. Furthermore, the ability of ALT to differentiate persons with and without liver disease is uncertain. We examined cut-offs for ALT for their ability to discriminate between persons with positive hepatitis C virus (HCV) RNA and those at low risk for liver injury in the U.S. population. Among adult participants in the 1999-2008 U.S. National Health and Nutrition Examination Survey, 259 were positive for serum HCV RNA and 3,747 were at low risk for liver injury (i.e., negative HCV RNA and hepatitis B surface antigen, low alcohol consumption, no evidence of diabetes, and normal body mass index and waist circumference). Serum ALT activity was measured centrally. Maximum correct classification was achieved at ALT = 29 IU/L for men (88% sensitivity, 83% specificity) and 22 IU/L (89% sensitivity, 82% specificity) for women. The cut-off for 95% sensitivity was an ALT = 24 IU/L (70% specificity) for men and 18 IU/L (63% specificity) for women. The cut-off for 95% specificity was ALT = 44 IU/L (64% sensitivity) for men and 32 IU/L (59% sensitivity) for women. The area under the curve was 0.929 for men and 0.915 for women. If the cut-offs with the best correct classification were applied to the entire population, 36.4% of men and 28.3% of women would have had abnormal ALT. Conclusion: ALT discriminates persons infected with HCV from those at low risk of liver disease, but would be considered elevated in a large proportion of the U.S. population. (HEPATOLOGY 2012) C1 [Ruhl, Constance E.] Social & Sci Syst Inc, Silver Spring, MD 20910 USA. [Everhart, James E.] NIDDKD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM cruhl@s-3.com FU National Institute of Diabetes and Digestive and Kidney Diseases [HHSN267200700001G] FX This work was supported by a contract from the National Institute of Diabetes and Digestive and Kidney Diseases (HHSN267200700001G). NR 25 TC 33 Z9 34 U1 4 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2012 VL 55 IS 2 BP 447 EP 454 DI 10.1002/hep.24725 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 883KM UT WOS:000299632900013 PM 21987480 ER PT J AU Altekruse, SF McGlynn, KA Dickie, LA Kleiner, DE AF Altekruse, Sean F. McGlynn, Katherine A. Dickie, Lois A. Kleiner, David E. TI Hepatocellular Carcinoma Confirmation, Treatment, and Survival in Surveillance, Epidemiology, and End Results Registries, 1992-2008 SO HEPATOLOGY LA English DT Article ID UNITED-STATES; DIAGNOSIS; TRENDS; RATES AB Approaches to the diagnosis and management of hepatocellular carcinoma (HCC) are improving survival. In the Surveillance, Epidemiology, and End Results-13 registries, HCC stage, histological confirmation, and first-course surgery were examined. Among 21,390 HCC cases diagnosed with follow-up of vital status during 1998-2008, there were 4,727 (22%) with reported first-course invasive liver surgery, local tumor destruction, or both. The proportion with reported liver surgery or ablation was 39% among localized stage cases and only 4% among distant/unstaged cases. Though 70% of cases had histologically confirmed diagnoses, the proportion with confirmed diagnoses was higher among cases with reported invasive surgery (99%), compared to cases receiving ablation (81%) or no reported therapy (65%). Incidence rates of histologically unconfirmed HCC increased faster than those of confirmed HCC from 1992 to 2008 (8% versus 3% per year). Two encouraging findings were that incidence rates of localized-stage HCC increased faster than rates of regional- and distant-stage HCC combined (8% versus 4% per year), and that incidence rates of reported first-course surgery or tumor destruction increased faster than incidence rates of HCC without such therapy (11% versus 7%). Between 1975-1977 and 1998-2007, 5-year cause-specific HCC survival increased from just 3% to 18%. Survival was 84% among transplant recipients, 53% among cases receiving radiofrequency ablation at early stage, 47% among cases undergoing resection, and 35% among cases receiving local tumor destruction. Asian or Pacific Islander cases had significantly better 5-year survival (23%) than white (18%), Hispanic (15%), or black cases (12%). Conclusion: HCC survival is improving, because more cases are diagnosed and treated at early stages. Additional progress may be possible with continued use of clinical surveillance to follow individuals at risk for HCC, enabling early intervention. (HEPATOLOGY 2012;) C1 [Altekruse, Sean F.; Dickie, Lois A.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Kleiner, David E.] NCI, Div Basic Sci, Pathol Lab, Rockville, MD 20852 USA. RP Altekruse, SF (reprint author), NCI, Div Canc Control & Populat Sci, 6116 Execut Blvd,Room 5003, Rockville, MD 20852 USA. EM altekrusesf@mail.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU National Cancer Institute (NCI), Division of Cancer Control and Population Sciences; NIH, National Cancer Institute FX This study was supported by the National Cancer Institute (NCI), Division of Cancer Control and Population Sciences, Surveillance Research Program contracts with SEER Registries and Information Management Services and by the Intramural Research Program of the NIH, National Cancer Institute. NR 25 TC 76 Z9 83 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2012 VL 55 IS 2 BP 476 EP 482 DI 10.1002/hep.24710 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 883KM UT WOS:000299632900016 PM 21953588 ER PT J AU Sastalla, I Tang, SX Crown, D Liu, SH Eckhaus, MA Hewlett, IK Leppla, SH Moayeri, M AF Sastalla, Inka Tang, Shixing Crown, Devorah Liu, Shihui Eckhaus, Michael A. Hewlett, Indira K. Leppla, Stephen H. Moayeri, Mahtab TI Anthrax Edema Toxin Impairs Clearance in Mice SO INFECTION AND IMMUNITY LA English DT Article ID BACILLUS-ANTHRACIS; DIPHTHERIA-TOXIN; PROTECTIVE ANTIGEN; WATER CHANNEL; LETHAL TOXIN; ADENYLATE-CYCLASE; CELL CHEMOTAXIS; AQUAPORIN-2; RECEPTOR; PHOSPHORYLATION AB The anthrax edema toxin (ET) of Bacillus anthracis is composed of the receptor-binding component protective antigen (PA) and of the adenylyl cyclase catalytic moiety, edema factor (EF). Uptake of ET into cells raises intracellular concentrations of the secondary messenger cyclic AMP, thereby impairing or activating host cell functions. We report here on a new consequence of ET action in vivo. We show that in mouse models of toxemia and infection, serum PA concentrations were significantly higher in the presence of enzymatically active EF. These higher concentrations were not caused by ET-induced inhibition of PA endocytosis; on the contrary, ET induced increased PA binding and uptake of the PA oligomer in vitro and in vivo through upregulation of the PA receptors TEM8 and CMG2 in both myeloid and nonmyeloid cells. ET effects on protein clearance from circulation appeared to be global and were not limited to PA. ET also impaired the clearance of ovalbumin, green fluorescent protein, and EF itself, as well as the small molecule biotin when these molecules were coinjected with the toxin. Effects on injected protein levels were not a result of general increase in protein concentrations due to fluid loss. Functional markers for liver and kidney were altered in response to ET. Concomitantly, ET caused phosphorylation and activation of the aquaporin-2 water channel present in the principal cells of the collecting ducts of the kidneys that are responsible for fluid homeostasis. Our data suggest that in vivo, ET alters circulatory protein and small molecule pharmacokinetics by an as-yet-undefined mechanism, thereby potentially allowing a prolonged circulation of anthrax virulence factors such as EF during infection. C1 [Sastalla, Inka; Crown, Devorah; Liu, Shihui; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA. [Tang, Shixing; Hewlett, Indira K.] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Eckhaus, Michael A.] NIH, Diagnost & Res Serv Branch, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Moayeri, M (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mmoayeri@niaid.nih.gov FU National Institutes of Health, National Institute of Allergy and Infectious Diseases; Biodefense Advanced Research and Development Agency, U.S. Department of Health and Human Services FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases and Biodefense Advanced Research and Development Agency, U.S. Department of Health and Human Services. NR 54 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2012 VL 80 IS 2 BP 529 EP 538 DI 10.1128/IAI.05947-11 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 883UU UT WOS:000299661200006 PM 22104108 ER PT J AU Ali, M Bath, P Brady, M Davis, S Diener, HC Donnan, G Fisher, M Hacke, W Hanley, DF Luby, M Tsivgoulis, G Wahlgren, N Warach, S Lees, KR AF Ali, Myzoon Bath, Philip Brady, Marian Davis, Stephen Diener, Hans-Christoph Donnan, Geoffrey Fisher, Marc Hacke, Werner Hanley, Daniel F. Luby, Marie Tsivgoulis, G. Wahlgren, Nils Warach, Steven Lees, Kennedy R. CA VISTA Steering Comm TI Development, expansion, and use of a stroke clinical trials resource for novel exploratory analyses SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE database; secondary analysis; stroke; trial design ID RANDOMIZED CONTROLLED-TRIAL; ACUTE ISCHEMIC-STROKE; ARCHIVE VISTA; ASPIRIN; THROMBOLYSIS; CLOPIDOGREL; DIPYRIDAMOLE; PREVENTION; OUTCOMES; REGISTRY AB Introduction Analysis of reliable registry data can direct future research to influence clinical care. Data from the Virtual International Stroke Trials Archive have been used to test hypotheses and inform trial design. We sought to expand Virtual International Stroke Trials Archive into a broader stroke resource with new opportunities for research and international collaboration. Methods Using procedures initially developed for an acute stroke trial archive, we invited trialists to lodge data on rehabilitation, secondary prevention, intracerebral haemorrhage, imaging, and observational stroke studies. Results We have extended Virtual International Stroke Trials Archive into six subsections: Virtual International Stroke Trials Archive-Acute (n = 28 190 patients' data), Virtual International Stroke Trials Archive-Rehab (n = 10 194), Virtual International Stroke Trials Archive-intracerebral haemorrhage (n = 1829), Virtual International Stroke Trials Archive-Prevention, Virtual International Stroke Trials Archive-Imaging (n = 1300), and Virtual International Stroke Trials Archive-Plus (n = 6573). Enrollment continues, with commitments for the contribution of six further trials to Virtual International Stroke Trials Archive-Prevention, 13 trials to Virtual International Stroke Trials Archive-Rehab, and one registry to Virtual International Stroke Trials Archive-Plus. Data on age, type of stroke, medical history, outcomes by modified Rankin scale and Barthel Index (BI), mortality, and adverse events are available for analyses. The Virtual International Stroke Trials Archive network encourages the development of young investigators and provides opportunities for international peer review and collaboration. Conclusions Application of the original Virtual International Stroke Trials Archive concepts beyond acute stroke trials can extend the value of clinical research at low cost, without threatening commercial or intellectual property interests. This delivers valuable research output to inform the efficiency of future stroke research. We invite stroke researchers to participate actively in Virtual International Stroke Trials Archive and encourage the extension of Virtual International Stroke Trials Archive principles to other disease areas. C1 [Ali, Myzoon; Brady, Marian] Glasgow Caledonian Univ, NMAHP Res Unit, Glasgow G4 0BA, Lanark, Scotland. [Bath, Philip] Univ Nottingham, Inst Neurosci, Nottingham NG7 2RD, England. [Davis, Stephen] Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Melbourne, Vic 3050, Australia. [Diener, Hans-Christoph] Univ Duisburg Essen, Dept Neurol, Essen, Germany. [Fisher, Marc] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. [Hacke, Werner] Heidelberg Univ, Dept Neurol, Heidelberg, Germany. [Hanley, Daniel F.] Johns Hopkins Med Inst, Div Brain Injury Outcomes, Baltimore, MD 21205 USA. [Luby, Marie; Warach, Steven] NINDS, Stroke Diagnost & Therapeut Sect, Bethesda, MD 20892 USA. [Tsivgoulis, G.] Democritus Univ Thrace, Dept Neurol, Alexandroupolis, Greece. [Wahlgren, Nils] Karolinska Hosp, Dept Clin Neurosci, S-10401 Stockholm, Sweden. [Ali, Myzoon; Lees, Kennedy R.] Univ Glasgow, Western Infirm, Inst Cardiovasc Med Sci, Glasgow G11 6NT, Lanark, Scotland. RP Ali, M (reprint author), Glasgow Caledonian Univ, NMAHP Res Unit, Cowcaddens Rd, Glasgow G4 0BA, Lanark, Scotland. EM vista.collaboration@glasgow.ac.uk RI Davis, Stephen/L-5260-2013; Tyson, Sarah/J-3874-2014; OI Davis, Stephen/0000-0003-0962-2300; Tyson, Sarah/0000-0001-6301-8791; Bowen, Audrey/0000-0003-4075-1215; Stibrant Sunnerhagen, Katharina/0000-0002-5940-4400; Drummond, Avril/0000-0003-1220-8354; Bath, Philip/0000-0003-2734-5132; Gregson, Barbara/0000-0003-4868-9137; Donnan, Geoffrey/0000-0001-6324-3403; Pollock, Alex/0000-0003-4941-7985; Logan, Philippa/0000-0002-6657-2381; Kaste, Markku/0000-0001-6557-6412 FU Chief Scientist Office (CSO) Scottish Government's Health Directorate, Scotland FX Funding: VISTA is a not-for-profit collaboration of researchers from academia and commercial organizations. The VISTA Steering Committee members have each contributed to the organization of contributing trials, and where these have involved industry support, they have acknowledged that within the original publications. No author has any additional conflict of interest to declare in relation to this work, which was not externally supported. MA, MB, and the Nursing, Midwifery and Allied Health Professions Research Unit are funded by the Chief Scientist Office (CSO) Scottish Government's Health Directorate, Scotland. NR 20 TC 37 Z9 37 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD FEB PY 2012 VL 7 IS 2 BP 133 EP 138 DI 10.1111/j.1747-4949.2011.00735.x PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 879MS UT WOS:000299334600006 PM 22264365 ER PT J AU Yin, J Yan, XD Yao, X Zhang, YL Shan, Y Mao, N Yang, YL Pan, LY AF Yin, Jie Yan, Xuedong Yao, Xin Zhang, Yongli Shan, Ying Mao, Ning Yang, Yili Pan, Lingya TI Secretion of annexin A3 from ovarian cancer cells and its association with platinum resistance in ovarian cancer patients SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE annexin A3; ovarian cancer; platinum; drug resistance; biomarker ID BRUSH-BORDER MEMBRANE; ELECTRON-MICROSCOPY; EXPRESSION; CISPLATIN; CARCINOMA; PROTEIN; IV AB Early detection of resistance to platinum-based therapy is critical for improving the treatment of ovarian cancers. We have previously found that increased expression of annexin A3 is a mechanism for platinum resistance in ovarian cancer cells. Here we demonstrate that annexin A3 can be detected in the culture medium of ovarian cancer cells, particularly these cells that express high levels of annexin A3. Levels of annexin A3 were then determined in sera from ovarian cancer patients using an enzyme-linked immunosorbent assay. Compared with those from normal donors, sera from ovarian cancer patients contain significantly higher levels of annexin A3. Furthermore, serum levels of annexin A3 were significantly higher in platinum-resistant patients than in platinum-sensitive patients. To gain insight into the mechanism of secretion, the ovarian cancer cell lines were examined using both transmission electron microscopy and immunoelectron microscopy. Compared with parent cells, there are significantly more vesicles in the cytoplasm of ovarian cancer cells that express high levels of annexin A3, and at least some vesicles are annexin A3-positive. Moreover, some vesicles appear to be fused with the cell membrane, suggesting that annexin A3 secretion may be associated with exocytosis and the release of exosomes. This is supported by our observation that ovarian cancer cells expressing higher levels of annexin A3 released increased numbers of exosomes. Furthermore, annexin A3 can be detected in exosomes released from cisplatin-resistant cells (SKOV3/Cis) by immunoblotting and immunoelectron microscopy. C1 [Yin, Jie; Yan, Xuedong; Yao, Xin; Zhang, Yongli; Shan, Ying; Pan, Lingya] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Obstet & Gynecol, Beijing 100730, Peoples R China. [Yin, Jie; Yan, Xuedong; Yao, Xin; Zhang, Yongli; Shan, Ying; Pan, Lingya] Peking Union Med Coll, Beijing 100730, Peoples R China. [Mao, Ning] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Cell Biol, Beijing 100730, Peoples R China. [Yang, Yili] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA. RP Pan, LY (reprint author), Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Obstet & Gynecol, 1 Shuai Fu Yuan,Wang Fu Jing St, Beijing 100730, Peoples R China. EM lingyapan@hotmail.com FU Key Foundation of PUMC Hospital [200203]; Department of Cell Biology, Institute of Basic Medical Sciences FX This work was supported by the Key Foundation of PUMC Hospital (Grant 200203). We thank Dr. Joel D. Ernst (University of California, San Francisco, USA) for anti-annexin A3 antibody, Professor Wei Dai (Electron Microscopy Center, Peking Union Medical College, Beijing, China) for technical assistance in electron microscopy. We are also grateful to our colleagues in the Department of Cell Biology, Institute of Basic Medical Sciences, for their support and technical assistance, and to Dr. Alan O. Perantoni for his editing of the paper. NR 37 TC 26 Z9 30 U1 2 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD FEB PY 2012 VL 16 IS 2 BP 337 EP 348 DI 10.1111/j.1582-4934.2011.01316.x PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 883KU UT WOS:000299633700013 PM 21435174 ER PT J AU Ehler, M AF Ehler, M. TI Random Tight Frames SO JOURNAL OF FOURIER ANALYSIS AND APPLICATIONS LA English DT Article DE Frames; Probability; Optimal configurations ID BI-FRAMES; EXPANSIONS; ERASURES AB We introduce probabilistic frames to study finite frames whose elements are chosen at random. While finite tight frames generalize orthonormal bases by allowing redundancy, independent, uniformly distributed points on the sphere approximately form a finite unit norm tight frame (FUNTF). In the present paper, we develop probabilistic versions of tight frames and FUNTFs to significantly weaken the requirements on the random choice of points to obtain an approximate finite tight frame. Namely, points can be chosen from any probabilistic tight frame, they do not have to be identically distributed, nor have unit norm. We also observe that classes of random matrices used in compressed sensing are induced by probabilistic tight frames. C1 [Ehler, M.] NICHHD, Sect Med Biophys, NIH, Bethesda, MD 20892 USA. [Ehler, M.] Univ Maryland, Norbert Wiener Ctr, Dept Math, College Pk, MD 20742 USA. RP Ehler, M (reprint author), NICHHD, Sect Med Biophys, NIH, Bethesda, MD 20892 USA. EM ehlermar@mail.nih.gov FU National Institute of Child Health and Human Development; NIH/DFG [EH 405/1-1/575910] FX The author was supported by the Intramural Research Program of the National Institute of Child Health and Human Development and by NIH/DFG Research Career Transition Awards Program (EH 405/1-1/575910). The author would also like to thank the anonymous referees for detailed comments and suggestions. NR 27 TC 8 Z9 8 U1 2 U2 10 PU BIRKHAUSER BOSTON INC PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 USA SN 1069-5869 J9 J FOURIER ANAL APPL JI J. Fourier Anal. Appl. PD FEB PY 2012 VL 18 IS 1 BP 1 EP 20 DI 10.1007/s00041-011-9182-5 PG 20 WC Mathematics, Applied SC Mathematics GA 881XL UT WOS:000299525200001 ER PT J AU Goswami, R Jabeen, R Yagi, R Pham, D Zhu, JF Goenka, S Kaplan, MH AF Goswami, Ritobrata Jabeen, Rukhsana Yagi, Ryoji Duy Pham Zhu, Jinfang Goenka, Shreevrat Kaplan, Mark H. TI STAT6-Dependent Regulation of Th9 Development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-3; CD4(+) T-CELLS; C-MAF; SIGNAL TRANSDUCER; GENE-EXPRESSION; HELPER-CELLS; TGF-BETA; DIFFERENTIATION; STAT6; IL-4 AB Th cell effector subsets develop in response to specific cytokine environments. The development of a particular cytokine-secreting pattern requires an integration of signals that may promote the development of opposing pathways. A recent example of this paradigm is the IL-9-secreting Th9 cell that develops in response to TGF-beta and IL-4, cytokines that, in isolation, promote the development of inducible regulatory T cells and Th2 cells, respectively. To determine how the balance of these factors results in priming for IL-9 secretion, we examined the effects of each pathway on transcription factors that regulate Th cell differentiation. We demonstrated that TGF-beta induces the PU.1-encoding Sfpi1 locus and that this is independent of IL-4-induced STAT6 activation. IL-4-activated STAT6 is required for repressing the expression of T-bet and Foxp3 in Th9 cells, transcription factors that inhibit IL-9 production, and STAT6 is required for the induction of IRF4, which promotes Th9 development. These data established a transcription factor network that regulates IL-9 and demonstrated how combinations of cytokine signals generate cytokine-secreting potential by altering the expression of a panel of transcription factors. The Journal of Immunology, 2012, 188: 968-975. C1 [Goswami, Ritobrata; Jabeen, Rukhsana; Duy Pham; Goenka, Shreevrat; Kaplan, Mark H.] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Dept Pediat, Indianapolis, IN 46202 USA. [Goswami, Ritobrata; Duy Pham; Goenka, Shreevrat; Kaplan, Mark H.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Yagi, Ryoji; Zhu, Jinfang] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Kaplan, MH (reprint author), Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Dept Pediat, 1044 W Walnut St,Room 202, Indianapolis, IN 46202 USA. EM mkaplan2@iupui.edu RI Zhu, Jinfang/B-7574-2012; OI Kaplan, Mark/0000-0002-2923-8245 FU Public Health Service [AI057459, HL093105]; Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, the National Institutes of Health FX This work was supported by Public Health Service Grants AI057459 (to M. H. K.) and HL093105 (to S. G.). Y.R. and J.Z. were supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, the National Institutes of Health. NR 39 TC 78 Z9 85 U1 0 U2 17 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 968 EP 975 DI 10.4049/jimmunol.1102840 PG 8 WC Immunology SC Immunology GA 884FL UT WOS:000299690200009 PM 22180613 ER PT J AU Janbazian, L Price, DA Canderan, G Filali-Mouhim, A Asher, TE Ambrozak, DR Scheinberg, P Boulassel, MR Routy, JP Koup, RA Douek, DC Sekaly, RP Trautmann, L AF Janbazian, Loury Price, David A. Canderan, Glenda Filali-Mouhim, Abdelali Asher, Tedi E. Ambrozak, David R. Scheinberg, Phillip Boulassel, Mohamad Rachid Routy, Jean-Pierre Koup, Richard A. Douek, Daniel C. Sekaly, Rafick-Pierre Trautmann, Lydie TI Clonotype and Repertoire Changes Drive the Functional Improvement of HIV-Specific CD8 T Cell Populations under Conditions of Limited Antigenic Stimulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; PD-1 EXPRESSION; HIGH-AVIDITY; IN-VIVO; HUMAN CYTOMEGALOVIRUS; VIRAL PERSISTENCE; LYMPHOCYTE ESCAPE; TYPE-1 INFECTION AB Persistent exposure to cognate Ag leads to the functional impairment and exhaustion of HIV-specific CD8 T cells. Ag withdrawal, attributable either to antiretroviral treatment or the emergence of epitope escape mutations, causes HIV-specific CD8 T cell responses to wane over time. However, this process does not continue to extinction, and residual CD8 T cells likely play an important role in the control of HIV replication. In this study, we conducted a longitudinal analysis of clonality, phenotype, and function to define the characteristics of HIV-specific CD8 T cell populations that persist under conditions of limited antigenic stimulation. Ag decay was associated with dynamic changes in the TCR repertoire, increased expression of CD45RA and CD127, decreased expression of programmed death-1, and the emergence of polyfunctional HIV-specific CD8 T cells. High-definition analysis of individual clonotypes revealed that the Ag loss-induced gain of function within HIV-specific CD8 T cell populations could be attributed to two nonexclusive mechanisms: 1) functional improvement of persisting clonotypes; and 2) recruitment of particular clonotypes endowed with superior functional capabilities. The Journal of Immunology, 2012, 188: 1156-1167. C1 [Canderan, Glenda; Sekaly, Rafick-Pierre; Trautmann, Lydie] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL 34987 USA. [Janbazian, Loury; Filali-Mouhim, Abdelali; Sekaly, Rafick-Pierre] Univ Montreal, Dept Microbiol & Immunol, Immunol Lab, Montreal, PQ H2X 1P1, Canada. [Price, David A.; Asher, Tedi E.; Ambrozak, David R.; Scheinberg, Phillip; Koup, Richard A.; Douek, Daniel C.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Sekaly, Rafick-Pierre; Trautmann, Lydie] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales. [Boulassel, Mohamad Rachid; Routy, Jean-Pierre] McGill Univ, Ctr Hlth, Royal Victoria Hosp, Div Hematol, Montreal, PQ H3A 1A1, Canada. [Sekaly, Rafick-Pierre] McGill Univ, Dept Microbiol & Immunol, Fac Med, Montreal, PQ H3A 2B4, Canada. [Sekaly, Rafick-Pierre; Trautmann, Lydie] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA. RP Trautmann, L (reprint author), Vaccine & Gene Therapy Inst Florida, 11350 SW Village Pkwy, Port St Lucie, FL 34987 USA. EM ltrautmann@vgtifl.org RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Scheinberg, Phillip/0000-0002-9047-4538 FU Canadian Institutes for Health Research; Fonds de la Recherche en Sante du Quebec Reseau Sida et Maladies Infectieuses; National Institutes of Health [IDPIDA028871-01]; Office of Tourism, Trade, and Economic Development of Florida FX This work was supported by funds from the Canadian Institutes for Health Research, the Fonds de la Recherche en Sante du Quebec Reseau Sida et Maladies Infectieuses, the National Institutes of Health (Grant IDPIDA028871-01), and the Office of Tourism, Trade, and Economic Development of Florida. D.A.P. is a Medical Research Council (U.K.) Senior Clinical Fellow. NR 65 TC 19 Z9 19 U1 0 U2 3 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 1156 EP 1167 DI 10.4049/jimmunol.1102610 PG 12 WC Immunology SC Immunology GA 884FL UT WOS:000299690200030 PM 22210916 ER PT J AU Baranova, IN Vishnyakova, TG Bocharov, AV Leelahavanichkul, A Kurlander, R Chen, ZG Souza, ACP Yuen, PST Star, RA Csako, G Patterson, AP Eggerman, TL AF Baranova, Irina N. Vishnyakova, Tatyana G. Bocharov, Alexander V. Leelahavanichkul, Asada Kurlander, Roger Chen, Zhigang Souza, Ana C. P. Yuen, Peter S. T. Star, Robert A. Csako, Gyorgy Patterson, Amy P. Eggerman, Thomas L. TI Class B Scavenger Receptor Types I and II and CD36 Mediate Bacterial Recognition and Proinflammatory Signaling Induced by Escherichia coli, Lipopolysaccharide, and Cytosolic Chaperonin 60 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; ATHEROSCLEROTIC LESION DEVELOPMENT; HEAT-SHOCK PROTEINS; SMOOTH-MUSCLE-CELLS; INNATE IMMUNE CELLS; ENDOTHELIAL-CELLS; DENDRITIC CELLS; HUMAN MONOCYTES; GLUCOCORTICOID PRODUCTION; INFLAMMATORY RESPONSES AB Class B scavenger receptors (SR-B) are lipoprotein receptors that also mediate pathogen recognition, phagocytosis, and clearance as well as pathogen-induced signaling. In this study we report that three members of the SR-B family, namely, CLA-1, CLA-2, and CD36, mediate recognition of bacteria not only through interaction with cell wall LPS but also with cytosolic chaperonin 60. HeLa cells stably transfected with any of these SR-Bs demonstrated markedly (3- to 5-fold) increased binding and endocytosis of Escherichia coli, LPS, and chaperonin 60 (GroEL) as revealed by both FACS analysis and confocal microscopy imaging. Increased pathogen (E. coli, LPS, and GroEL) binding to SR-Bs was also associated with the dose-dependent stimulation of cytokine secretion in the order of CD36 > CLA-2 > CLA-1 in HEK293 cells. Pathogen-induced IL-6-secretion was reduced in macrophages from CD36- and SR-BI/II-null mice by 40-50 and 30-40%, respectively. Intravenous GroEL administration increased plasma IL-6 and CXCL1 levels in mice. The cytokine responses were 40-60% lower in CD36(-/-) relative to wild-type mice, whereas increased cytokine responses were found in SR-BI/II-/- mice. While investigating the discrepancy of in vitro versus in vivo data in SR-BI/II deficiency, SR-BI/II-/- mice were found to respond to GroEL administration without increases in either plasma corticosterone or aldosterone as normally seen in wild-type mice. SR-BI/II-/- mice with mineralocorticoid replacement demonstrated an similar to 40-50% reduction in CXCL1 and IL-6 responses. These results demonstrate that, by recognizing and mediating inflammatory signaling of both bacterial cell wall LPS and cytosolic GroEL, all three SR-B family members play important roles in innate immunity and host defense. The Journal of Immunology, 2012, 188: 1371-1380. C1 [Eggerman, Thomas L.] NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. [Baranova, Irina N.; Vishnyakova, Tatyana G.; Bocharov, Alexander V.; Kurlander, Roger; Chen, Zhigang; Csako, Gyorgy; Patterson, Amy P.; Eggerman, Thomas L.] NIDDKD, Dept Lab Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Leelahavanichkul, Asada; Souza, Ana C. P.; Yuen, Peter S. T.; Star, Robert A.] NIDDKD, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. [Leelahavanichkul, Asada] Chulalongkorn Univ, Fac Med, Dept Microbiol, Bangkok 10330, Thailand. [Patterson, Amy P.] NIH, Off Biotechnol Activ, Off Director, Bethesda, MD 20892 USA. RP Eggerman, TL (reprint author), NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, 6707 Democracy Blvd,Room 697,MSC 5460, Bethesda, MD 20892 USA. EM abocharov@cc.nih.gov; Eggermant@niddk.nih.gov RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 FU Clinical Center, National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the Clinical Center, National Institute of Diabetes and Digestive and Kidney Diseases, and by the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 70 TC 36 Z9 39 U1 0 U2 3 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 1371 EP 1380 DI 10.4049/jimmunol.1100350 PG 10 WC Immunology SC Immunology GA 884FL UT WOS:000299690200052 PM 22205027 ER PT J AU Crampton, SP Deane, JA Feigenbaum, L Bolland, S AF Crampton, Steve P. Deane, Jonathan A. Feigenbaum, Lionel Bolland, Silvia TI Ifih1 Gene Dose Effect Reveals MDA5-Mediated Chronic Type I IFN Gene Signature, Viral Resistance, and Accelerated Autoimmunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; BLOOD MONONUCLEAR-CELLS; CHRONIC DISEASE; IMMUNE-SYSTEM; INTERFERON; EXPRESSION; MICE; RESPONSES; RECEPTOR; ANEMIA AB Type I IFNs (IFN-I) are normally produced during antiviral responses, yet high levels of chronic IFN-I expression correlate with autoimmune disease. A variety of viral sensors generate IFN-I in their response, but other than TLRs, it is not fully known which pathways are directly involved in the development of spontaneous immune pathologies. To further explore the link between IFN-I induced by viral pathways and autoimmunity, we generated a new transgenic mouse line containing multiple copies of Ifih1, a gene encoding the cytoplasmic dsRNA sensor MDA5 with proven linkage to diabetes and lupus. We show that MDA5 overexpression led to a chronic IFN-I state characterized by resistance to a lethal viral infection through rapid clearance of virus in the absence of a CD8(+) or Ab response. Spontaneous MDA5 activation was not sufficient to initiate autoimmune or inflammatory pathology by itself, even though every immune cell population had signs of IFN activation. When combined with the lupus-susceptible background of the Fc gamma R2B deficiency, MDA5 overexpression did accelerate the production of switched autoantibodies, the incidence of glomerulonephritis, and early lethality. Thus, MDA5 transgenic mice provide evidence that chronic elevated levels of IFN-I are not sufficient to initiate autoimmunity or inflammation although they might exacerbate an ongoing autoimmune pathology. The Journal of Immunology, 2012, 188: 1451-1459. C1 [Crampton, Steve P.; Bolland, Silvia] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Deane, Jonathan A.] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. [Feigenbaum, Lionel] NCI, NIH, Frederick, MD 21702 USA. RP Bolland, S (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr,Room 217,MSC 8180, Rockville, MD 20852 USA. EM sbolland@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 45 TC 35 Z9 36 U1 3 U2 6 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 1451 EP 1459 DI 10.4049/jimmunol.1102705 PG 9 WC Immunology SC Immunology GA 884FL UT WOS:000299690200060 PM 22205024 ER PT J AU Calamusa, G Valenti, RM Vitale, F Mammina, C Romano, N Goedert, JJ Gori-Savellini, G Cusi, MG Amodio, E AF Calamusa, Giuseppe Valenti, Rosalia Maria Vitale, Francesco Mammina, Caterina Romano, Nino Goedert, James Jerome Gori-Savellini, Gianni Cusi, Maria Grazia Amodio, Emanuele TI Seroprevalence of and risk factors for Toscana and Sicilian virus infection in a sample population of Sicily (Italy) SO JOURNAL OF INFECTION LA English DT Article DE Toscana virus; Sicilian virus; Re-emergence; Italy ID ACUTE MENINGITIS; PHLEBOVIRUS; PREVALENCE AB Objective: The present study aimed to assess seroprevalence of and risk factors for Toscana (TOSV) and Sicilian (SFSV) virus infections in a sample of Sicilian subjects. Methods: A cross-sectional seroepidemiological study was conducted on 271 individuals. Each participant completed a self-administrated questionnaire and provided a serum sample which was analyzed for the presence of IgG specific anti-TOSV and anti-SFSV viruses. Results: Overall, 90 subjects (33.2%) were positive for TOSV IgG, 25 (9.2%) were positive for SFSV IgG and 11 (4%) were positive for both the viruses. A higher risk for TOSV seropositivity was found in participants who were older (adjOR = 1.02 per year; 95% CI=1.01-1.03), having a pet living outdoors (adjOR = 2.62; 95% CI = 1.42-4.83) and being obese (adjOR = 2.37; 95% CI = 1.06-5.30). Conclusions: TOSV seroprevalence appears to be relatively high in Sicilian general population, especially in older adults, representing a potential public health concern. The observations that seropositivity for TOSV was not significantly associated with SFSV seropositivity, and none of the risk factors associated with TOSV were associated with SFSV seem to suggest that these two phleboviruses may have different ecology and transmission pathways. (C) 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved. C1 [Calamusa, Giuseppe; Valenti, Rosalia Maria; Vitale, Francesco; Mammina, Caterina; Romano, Nino; Amodio, Emanuele] Univ Palermo, Dept Sci Hlth Promot G DAlessandro, I-90127 Cap, Italy. [Goedert, James Jerome] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Gori-Savellini, Gianni; Cusi, Maria Grazia] Univ Siena, Dept Mol Biol, Microbiol Sect, I-53100 Siena, Italy. RP Amodio, E (reprint author), Univ Palermo, Dept Sci Hlth Promot G DAlessandro, Via Vespro 133, I-90127 Cap, Italy. EM emanuele.amodio@unipa.it RI Mammina, Caterina/M-9339-2013; OI Gori Savellini, Gianni/0000-0003-2287-9258; Mammina, Caterina/0000-0003-2881-8018 FU Intramural NIH HHS [ZIA CP010214-01] NR 25 TC 5 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 J9 J INFECTION JI J. Infect. PD FEB PY 2012 VL 64 IS 2 BP 212 EP 217 DI 10.1016/j.jinf.2011.11.012 PG 6 WC Infectious Diseases SC Infectious Diseases GA 879EP UT WOS:000299312800011 PM 22120113 ER PT J AU Patel, GK Yee, CL Yuspa, SH Vogel, JC AF Patel, Girish K. Yee, Carole L. Yuspa, Stuart H. Vogel, Jonathan C. TI A Humanized Stromal Bed Is Required for Engraftment of Isolated Human Primary Squamous Cell Carcinoma Cells in Immunocompromised Mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID NONMELANOMA SKIN-CANCER; SCID MICE; KAPPA-B; MOUSE; INFLAMMATION; PROGRESSION; POPULATION; TISSUE; P53 AB Epithelial cancers are the most common malignancies and the greatest cause of cancer mortality worldwide. The incidence of keratinocyte-derived (non-melanoma) skin cancers is increasing rapidly. Despite access to abundant tumor tissue and ease of observation, acceptance of non-melanoma skin cancers as model carcinomas has been hindered by the lack of a reliable xenograft model. Herein we describe conditions that allow routine xeno-engraftment of primary human squamous cell carcinoma (SCCa) cells. Tumor development required creation of an appropriate stromal bed before xenografting tumor tissue onto the backs of athymic nude mice. We also demonstrate that the stromal bed must be "humanized" if primary human SCCa is to be propagated from cell suspensions. SCCa xenografts recapitulated the histological grade and phenotype of the original tumors with considerable fidelity, even after serial passage, irrespective of the histological grade of the primary human SCCa. This model, which to our knowledge is previously unreported, can be used for drug testing, as well as for studies that are relevant to the biology of primary human SCCa and other epithelial cancers. C1 [Patel, Girish K.; Yee, Carole L.; Vogel, Jonathan C.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Patel, GK (reprint author), Cardiff Univ, Sch Med, Dept Dermatol & Wound Healing, Heath Pk, Cardiff CF14 4XN, S Glam, Wales. EM patelgk@cardiff.ac.uk RI Patel, Girish/N-7075-2013 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank all the members of the Dermatology Branch (National Cancer Institute, NIH, Bethesda, Maryland), including Dr Mark Udey for many helpful discussions and comments and, in particular, Vogel laboratory members for their helpful comments. We thank Drs Andrew Montemarano (Rockledge Skin Cancer Clinic, Bethesda, Maryland), Kurt Maggio (Walter Reed Army Medical Center Dermatology Service, Washington, DC), and Martin Braun (Braun & Braun MDs, Washington, DC) for providing tumor tissue samples. It is with great sadness that we also inform you of the recent and untimely death of Dr Jonathan C Vogel, the lead principal investigator of this paper. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 30 TC 12 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2012 VL 132 IS 2 BP 284 EP 290 DI 10.1038/jid.2011.284 PG 7 WC Dermatology SC Dermatology GA 877XH UT WOS:000299215500007 PM 21975825 ER PT J AU Patel, GK Yee, CL Terunuma, A Telford, WG Voong, N Yuspa, SH Vogel, JC AF Patel, Girish K. Yee, Carole L. Terunuma, Atsushi Telford, William G. Voong, Nga Yuspa, Stuart H. Vogel, Jonathan C. TI Identification and Characterization of Tumor-Initiating Cells in Human Primary Cutaneous Squamous Cell Carcinoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CANCER STEM-CELLS; SKIN-CANCER; INVOLUCRIN EXPRESSION; CD133; PROGRESSION; POPULATION; MARKER; P53 AB Primary human squamous cell carcinomas (SCCas) are heterogeneous invasive tumors with proliferating outer layers and inner differentiating cell masses. To determine if tumor-initiating cells (TICs) are present in SCCas, we utilized newly developed reliable in vitro and in vivo xenograft assays that propagate human SCCas, and demonstrated that a small subset of SCCa cells (similar to 1%) expressing Prominin-1 (CD133) in the outer layers of SCCas were highly enriched for TICs (similar to 1/400) compared with unsorted SCCa cells (TICs similar to 1/10(6)). Xenografts of CD133+ SCCas recreated the original SCCa tumor histology and organizational hierarchy, whereas CD133- cells did not, and only CD133+ cells demonstrated the capacity for self-renewal in serial transplantation studies. We present a model of human SCCas in which tumor projections expand with outer leading edges that contain CD133+ TICs. Successful cancer treatment will likely require that the TICs identified in cancers be targeted therapeutically. The demonstration that TICs are present in SCCas and are enriched in a CD133- expressing subpopulation has not been, to our knowledge, previously reported. C1 [Patel, Girish K.; Yee, Carole L.; Terunuma, Atsushi; Vogel, Jonathan C.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Telford, William G.; Voong, Nga] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Patel, GK (reprint author), Cardiff Univ, Sch Med, Dept Dermatol & Wound Healing, Heath Pk, Cardiff CF14 4XN, S Glam, Wales. EM patelgk@cardiff.ac.uk RI Patel, Girish/N-7075-2013 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank all members of the Dermatology Branch (National Cancer Institute, NIH, Bethesda, Maryland), including Dr Mark Udey, for many helpful discussions and comments, and in particular Vogel laboratory members for their helpful comments. We thank Ms Rachelle Graham for undertaking immunohistochemical characterization of SCCas. Also, we thank Drs Andrew Montemarano (Rockledge Skin Cancer Clinic, Bethesda, Maryland), Kurt Maggio (Walter Reed Army Medical Center Dermatology Service, Washington, DC), and Martin Braun (Braun & Braun MDs, Washington, DC) for providing tumor tissue samples. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 26 TC 22 Z9 22 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 401 EP 409 DI 10.1038/jid.2011.317 PG 9 WC Dermatology SC Dermatology GA 877XH UT WOS:000299215500021 PM 22011906 ER PT J AU Law, MH Montgomery, GW Brown, KM Martin, NG Mann, GJ Hayward, NK MacGregor, S AF Law, Matthew H. Montgomery, Grant W. Brown, Kevin M. Martin, Nicholas G. Mann, Graham J. Hayward, Nicholas K. MacGregor, Stuart CA Q-MEGA & AMFS Investigators TI Meta-Analysis Combining New and Existing Data Sets Confirms that the TERT-CLPTM1L Locus Influences Melanoma Risk SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID GENOME-WIDE ASSOCIATION; TELOMERE LENGTH; CANCER-RISK; SUSCEPTIBILITY; VARIANTS; SEQUENCE; DESIGN; CELLS; TERT; LINE C1 [Law, Matthew H.; Montgomery, Grant W.; Martin, Nicholas G.; Hayward, Nicholas K.; MacGregor, Stuart] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Brown, Kevin M.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Mann, Graham J.] Univ Sydney, Westmead Inst Canc Res, Millennium Inst, Westmead, NSW 2145, Australia. [Mann, Graham J.] Melanoma Inst Australia, Westmead, NSW, Australia. RP Law, MH (reprint author), Queensland Inst Med Res, Brisbane, Qld 4006, Australia. EM matthew.law@qimr.edu.au RI Macgregor, Stuart/C-6442-2009; Stark, Mitchell/E-3542-2010; Mann, Graham/G-4758-2014; hayward, nicholas/C-1367-2015; Montgomery, Grant/B-7148-2008; Duffy, David/B-7392-2013 OI Gruis, Nelleke/0000-0002-5210-9150; Macgregor, Stuart/0000-0001-6731-8142; Stark, Mitchell/0000-0002-4510-2161; Puig, Susana/0000-0003-1337-9745; Martin, Nicholas/0000-0003-4069-8020; Mann, Graham/0000-0003-1301-405X; hayward, nicholas/0000-0003-4760-1033; Montgomery, Grant/0000-0002-4140-8139; Duffy, David/0000-0001-7227-632X FU NCI NIH HHS [R01 CA122838-03, P01 CA055075, P01 CA055075-17, P01 CA087969, P01 CA087969-12, R01 CA049449, R01 CA049449-14, R01 CA083115, R01 CA083115-10, R01 CA088363, R01 CA088363-10, R01 CA100264, R01 CA100264-05, R01 CA122838, R01 CA133996, R01 CA133996-03, U01 CA049449, U19 CA148127] NR 17 TC 26 Z9 26 U1 0 U2 4 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 485 EP 487 DI 10.1038/jid.2011.322 PG 4 WC Dermatology SC Dermatology GA 877XH UT WOS:000299215500036 PM 21993562 ER PT J AU Mehta, GU Lonser, RR Oldfield, EH AF Mehta, Gautam U. Lonser, Russell R. Oldfield, Edward H. TI The history of pituitary surgery for Cushing disease SO JOURNAL OF NEUROSURGERY LA English DT Article DE Cushing disease; Harvey Cushing; history; pituitary adenoma; transsphenoidal surgery ID TRANSSPHENOIDAL REMOVAL; BASOPHILISM; HYPOPHYSIS; HYPOTHALAMUS; MICROADENOMA; ADENOMA; TUMORS; GLAND AB Although he never performed a pituitary operation for the disease, Harvey Cushing was the first to describe and treat patients with Cushing disease (CD). Other surgeons at the time were reluctant to operate on the pituitary due to the normal sella on skull radiographs in CD and the unclear etiology of the disorder. To better define and understand factors influencing the history of pituitary surgery for CD, the authors analyzed historical texts related to CD biology, diagnosis, and treatment. Cushing's monograph on basophilic pituitary adenomas and cortisol excess appeared in 1932. One year later in 1933, Alfred Pattison performed the first successful pituitary operation for CD by implanting radon seeds in the sella. Resection of a pituitary adenoma for CD was attempted 1 month later in 1933 by Howard Naffziger, resulting in only transient improvement that corresponded to the lack of tumor in the resected tissue. Soon thereafter, Susman in 1935 and Costello in 1936 described pituitary basophilic adenomas at autopsy in patients without premorbid endocrinopathy. They concluded that the adrenal gland was the cause of CD, which resulted in a 3-decade abandonment of pituitary surgery for CD. Jules Hardy in 1963 used the operating microscope to perform the first selective removal of an adrenocorticotropic hormone (ACTH) secreting microadenoma, which established a pituitary cause and defined the modern treatment of CD. Subsequent reports by Hardy. Laws, and Wilson resulted in widespread acceptance of pituitary surgery for CD. Initial reluctance to operate on the pituitary for CD was multifaceted and included general uncertainty surrounding the etiology of Cushing syndrome as well as a lack of early surgical success, both due to the small size of ACTH-secreting adenomas. Selective removal of ACTH-secreting adenomas identified the source of CD and ended the delay in acceptance of pituitary surgery for CD. (DOI: 10.3171/2011.8.JNS102005) C1 [Mehta, Gautam U.; Oldfield, Edward H.] Univ Virginia, Dept Neurosurg, Univ Virginia Hlth Syst, Charlottesville, VA 22901 USA. [Mehta, Gautam U.; Lonser, Russell R.; Oldfield, Edward H.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), Univ Virginia, Dept Neurosurg, Univ Virginia Hlth Syst, Charlottesville, VA 22901 USA. EM eho4u@hscmail.mcc.virginia.edu OI Mehta, Gautam/0000-0002-8009-6430 NR 43 TC 7 Z9 8 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2012 VL 116 IS 2 BP 261 EP 268 DI 10.3171/2011.8.JNS102005 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 882SB UT WOS:000299583100001 PM 21962161 ER PT J AU Lonser, RR Oldfield, EH AF Lonser, Russell R. Oldfield, Edward H. TI Invasion of the corticotrophs Response SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID PITUITARY-ADENOMAS; DURAL INVASION; PSEUDOCAPSULE; SURGERY C1 [Lonser, Russell R.; Oldfield, Edward H.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Oldfield, Edward H.] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2012 VL 116 IS 2 BP 270 EP 271 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 882SB UT WOS:000299583100003 ER PT J AU Lonser, RR Ksendzovsky, A Wind, JJ Vortmeyer, AO Oldfield, EH AF Lonser, Russell R. Ksendzovsky, Alexander Wind, Joshua J. Vortmeyer, Alexander O. Oldfield, Edward H. TI Prospective evaluation of the characteristics and incidence of adenoma-associated dural invasion in Cushing disease SO JOURNAL OF NEUROSURGERY LA English DT Article DE adenoma; cavernous sinus; Cushing disease; dura; invasion; pituitary surgery ID PITUITARY-ADENOMAS; SURGERY; TUMORS; CLASSIFICATION; PERSISTENT; DIAGNOSIS; CHILDREN AB Object. Dural invasion by adrenocorticotropic hormone (ACTH)-secreting adenomas is a significant risk factor for incomplete resection and recurrence in Cushing disease (CD). Since ACTH-producing adenomas are often the smallest of the various types of pituitary tumors at the time of resection, examining their invasion provides the best opportunity to identify the precise sites of early dural invasion by pituitary adenomas. To characterize the incidence and anatomical distribution of dural invasion by ACTH-secreting adenomas, the authors prospectively and systematically analyzed features of dural invasion in patients with CD. Methods. The authors prospectively studied consecutive patients with CD undergoing the systematic removal of ACTH-secreting adenoma and histological analysis of the anterior sella dura as well as other sites of dural invasion that were evident at surgery. Clinical, imaging, histological, and operative findings were analyzed. Results. Eighty-seven patients with CD (58 females and 29 males) were included in the study. Overall, dural invasion by an ACTH-positive adenoma was histologically confirmed in 30 patients (34%). Eighteen patients (60% of dural invasion cases, 21% of all patients) had evidence of cavernous sinus wall invasion (4 of these patients also had other contiguous sites of invasion), and 12 patients (40% of dural invasion cases) had invasion of the sella dura excluding the cavernous sinus wall. Eleven patients (13% all patients) had invasion of the routinely procured anterior sella dura specimen. Preoperative MR imaging revealed an adenoma in 64 patients (74%) but accurately predicted dural invasion in only 4 patients (22%) with cavernous sinus invasion and none of the patients with non cavernous sinus invasion. Adenomas associated with dural invasion (mean SD, 10.9 +/- 7.8 mm, range 2-37 mm) were significantly larger than those not associated with dural invasion (5.7 +/- 2.1 mm, range 2.5-12 mm; p = 0.0006, Mann-Whitney test). Conclusions. Dural invasion by ACTH-producing adenomas preferentially occurs laterally into the wall of the cavernous sinus. Preoperative MR imaging infrequently detects dural invasion, including cavernous sinus invasion. Invasion is directly associated with tumor size. To provide a biochemical cure and avoid recurrence after resection, identification and removal of invaded sella dura, including the medial cavernous sinus wall, are necessary. (DOI: 10.3171/2011.8.JNS11456) C1 [Lonser, Russell R.; Ksendzovsky, Alexander; Wind, Joshua J.; Vortmeyer, Alexander O.; Oldfield, Edward H.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Oldfield, Edward H.] Univ Virginia, Dept Neurol Surg, Univ Virginia Hlth Syst, Charlottesville, VA USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Rm 3D20, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov RI Wind, Joshua/D-5480-2013 OI Wind, Joshua/0000-0003-3443-8476 FU National Institute of Neurologic Disorders and Stroke at the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurologic Disorders and Stroke at the National Institutes of Health. NR 23 TC 14 Z9 16 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2012 VL 116 IS 2 BP 272 EP 279 DI 10.3171/2011.8.JNS11456 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 882SB UT WOS:000299583100004 PM 21923247 ER PT J AU Cao, XL Yang, CL Pei, HR Li, XH Xu, XB Ito, Y AF Cao, Xueli Yang, Chunlei Pei, Hairun Li, Xinghong Xu, Xiaobai Ito, Yoichiro TI Application of counter-current chromatography as a new pretreatment method for the determination of polycyclic aromatic hydrocarbons in environmental water SO JOURNAL OF SEPARATION SCIENCE LA English DT Article DE Counter-current chromatography (CCC); Enrichment and cleanup; Environmental water; Polycyclic aromatic hydrocarbons (PAHs); Pretreatment ID LIQUID-LIQUID-EXTRACTION; SOLID-PHASE EXTRACTION; SAMPLES; PESTICIDES; SEPARATION AB Counter-current chromatography (CCC) was investigated as a new sample pretreatment method for the determination of trace polycyclic aromatic hydrocarbons (PAHs) in water environmental samples. The experiment was performed with a non-aqueous binary two-phase solvent system composed of n-heptane and acetonitrile. The CCC column was first filled with the upper stationary phase, and then a large volume of water sample was pumped into the column while the CCC column was rotated at 1600?rpm. Finally, the trace amounts of PAHs extracted and enriched in the stationary phase were eluted out by the lower mobile phase and determined by gas chromatographyflame ionization detector (GC-FID) or gas chromatographymass spectrometry (GC-MS). The enrichment and cleanup of PAHs can be fulfilled online by this method with high recoveries (84.1103.2%) and good reproducibility (RSDs: 4.912.2%) for 16 EPA PAHs under the optimized CCC pretreatment conditions. This method has been successfully applied to determine PAHs in lake water where 8 PAHs were detected in the concentration of 40.989.9?ng/L. The present method is extremely suitable for the preparation of large volume of environmental water sample for the determination of trace amounts of organic pollutants including PAHs as studied in this paper. C1 [Cao, Xueli; Yang, Chunlei; Pei, Hairun] Beijing Technol & Business Univ, Sch Food & Chimer Engn, Beijing 100048, Peoples R China. [Li, Xinghong; Xu, Xiaobai] Chinese Acad Sci, Ecoenvironm Sci Res Ctr, State Key Lab Environm Chem & Ecotoxicol, Beijing, Peoples R China. [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Cao, XL (reprint author), Beijing Technol & Business Univ, Sch Food & Chimer Engn, 33 Fucheng Rd, Beijing 100048, Peoples R China. EM caoxl@th.btbu.edu.cn RI Li, Hong/M-3851-2013 FU National Natural Science Foundation of China [20877005]; National High Technology Research and Development Program ("863" Program) [2007AA061601] FX The authors acknowledge the financial support of this work by the National Natural Science Foundation of China (No. 20877005) the National High Technology Research and Development Program ("863" Program No. 2007AA061601). NR 17 TC 3 Z9 4 U1 1 U2 32 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1615-9306 J9 J SEP SCI JI J. Sep. Sci. PD FEB PY 2012 VL 35 IS 4 BP 596 EP 601 DI 10.1002/jssc.201100852 PG 6 WC Chemistry, Analytical SC Chemistry GA 882FL UT WOS:000299548100016 PM 22282420 ER PT J AU Fox, NA Pine, DS AF Fox, Nathan A. Pine, Daniel S. TI Temperament and the Emergence of Anxiety Disorders SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID BEHAVIORAL-INHIBITION; FRAMEWORK C1 [Fox, Nathan A.] Univ Maryland, College Pk, MD 20742 USA. [Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA. RP Fox, NA (reprint author), Univ Maryland, 3304 Benjamin, College Pk, MD 20742 USA. EM fox@umd.edu FU NICHD NIH HHS [R01 HD017899, R37 HD017899, R37HD17899]; NIMH NIH HHS [U01MH093349, R01 MH074454, U01 MH074454, U01 MH093349] NR 12 TC 23 Z9 23 U1 0 U2 7 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 125 EP 128 DI 10.1016/j.jaac.2011.10.006 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 882YD UT WOS:000299598900001 PM 22265356 ER PT J AU Scahill, L McDougle, CJ Aman, MG Johnson, C Handen, B Bearss, K Dziura, J Butter, E Swiezy, NG Arnold, LE Stigler, KA Sukhodolsky, DD Lecavalier, L Pozdol, SL Nikolov, R Hollway, JA Korzekwa, P Gavaletz, A Kohn, AE Koenig, K Grinnon, S Mulick, JA Yu, S Vitiello, B AF Scahill, Lawrence McDougle, Christopher J. Aman, Michael G. Johnson, Cynthia Handen, Benjamin Bearss, Karen Dziura, James Butter, Eric Swiezy, Naomi G. Arnold, L. Eugene Stigler, Kimberly A. Sukhodolsky, Denis D. Lecavalier, Luc Pozdol, Stacie L. Nikolov, Roumen Hollway, Jill A. Korzekwa, Patricia Gavaletz, Allison Kohn, Arlene E. Koenig, Kathleen Grinnon, Stacie Mulick, James A. Yu, Sunkyung Vitiello, Benedetto CA Pediat Psychopharmacology Autism TI Effects of Risperidone and Parent Training on Adaptive Functioning in Children With Pervasive Developmental Disorders and Serious Behavioral Problems SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE risperidone; parent training; pervasive developmental disorders; children; adaptive behavior ID AUTISM-SPECTRUM DISORDERS; PSYCHOSOCIAL INTERVENTIONS; YOUNG-PEOPLE; MEDICATION; INDIVIDUALS; PREVALENCE; COMMUNITY; CHECKLIST; VERSION; TRIAL AB Objective: Children with Pervasive Developmental Disorders (PDDs) have social interaction deficits, delayed communication, and repetitive behaviors as well as impairments in adaptive functioning. Many children actually show a decline in adaptive skills compared with age mates over time. Method: This 24-week, three-site, controlled clinical trial randomized 124 children (4 through 13 years of age) with PDDs and serious behavioral problems to medication alone (MED; n = 49; risperidone 0.5 to 3.5 mg/day; if ineffective, switch to aripiprazole was permitted) or a combination of medication plus parent training (PT) (COMB; n = 75). Parents of children in COMB received an average of 11.4 PT sessions. Standard scores and Age-Equivalent scores on Vineland Adaptive Behavior Scales were the outcome measures of primary interest. Results: Seventeen subjects did not have a post-randomization Vineland assessment. Thus, we used a mixed model with outcome conditioned on the baseline Vineland scores. Both groups showed improvement over the 24-week trial on all Vineland domains. Compared with MED. Vineland Socialization and Adaptive Composite Standard scores showed greater improvement in the COMB group (p = .01 and .05, and effect sizes = 0.35 and 0.22, respectively). On Age Equivalent scores, Socialization and Communication domains showed greater improvement in COMB versus MED (p = .03 and 0.05, and effect sizes = 0.33 and 0.14, respectively). Using logistic regression, children in the COMB group were twice as likely to make at least 6 months' gain (equal to the passage of time) in the Vineland Communication Age Equivalent score compared with MED (p = .02). After controlling for IQ this difference was no longer significant. Conclusion: Reduction of serious maladaptive behavior promotes improvement in adaptive behavior. Medication plus PT shows modest additional benefit over medication alone. Clinical trial registration information-RUPP PI PDD: Drug and Behavioral Therapy for Children With Pervasive Developmental Disorders; http://www.clinicaltrials.gov; NCT00080145. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(2):136-146. C1 [Scahill, Lawrence] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [McDougle, Christopher J.; Swiezy, Naomi G.; Stigler, Kimberly A.; Pozdol, Stacie L.; Korzekwa, Patricia; Kohn, Arlene E.] Indiana Univ, Bloomington, IN 47405 USA. [Aman, Michael G.; Butter, Eric; Arnold, L. Eugene; Lecavalier, Luc; Hollway, Jill A.; Mulick, James A.] Ohio State Univ, Columbus, OH 43210 USA. [Johnson, Cynthia; Handen, Benjamin] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. RP Scahill, L (reprint author), Yale Univ, Ctr Child Study, POB 207900, New Haven, CT 06520 USA. EM Lawrence.scahill@yale.edu OI Sukhodolsky, Denis/0000-0002-5401-792X; Scahill, Lawrence/0000-0001-5073-1707 FU National Institute of Mental Health (NIMH) by Research Units on Pediatric Psychopharmacology (RUPP) [U10MH66764, U10MH66766, U10MH66768]; Yale Clinical and Translational Science Award (CTSA) [UL1 RR024139]; Indiana University CTSA [UL1 RR025761]; Ohio State University CTSA from the National Center for Research Resources (NCRR) [UL1 RR025755]; NIMH; Shire; Seaside; Bristol-Myers Squibb; Johnson and Johnson; Eli Lilly and Co.; Autism Speaks; Neuropharm; Targacept; Janssen; Pediamed FX This work was funded by the National Institute of Mental Health (NIMH) by the following Research Units on Pediatric Psychopharmacology (RUPP) grants: U10MH66764 (Yale); U10MH66766 (Indiana University); U10MH66768 (Ohio State University). NIMH staff participated in the design and implementation, analysis of data, and authorship of the manuscript. Johnson and Johnson Pharmaceutical Research and Development provided active risperidone for the study, but had no role in the design and implementation, analysis of the data, or authorship of the manuscript. This publication was also supported by the Yale Clinical and Translational Science Award (CTSA) UL1 RR024139, Indiana University CTSA UL1 RR025761, and Ohio State University CTSA UL1 RR025755 from the National Center for Research Resources (NCRR). Drs. Scahill, McDougle, Amon, Johnson, Handen, Bearss, Dziura, Butter, Swiezy, Arnold, Stigler, Sukhodolsky, Lecavalier, Mulick, Pozdol, Nikolov, Korzekwa, and Vitiello, and Ms. Ritz, Ms. Holloway, Ms. Gavaletz, Ms. Kohn, Ms, Koenig, Ms. Grinnon, and Ms. Yu received salary support from NIMH in support of the study.; Dr. Scahill serves as a consultant for BioMarin, BoehringerIngelheim, Hoffman, NeuroSearch, and Pfizer. He has received research support from Shire and Seaside. Dr. Aman has sewed as a consultant to Bristol-Myers Squibb, BioMarin, Forest, Hoffman, Pfizer, and Supernus. He has received research support from Bristol-Myers Squibb and Johnson and Johnson. Dr. Arnold has served as a consultant to Abbott, BioMarin, Novartis, Naves, Organon, Shire, and Targacept. He has received research support from Eli Lilly and Co., Autism Speaks, Neuropharm, the National Institute of Mental Health (NIMH), Shire, and Targacept. Dr. McDougle has served as a consultant to Bristol-Myers Squibb and Forest. He has received research support from and served on the speakers' bureau for Bristol-Myers Squibb. Dr. Stigler has received research support from Bristol-Myers Squibb, Eli Lilly and Co., and Janssen. Dr. Handen has received research support from Bristol-Myers Squibb, Neuropharm, and Pediamed. He has served as a consultant to Forest and Eisai. Drs. Beams, Sukhodolsky, Nikolov, Dziura, Butter, Lecavalier, Mulick, Swiezy, Johnson, and Vitiello, and Ms. Koenig, Ms. Gavaletz, Ms. Yu, Ms. Holloway, Ms. Kohn, Ms. Pozdol, Ms. Korzekwa, and Ms. Grinnon report no biomedical financial interests or potential conflicts of interest. NR 32 TC 25 Z9 26 U1 2 U2 14 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 136 EP 146 DI 10.1016/j.jaac.2011.11.010 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 882YD UT WOS:000299598900005 PM 22265360 ER PT J AU Le Couteur, DG McLachlan, AJ de Cabo, R AF Le Couteur, David G. McLachlan, Andrew J. de Cabo, Rafael TI Aging, Drugs, and Drug Metabolism SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID CLINICAL-PHARMACOLOGY; LIFE-SPAN; LIVER; MICE C1 [Le Couteur, David G.; McLachlan, Andrew J.] Univ Sydney, Ctr Educ & Res Ageing, Concord Hosp, Concord, NSW 2139, Australia. [Le Couteur, David G.] Univ Sydney, ANZAC Res Inst, Concord Hosp, Concord, NSW 2139, Australia. [McLachlan, Andrew J.] Univ Sydney, Fac Pharm, Concord, NSW 2139, Australia. [de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Le Couteur, DG (reprint author), Univ Sydney, Ctr Educ & Res Ageing, Concord RG Hosp, Hosp Rd, Concord, NSW 2139, Australia. EM david.lecouteur@sydney.edu.au RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693; McLachlan, Andrew/0000-0003-4674-0242 NR 16 TC 4 Z9 4 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD FEB PY 2012 VL 67 IS 2 BP 137 EP 139 DI 10.1093/gerona/glr084 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 885RT UT WOS:000299799200004 PM 21768500 ER PT J AU Le Couteur, DG McLachlan, AJ Quinn, RJ Simpson, SJ de Cabo, R AF Le Couteur, David G. McLachlan, Andrew J. Quinn, Ronald J. Simpson, Stephen J. de Cabo, Rafael TI Aging Biology and Novel Targets for Drug Discovery SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID GENETICALLY HETEROGENEOUS MICE; CALORIE RESTRICTION MIMETICS; SMALL-MOLECULE ACTIVATORS; EXTENDING LIFE-SPAN; GROWTH-HORMONE; OXIDATIVE STRESS; SACCHAROMYCES-CEREVISIAE; CLINICAL-PHARMACOLOGY; DIETARY RESTRICTION; RETARDED GROWTH AB Despite remarkable technological advances in genetics and drug screening, the discovery of new pharmacotherapies has slowed and new approaches to drug development are needed. Research into the biology of aging is generating many novel targets for drug development that may delay all age-related diseases and be used long term by the entire population. Drugs that successfully delay the aging process will clearly become "blockbusters." To date, the most promising leads have come from studies of the cellular pathways mediating the longevity effects of caloric restriction (CR), particularly target of rapamycin and the sirtuins. Similar research into pathways governing other hormetic responses that influence aging is likely to yield even more targets. As aging becomes a more attractive target for drug development, there will be increasing demand to develop biomarkers of aging as surrogate outcomes for the testing of the effects of new agents on the aging process. C1 [Le Couteur, David G.; McLachlan, Andrew J.] Univ Sydney, Ctr Educ & Res Ageing, Concord Hosp, Sydney, NSW 2006, Australia. [Le Couteur, David G.] Univ Sydney, ANZAC Res Inst, Concord Hosp, Sydney, NSW 2006, Australia. [McLachlan, Andrew J.] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia. [Quinn, Ronald J.] Griffith Univ, Eskitis Inst, Brisbane, Qld 4111, Australia. [Simpson, Stephen J.] Univ Sydney, Sch Biol Sci, Sydney, NSW 2006, Australia. [de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Le Couteur, DG (reprint author), Concord RG Hosp, Ctr Educ & Res Ageing, Hosp Rd, Concord, NSW 2139, Australia. EM dlecouteur@med.usyd.edu.au RI Quinn, Ronald/A-7931-2008; de Cabo, Rafael/J-5230-2016; OI Quinn, Ronald/0000-0002-4022-2623; de Cabo, Rafael/0000-0002-3354-2442; Simpson, Stephen J./0000-0003-0256-7687; , rafael/0000-0003-2830-5693; McLachlan, Andrew/0000-0003-4674-0242 FU Australian National Health and Medical Research Council [570937, 571328]; Medical Foundation of the University of Sydney; Ageing and Alzheimer's Research Foundation FX This study was funded by the Australian National Health and Medical Research Council (grant 570937, 571328), the Medical Foundation of the University of Sydney, and the Ageing and Alzheimer's Research Foundation. NR 96 TC 24 Z9 24 U1 0 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD FEB PY 2012 VL 67 IS 2 BP 168 EP 174 DI 10.1093/gerona/glr095 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 885RT UT WOS:000299799200008 PM 21693687 ER PT J AU Katzman, W Cawthon, P Hicks, GE Vittinghoff, E Shepherd, J Cauley, JA Harris, T Simonsick, EM Strotmeyer, E Womack, C Kado, DM AF Katzman, Wendy Cawthon, Peggy Hicks, Gregory E. Vittinghoff, Eric Shepherd, John Cauley, Jane A. Harris, Tamara Simonsick, Eleanor M. Strotmeyer, Elsa Womack, Catherine Kado, Deborah M. TI Association of Spinal Muscle Composition and Prevalence of Hyperkyphosis in Healthy Community-Dwelling Older Men and Women SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Kyphosis; Hyperkyphosis; Prevalence; Spinal muscle; Fat infiltration ID FLEXION-RELAXATION PHENOMENON; LOWER-EXTREMITY PERFORMANCE; BODY-COMPOSITION; RANCHO-BERNARDO; OSTEOPOROTIC FRACTURES; VERTEBRAL FRACTURES; PHYSICAL FUNCTION; FLEXED POSTURE; BACK-PAIN; SKELETAL-MUSCLE AB Background. Older adults with hyperkyphosis are at increased risk of falls, fractures, and functional decline. Modifiable risk factors for hyperkyphosis have not been well studied. Our objective was to determine whether spinal muscle area and density are associated with hyperkyphosis, independent of age, race, sex, bone mineral density, and trunk fat. Methods. Using data from the Pittsburgh site of the Health, Aging, and Body Composition study, we performed a baseline cross-sectional analysis. Participants were black and white men and women 70-79 years old (N = 1172), independent in activities of daily living and able to walk 1/4 mile and up 10 steps without resting. We measured Cobb's angle of kyphosis from supine lateral scout computed tomography scans, and categorized hyperkyphosis as Cobb's angle >40 degrees. Axial images from lateral scout computed tomography scans assessed spinal extensor muscle cross-sectional area and density (proxy for fat infiltration). Results. In our sample, 21% had hyperkyphosis. Prevalence in black men was 11%; in white men, 17%; in black women, 26%; and in white women, 30%. In multivariate analysis, each standard deviation increase in muscle density was associated with a 29% reduction in the odds of hyperkyphosis, independent of covariates. Muscle area was not significantly associated with hyperkyphosis. Conclusions. Lower spinal muscle density is associated with hyperkyphosis in healthy community-dwelling older adults. This potentially modifiable risk factor could be targeted in exercise interventions. Randomized trials are needed to determine whether an exercise program targeting spinal muscle density reduces hyperkyphosis and in turn improves health outcomes. C1 [Katzman, Wendy] Univ Calif San Francisco, Dept Phys Therapy & Rehabil Sci, San Francisco, CA 94143 USA. [Cawthon, Peggy] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Hicks, Gregory E.] Univ Delaware, Dept Phys Therapy, Newark, DE 19716 USA. [Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shepherd, John] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Cauley, Jane A.; Strotmeyer, Elsa] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Simonsick, Eleanor M.] NIA, Dept Epidemiol, Clin Res Branch, Baltimore, MD 21224 USA. [Womack, Catherine] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Kado, Deborah M.] Univ Calif Los Angeles, Dept Orthopaed Surg, Los Angeles, CA 90024 USA. [Kado, Deborah M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Katzman, W (reprint author), Univ Calif San Francisco, Dept Phys Therapy & Rehabil Sci, 1500 Owens,Suite 400, San Francisco, CA 94143 USA. EM wendy.katzman@ucsfmedctr.org RI Strotmeyer, Elsa/F-3015-2014; OI Strotmeyer, Elsa/0000-0002-4093-6036; Cauley, Jane A/0000-0003-0752-4408 FU UCSF; National Institute of Child Health and Human Development; Office of Research on Women's Health [5 K12 HD052163]; National Institutes of Health (NIH) [2R56AG024246]; National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR [R01-NR012459]; NIH, NIA FX This research was supported in part by the UCSF-Kaiser Building Interdisciplinary Research Careers in Women's Health and cofunded by the National Institute of Child Health and Human Development and the Office of Research on Women's Health 5 K12 HD052163; National Institutes of Health (NIH) Director's Bridge Award 2R56AG024246; National Institute on Aging (NIA) Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106, NIA grant R01-AG028050, and NINR grant R01-NR012459; Intramural Research Program of the NIH, NIA, and the UCSF Mount Zion Health Fund. NR 38 TC 21 Z9 22 U1 2 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD FEB PY 2012 VL 67 IS 2 BP 191 EP 195 DI 10.1093/gerona/glr160 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 885RT UT WOS:000299799200011 PM 21878482 ER PT J AU Pei, Y Lan, Z Wang, KR Garcia-Gonzalez, M He, N Dicks, E Parfrey, P Germino, G Watnick, T AF Pei, York Lan, Zheng Wang, Kairong Garcia-Gonzalez, Miguel He, Ning Dicks, Elizabeth Parfrey, Patrick Germino, Gregory Watnick, Terry TI A missense mutation in PKD1 attenuates the severity of renal disease SO KIDNEY INTERNATIONAL LA English DT Article DE ADPKD; functional assay; hypomorphic allele; missense variant; mutation analysis ID POLYCYSTIC KIDNEY-DISEASE; MOLECULAR DIAGNOSTICS; GENE; EXPRESSION; ALLELES; PATHOGENESIS; ADPKD AB Mutations of PKD1 and PKD2 account for most cases of autosomal dominant polycystic kidney disease (ADPKD). Compared with PKD2, patients with PKD1 typically have more severe renal disease. Here, we report a follow-up study of a unique multigeneration family with bilineal ADPKD (NFL10) in which a PKD1 disease haplotype and a PKD2 (L736X) mutation co-segregated with 18 and 14 affected individuals, respectively. In our updated genotype-phenotype analysis of the family, we found that PKD1-affected individuals had uniformly mild renal disease similar to the PKD2-affected individuals. By sequencing all the exons and splice junctions of PKD1, we identified two missense mutations (Y528C and R1942H) from a PKD1-affected individual. Although both variants were predicted to be damaging to the mutant protein, only Y528C co-segregated with all of the PKD1-affected individuals in NFL10. Studies in MDCK cells stably expressing wild-type and mutant forms of PKD found that cell lines expressing the Y528C variant formed cysts in culture and displayed increased rates of growth and apoptosis. Thus, Y528C functions as a hypomorphic PKD1 allele. These findings have important implications for pathogenic mechanisms and molecular diagnostics of ADPKD. Kidney International (2012) 81, 412-417; doi:10.1038/ki.2011.370; published online 26 October 2011 C1 [Pei, York; Wang, Kairong; He, Ning] Univ Toronto, Div Nephrol, Toronto, ON, Canada. [Lan, Zheng; Garcia-Gonzalez, Miguel; Germino, Gregory; Watnick, Terry] Johns Hopkins Sch Med, Div Nephrol, Baltimore, MD 21205 USA. [Garcia-Gonzalez, Miguel] Complexo Hosp Univ Santiago, Lab Invest Nefrol, Santiago De Compostela, Spain. [Dicks, Elizabeth; Parfrey, Patrick] Mem Univ Newfoundland, Div Nephrol, St John, NF, Canada. [Germino, Gregory] NIDDK, NIH, Bethesda, MD USA. RP Pei, Y (reprint author), Univ Hlth Network, Div Nephrol, 8N838,585 Univ Ave, Toronto, ON M5G 2N2, Canada. EM york.pei@uhn.on.ca; twatnick@jhmi.edu RI Garcia-Gonzalez, Miguel/G-6920-2011; OI Germino, Gregory/0000-0002-3609-5588 FU Canadian Institutes of Health Research (CIHR) [MOP77806]; National Institutes of Health [RO1DK0617, RO1GM73704]; NIDDK [P30 DK090868]; [DK48006] FX We are indebted to all the participating members of the NFL10 family. This work was supported by grants from the Canadian Institutes of Health Research (CIHR; MOP77806) to YP, from the National Institutes of Health (RO1DK0617 and RO1GM73704) to TW and (DK48006 and NIDDK Intramural Research Program) to GG, and by the CIHR Distinguished Scientist Award to PP. These studies utilized Resources provided by the NIDDK-sponsored Johns Hopkins PKD Research and Clinical Core Center (P30 DK090868). NR 28 TC 23 Z9 23 U1 0 U2 1 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 412 EP 417 DI 10.1038/ki.2011.370 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 886JJ UT WOS:000299850400012 PM 22031115 ER PT J AU Masood, MA Rao, RP Acharya, JK Blonder, J Veenstra, TD AF Masood, M. Athar Rao, Raghavendra P. Acharya, Jairaj K. Blonder, Josip Veenstra, Timothy D. TI Quantitation of Multiple Sphingolipid Classes Using Normal and Reversed-Phase LC-ESI-MS/MS: Comparative Profiling of Two Cell Lines SO LIPIDS LA English DT Article DE Ceramides; Hexosylceramides; Sphingomyelins; Normal-phase and reversed-phase LC-MS/MS; Quantitation; Mouse embryonic fibroblast; Human embryonic kidney cells ID TANDEM MASS-SPECTROMETRY; CORONARY-HEART-DISEASE; FATTY-ACIDS; SPHINGOSINE 1-PHOSPHATE; BIOLOGICAL SAMPLES; LIFE-SPAN; LIPIDOMICS; CANCER; RISK; DEGENERATION AB Sphingolipids are an important class of compounds that regulate signal transduction and other vital cellular processes. Herein, we report sensitive normal and reversed phase LC-MS/MS methods for quantitation of multiple sphingolipid classes. In the normal-phase ESI/MS/MS method, a high content of organic solvents was utilized, which, although it included hexane, ethyl acetate, acetonitrile containing 2% methanol, 1-2% acetic acid, and 5 mM ammonium acetate, resulted in a very efficient electrospray ionization of the ceramides (Cers) and hexosylceramides (MHCers). Three normal-phase LC-MS/MS methods using segmented phases were developed to specifically target Cers, MHCers, or sphingomyelins (SMs). This segmentation scheme increases the number of data points acquired for a given analyte and enhances the sensitivity and specificity of the measurements. Nine separate reversed phase chromatography methods were developed for the three classes of compounds. These assays were used for comparing the levels of Cers, SMs, and MHCers from mouse embryonic fibroblast (pMEF) and human embryonic kidney (HEK293) cells. These findings were then compared with the reported data from RAW264.7 mouse macrophage cells, BHK21 hamster cells, and human plasma and serum samples. The analysis of cell lines, using both normal and reversed phase chromatography, revealed discrimination based on the type of chromatography chosen, while sphingolipid assays of samples containing different amounts of protein showed different results, even after normalizing for protein content. Also, LC/MS/MS profiles were provided for the classes and individual compounds so that they could be used as "molecular profiles" for class or individual sample analysis. C1 [Masood, M. Athar; Blonder, Josip; Veenstra, Timothy D.] SAIC Frederick Inc, Lab Prote & Analyt Technol, NCI, Frederick, MD 21702 USA. [Rao, Raghavendra P.; Acharya, Jairaj K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. RP Masood, MA (reprint author), SAIC Frederick Inc, Lab Prote & Analyt Technol, NCI, Frederick, MD 21702 USA. EM masoodaa@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 48 TC 5 Z9 5 U1 0 U2 41 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 J9 LIPIDS JI Lipids PD FEB PY 2012 VL 47 IS 2 BP 209 EP 226 DI 10.1007/s11745-011-3633-2 PG 18 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 882AI UT WOS:000299533100010 PM 22124806 ER PT J AU Bandettini, PA Bowtell, R Jezzard, P Turner, R AF Bandettini, Peter A. Bowtell, Richard Jezzard, Peter Turner, Robert TI Ultrahigh field systems and applications at 7 T and beyond: Progress, pitfalls, and potential SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE high field; fMRI; MRI; DTI; susceptibility ID BRAIN-TISSUE; MRI; ORIENTATION; SUSCEPTIBILITY; SENSITIVITY; FREQUENCY; MULTIPLE; IMAGE; MAP AB About 150 researchers around the world convened at the Chateau Lake Louise on February 2023, 2011 to present and discuss the latest research in human and animal imaging and spectroscopy at field strengths of 7 T or above (termed ultrahigh field) at the third ISMRM-sponsored high field workshop. The clear overall message from the workshop presentations and discussion is that ultrahigh field imaging is gaining momentum with regard to new clinically relevant findings, anatomic and functional MRI results, susceptibility contrast advancements, solutions to high field-related image quality challenges, and to generally push the limits of resolution and speed of high field imaging. This meeting report is organized in a manner reflecting the meeting organization itself, covering the seven sessions that were approximately titled: (1) high field overview from head to body to spectroscopy; (2) susceptibility imaging; (3) proffered session on susceptibility, ultrafast imaging, unique contrast at 7 T, and angiography; (4) neuroscience applications; (5) proffered session on coils, shimming, parallel imaging, diffusion tensor imaging, and MRI-PET fusion; (6) high field animal imaging and spectroscopy, as well as a vendor overview, and (7) Cutting edge technology at 7 T. Magn Reson Med, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Bethesda, MD 20882 USA. [Bandettini, Peter A.] NIMH, Funct MRI Core Facil, Bethesda, MD 20882 USA. [Bowtell, Richard] Univ Nottingham, Sir Peter Mansfield Magnet Resonance Ctr, Nottingham NG7 2RD, England. [Jezzard, Peter] Univ Oxford, Nuffield Dept Clin Neurosci, FMRIB Ctr, Oxford, England. [Turner, Robert] Max Planck Inst Human Cognit & Brain Sci, Leipzig, Germany. RP Bandettini, PA (reprint author), NIMH, Sect Funct Imaging Methods, Bldg 10,Room 1D80,10 Ctr Dr,MSC 1148, Bethesda, MD 20882 USA. EM Bandettini@nih.gov OI Bowtell, Richard/0000-0001-8656-412X; Turner, Robert/0000-0001-5055-9644; Jezzard, Peter/0000-0001-7912-2251 FU Intramural NIH HHS [ZIA MH002783-09, Z99 MH999999]; Medical Research Council [G0700399, G0901321] NR 27 TC 16 Z9 16 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD FEB PY 2012 VL 67 IS 2 BP 317 EP 321 DI 10.1002/mrm.23151 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 880AM UT WOS:000299376500005 PM 22083719 ER PT J AU Grewal, J Carmichael, SL Yang, W Shaw, GM AF Grewal, Jagteshwar Carmichael, Suzan L. Yang, Wei Shaw, Gary M. TI Paternal Age and Congenital Malformations in Offspring in California, 1989-2002 SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Congenital malformations; Paternal age; Birth defects ID BIRTH-DEFECTS; DELAYED CHILDBEARING; MATERNAL AGE; RISK; ASSOCIATION; POPULATION; PREGNANCY; NORWAY; OLDER AB This study examined the association between paternal age and a wide range of structural birth defects. Data were drawn from The California Birth Defects Monitoring Program, a population-based active surveillance system for collecting information on infants and fetuses with defects born between 1989 and 2002. The analysis included 46,114 cases with defects, plus a random sample of 36,838 non-malformed births. After adjustment for maternal age, risks of anomalies of the nervous system for 38 and 42 year-old fathers, as compared to 29 year-old fathers, were 1.05-fold [1.00, 1.11] and 1.10-fold [1.02, 1.18] higher, respectively. Similar results were observed for anomalies of the limbs, where 38 and 42 year-old fathers had a 1.06-fold [1.02, 1.11] and 1.11-fold [1.05, 1.18] higher risk, respectively. Risks of anomalies of the integument were 1.05-fold [1.00, 1.09] and 1.10-fold [1.03, 1.16] higher for 38 and 42 year olds, respectively. Young paternal age, i.e., less than 29 years, was associated with an increased risk of amniotic bands (OR: 0.87 [0.78, 0.97]), pyloric stenosis (OR: 0.93 [0.90, 0.96]) and anomalies of the great veins (OR: 0.93 [0.87, 1.00]). In sum, both advanced and young paternal age was associated with select birth defects in California between 1989 and 2002. C1 [Carmichael, Suzan L.; Yang, Wei; Shaw, Gary M.] Stanford Univ, Palo Alto, CA 94304 USA. [Grewal, Jagteshwar] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. RP Carmichael, SL (reprint author), Stanford Univ, Palo Alto, CA 94304 USA. EM scarmichael@stanford.edu OI Grewal, Jagteshwar/0000-0002-0141-4876 NR 29 TC 7 Z9 7 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 EI 1573-6628 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD FEB PY 2012 VL 16 IS 2 BP 385 EP 392 DI 10.1007/s10995-011-0759-z PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 879YJ UT WOS:000299370400013 PM 21344170 ER PT J AU Abrames, E Folio, L AF Abrames, Erik Folio, Les TI CT Severity Spectrum of Penetrating Eye Injuries From Blasts SO MILITARY MEDICINE LA English DT Article ID IRAQI FREEDOM; ORBIT AB Penetrating eye trauma from blasts can result in a vast spectrum of ocular injuries. Several cases of orbital trauma are reviewed, all of which occurred during combat operations and treated M an Air Force Theater Hospital. Computed tomography was used as the primary imaging modality and proved crucial in determining the extent of ocular injury. This report focuses on factors we believe affect globe salvageability, reviews imaging modalities in theater, and briefly discusses management in theater and aeromedical evacuation after initial injury. C1 [Abrames, Erik] Yokota Air Base Hosp, Med Grp 374th, Yokota Air Base, Japan. [Folio, Les] NIH, Bethesda, MD 20892 USA. RP Abrames, E (reprint author), Yokota Air Base Hosp, Med Grp 374th, Bldg 4412,McGuire Ave, Yokota Air Base, Japan. NR 10 TC 1 Z9 1 U1 0 U2 2 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD FEB PY 2012 VL 177 IS 2 BP 169 EP 173 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 886KC UT WOS:000299852300010 PM 22360062 ER PT J AU Jeong, JH Kim, HJ Kim, KH Shin, M Hong, Y Rhee, JH Schneider, TD Choy, HE AF Jeong, Jae-Ho Kim, Hyun-Ju Kim, Kun-Hee Shin, Minsang Hong, Yeongjin Rhee, Joon Haeng Schneider, Thomas D. Choy, Hyon E. TI An unusual feature associated with LEE1 P1 promoters in enteropathogenic Escherichia coli (EPEC) SO MOLECULAR MICROBIOLOGY LA English DT Article ID ENTEROCYTE EFFACEMENT GENES; START SITE SELECTION; RNA-POLYMERASE; REITERATIVE TRANSCRIPTION; H-NS; REGULATORY REGION; GALP2 PROMOTER; SEQUENCE LOGOS; LOCUS; DNA AB Transcription start points in bacteria are influenced by the nature of the RNA polymerase.promoter interaction. For Escherichia coli RNA polymerase holoenzyme containing sigma 70, it is presumed that specific sequence in one or more of the -10, extended -10 and -35 elements of the promoter guides the RNAP to select the cognate start point. Here, we investigated the promoter driving expression of the LEE1 operon in enteropathogenic E. coli and found two promoters separated by 10 bp, LEE1 P1A (+1) and LEE1 P1B (+10) using various in vitro biochemical tools. A unique feature of P1B was the presence of multiple transcription starts from five neighbouring As at the initial transcribed region. The multiple products did not arise from stuttering synthesis. Analytical software based on information theory was employed to determine promoter elements. The concentration of the NTP pool altered the preferred transcription start points, albeit the underlying mechanism is elusive. Under in vivo conditions, dominant P1B, but not P1A, was subject to regulation by IHF. C1 [Jeong, Jae-Ho; Kim, Hyun-Ju; Kim, Kun-Hee; Shin, Minsang; Hong, Yeongjin; Choy, Hyon E.] Chonnam Natl Univ, Sch Med, Ctr Host Def Enteropathogen Bacteria Infect, Kwangju 501746, South Korea. [Jeong, Jae-Ho; Kim, Hyun-Ju; Kim, Kun-Hee; Shin, Minsang; Hong, Yeongjin; Rhee, Joon Haeng; Choy, Hyon E.] Chonnam Natl Univ, Sch Med, Dept Microbiol, Kwangju 501746, South Korea. [Schneider, Thomas D.] NCI, NIH, Gene Regulat & Chromosome Biol Lab, Nci Frederick, MD USA. RP Choy, HE (reprint author), Chonnam Natl Univ, Sch Med, Ctr Host Def Enteropathogen Bacteria Infect, Kwangju 501746, South Korea. EM hyonchoy@jnu.ac.kr OI Schneider, Thomas/0000-0002-9841-1531 FU Korea Science and Engineering Foundation; MOST [2007-04213]; Ministry of Knowledge Economy (MKE) [RTI05-01-01]; NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by the Korea Science and Engineering Foundation grant that was funded by MOST (No. 2007-04213). J.H.R. was supported by Grant No. RTI05-01-01 from the Regional Technology Innovation Program of the Ministry of Knowledge Economy (MKE). T.S. was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 53 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 2012 VL 83 IS 3 BP 612 EP 622 DI 10.1111/j.1365-2958.2011.07956.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 878JE UT WOS:000299251900012 PM 22229878 ER PT J AU Crockett, MJ Clark, L Roiser, JP Robinson, OJ Cools, R Chase, HW den Ouden, H Apergis-Schoute, A Campbell-Meikeljohn, D Seymour, B Sahakian, BJ Rogers, RD Robbins, TW AF Crockett, M. J. Clark, L. Roiser, J. P. Robinson, O. J. Cools, R. Chase, H. W. den Ouden, H. Apergis-Schoute, A. Campbell-Meikeljohn, D. Seymour, B. Sahakian, B. J. Rogers, R. D. Robbins, T. W. TI Converging evidence for central 5-HT effects in acute tryptophan depletion SO MOLECULAR PSYCHIATRY LA English DT Letter ID SEROTONIN; RELEASE; MEMORY; RATS C1 [Crockett, M. J.; Apergis-Schoute, A.; Sahakian, B. J.; Robbins, T. W.] Behav & Clin Neurosci Inst, Cambridge, England. [Crockett, M. J.; Clark, L.; Apergis-Schoute, A.; Robbins, T. W.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. [Roiser, J. P.] UCL, Inst Cognit Neurosci, London, England. [Robinson, O. J.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Cools, R.; den Ouden, H.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, NL-6525 ED Nijmegen, Netherlands. [Cools, R.; den Ouden, H.] Dept Psychiat, Nijmegen, Netherlands. [Chase, H. W.] Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Campbell-Meikeljohn, D.] Aarhus Univ, CFIN, Aarhus, Denmark. [Seymour, B.] UCL, Wellome Trust Ctr Neuroimaging, London, England. [Sahakian, B. J.] Univ Cambridge, Dept Psychiat, Cambridge, England. [Rogers, R. D.] Univ Oxford, Dept Psychiat, Oxford, England. [Rogers, R. D.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. RP Crockett, MJ (reprint author), Behav & Clin Neurosci Inst, Cambridge, England. EM mollycrockett@gmail.com RI Roiser, Jonathan/A-1791-2010; den Ouden, Hanneke/D-3019-2009; Robinson, Oliver/B-3646-2011; Cools, Roshan/D-1905-2010; Crockett, Molly/F-8217-2014; OI den Ouden, Hanneke/0000-0001-7039-5130; Robinson, Oliver/0000-0002-3100-1132; Crockett, Molly/0000-0001-8800-410X; Seymour, Ben/0000-0003-1724-5832; Campbell-Meiklejohn, Daniel/0000-0002-8916-265X NR 12 TC 26 Z9 26 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD FEB PY 2012 VL 17 IS 2 BP 121 EP 123 DI 10.1038/mp.2011.106 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 885SZ UT WOS:000299802400004 PM 21876544 ER PT J AU Stark, MS Woods, SL Gartside, MG Bonazzi, VF Dutton-Regester, K Aoude, LG Chow, D Sereduk, C Niemi, NM Tang, NY Ellis, JJ Reid, J Zismann, V Tyagi, S Muzny, D Newsham, I Wu, YQ Palmer, JM Pollak, T Youngkin, D Brooks, BR Lanagan, C Schmidt, CW Kobe, B MacKeigan, JP Yin, HW Brown, KM Gibbs, R Trent, J Hayward, NK AF Stark, Mitchell S. Woods, Susan L. Gartside, Michael G. Bonazzi, Vanessa F. Dutton-Regester, Ken Aoude, Lauren G. Chow, Donald Sereduk, Chris Niemi, Natalie M. Tang, Nanyun Ellis, Jonathan J. Reid, Jeffrey Zismann, Victoria Tyagi, Sonika Muzny, Donna Newsham, Irene Wu, YuanQing Palmer, Jane M. Pollak, Thomas Youngkin, David Brooks, Bradford R. Lanagan, Catherine Schmidt, Christopher W. Kobe, Bostjan MacKeigan, Jeffrey P. Yin, Hongwei Brown, Kevin M. Gibbs, Richard Trent, Jeffrey Hayward, Nicholas K. TI Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing SO NATURE GENETICS LA English DT Article ID MALIGNANT-MELANOMA; HUMAN CANCER; APOPTOSIS; KINASE-1; TEMOZOLOMIDE; INHIBITION; ACTIVATION; GENES; BRAF AB We sequenced eight melanoma exomes to identify new somatic mutations in metastatic melanoma. Focusing on the mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) family, we found that 24% of melanoma cell lines have mutations in the protein-coding regions of either MAP3K5 or MAP3K9. Structural modeling predicted that mutations in the kinase domain may affect the activity and regulation of these protein kinases. The position of the mutations and the loss of heterozygosity of MAP3K5 and MAP3K9 in 85% and 67% of melanoma samples, respectively, together suggest that the mutations are likely to be inactivating. In in vitro kinase assays, MAP3K5 1780F and MAP3K9 W333* variants had reduced kinase activity. Overexpression of MAP3K5 or MAP3K9 mutants in HEK293T cells reduced the phosphorylation of downstream MAP kinases. Attenuation of MAP3K9 function in melanoma cells using siRNA led to increased cell viability after temozolomide treatment, suggesting that decreased MAP3K pathway activity can lead to chemoresistance in melanoma. C1 [Stark, Mitchell S.; Woods, Susan L.; Gartside, Michael G.; Bonazzi, Vanessa F.; Dutton-Regester, Ken; Aoude, Lauren G.; Tyagi, Sonika; Palmer, Jane M.; Pollak, Thomas; Lanagan, Catherine; Schmidt, Christopher W.; Hayward, Nicholas K.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Dutton-Regester, Ken] Queensland Univ Technol, Brisbane, Qld 4001, Australia. [Aoude, Lauren G.] Univ Queensland, Sch Med, Brisbane, Qld, Australia. [Chow, Donald; Sereduk, Chris; Ellis, Jonathan J.; Zismann, Victoria; Youngkin, David; Yin, Hongwei; Brown, Kevin M.; Trent, Jeffrey] Translat Genom Res Inst, Phoenix, AZ USA. [Niemi, Natalie M.; Brooks, Bradford R.; MacKeigan, Jeffrey P.; Trent, Jeffrey] Van Andel Res Inst, Grand Rapids, MI USA. [Ellis, Jonathan J.; Kobe, Bostjan] Univ Queensland, Sch Chem & Mol Biosci, Inst Mol Biosci, Brisbane, Qld, Australia. [Ellis, Jonathan J.; Kobe, Bostjan] Univ Queensland, Ctr Infect Dis Res, Brisbane, Qld, Australia. [Reid, Jeffrey; Muzny, Donna; Newsham, Irene; Wu, YuanQing; Gibbs, Richard] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Brown, Kevin M.] NCI, Adv Technol Ctr, Gaithersburg, MD USA. RP Hayward, NK (reprint author), Queensland Inst Med Res, Brisbane, Qld 4006, Australia. EM nick.hayward@qimr.edu.au RI Kobe, Bostjan/D-1292-2009; Ellis, Jonathan/F-2920-2010; Stark, Mitchell/E-3542-2010; Aoude, Lauren/C-7484-2014; hayward, nicholas/C-1367-2015; OI Kobe, Bostjan/0000-0001-9413-9166; Ellis, Jonathan/0000-0003-0410-5064; Stark, Mitchell/0000-0002-4510-2161; Aoude, Lauren/0000-0003-1448-3923; hayward, nicholas/0000-0003-4760-1033; Woods, Susan/0000-0002-8955-2017; Bonazzi, Vanessa/0000-0002-2574-0334 FU National Health and Medical Research Council of Australia; Australian Centre for Vaccine Development; US National Cancer Institute [5U01CA129447]; US National Cancer Institute, Division of Cancer Epidemiology and Genetics FX The authors would like to acknowledge M. Aziz for data processing, M. Kassner for technical support and J.-C. Deza for graphics support. This work was funded through grants from the National Health and Medical Research Council of Australia, the Australian Centre for Vaccine Development, the US National Cancer Institute (5U01CA129447 to J.T.), the US National Cancer Institute, Division of Cancer Epidemiology and Genetics (to K.M.B.), and a charitable donation by Francis Najafi (to K.M.B. and IT.). NR 24 TC 95 Z9 96 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2012 VL 44 IS 2 BP 165 EP 169 DI 10.1038/ng.1041 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 883WA UT WOS:000299664400013 PM 22197930 ER PT J AU O'Seaghdha, CM Fox, CS AF O'Seaghdha, Conall M. Fox, Caroline S. TI Genome-wide association studies of chronic kidney disease: what have we learned? SO NATURE REVIEWS NEPHROLOGY LA English DT Review ID STAGE RENAL-DISEASE; MANGANESE SUPEROXIDE-DISMUTASE; TYPE-2 DIABETIC-PATIENTS; CARNOSINASE GENE CNDP1; AFRICAN-AMERICANS; IGA NEPHROPATHY; PROSPECTIVE COHORT; NATURAL-SELECTION; JAPANESE PATIENTS; SERUM CREATININE AB The past 3 years have witnessed a dramatic expansion in our knowledge of the genetic determinants of estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). However, heritability estimates of eGFR indicate that we have only identified a small proportion of the total heritable contribution to the phenotypic variation. The majority of associations reported from genome-wide association studies identify genomic regions of interest and further work will be required to identify the causal variants responsible for a specific phenotype. Progress in this area is likely to stem from the identification of novel risk genotypes, which will offer insight into the pathogenesis of disease and potential novel therapeutic targets. Follow-up studies stimulated by findings from genome-wide association studies of kidney disease are already yielding promising results, such as the identification of an association between urinary uromodulin levels and incident CKD. Although this work is at an early stage, prospects for progress in our understanding of CKD and its treatment look more promising now than at any point in the past. C1 [O'Seaghdha, Conall M.; Fox, Caroline S.] Natl Heart Lung & Blood Inst, Framingham Heart Study & Ctr Populat Studies, Framingham, MA 01702 USA. RP Fox, CS (reprint author), Natl Heart Lung & Blood Inst, Framingham Heart Study & Ctr Populat Studies, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 107 TC 23 Z9 23 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD FEB PY 2012 VL 8 IS 2 BP 89 EP 99 DI 10.1038/nrneph.2011.189 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 888AK UT WOS:000299976000008 PM 22143329 ER PT J AU Geocadin, RG Bleck, TP Koroshetz, WJ Robertson, CS Zaidat, OO LeRoux, PD Wijman, CAC Suarez, JI AF Geocadin, R. G. Bleck, T. P. Koroshetz, W. J. Robertson, C. S. Zaidat, O. O. LeRoux, P. D. Wijman, C. A. C. Suarez, J. I. TI Research Priorities in Neurocritical Care SO NEUROCRITICAL CARE LA English DT Review DE Neurocritical care; Critical care; Clinical trials; Research network; Consortium ID TRAUMATIC BRAIN-INJURY; VENOUS THROMBOEMBOLISM; CRITICALLY-ILL; INTENSIVE-CARE; HEAD-INJURY; TRANSFUSION; PROPHYLAXIS; MORTALITY; RECOMMENDATIONS; MULTICENTER AB This summary of the last session of the First Neurocritical Care Research Conference reviews the discussions about research priorities in neurocritical care. The first presentation reviewed current projects funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health and potential models to follow including an independent Neurocritical Care Network or the creation of such a network with the goal of collaborating with already existing ones. Experienced neurointensivists then presented their views on the most common and important research questions that need to be answered and investigated in the field. Finally, utility of clinical registries was discussed emphasizing their importance as hypothesis generators. During the group discussion, interests in comparative effectiveness research, the use of physiological endpoints from monitoring and alternate trial design were expressed. C1 [Geocadin, R. G.] Johns Hopkins Univ, Dept Neurol, Sch Med, Johns Hopkins Hosp, Baltimore, MD 21287 USA. [Geocadin, R. G.] Johns Hopkins Univ, Dept Anesthesiol Crit Care Med, Sch Med, Johns Hopkins Hosp, Baltimore, MD 21287 USA. [Geocadin, R. G.] Johns Hopkins Univ, Dept Neurosurg, Sch Med, Johns Hopkins Hosp, Baltimore, MD 21287 USA. [Bleck, T. P.] Rush Univ, Dept Neurol Sci, Chicago, IL 60612 USA. [Bleck, T. P.] Rush Univ, Dept Neurosurg, Chicago, IL 60612 USA. [Bleck, T. P.] Rush Univ, Dept Med, Chicago, IL 60612 USA. [Bleck, T. P.] Rush Univ, Dept Anesthesiol, Chicago, IL 60612 USA. [Koroshetz, W. J.] NINDS, NIH, Bethesda, MD 20892 USA. [Robertson, C. S.] Baylor Coll Med, Dept Neurol Surg, Houston, TX 77030 USA. [Zaidat, O. O.] Med Coll Wisconsin, Dept Neurol & Neurosurg, Milwaukee, WI 53226 USA. [LeRoux, P. D.] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. [Wijman, C. A. C.] Stanford Univ, Dept Neurol, Palo Alto, CA 94304 USA. [Suarez, J. I.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Geocadin, RG (reprint author), Johns Hopkins Univ, Dept Neurol, Sch Med, Johns Hopkins Hosp, 600 N Wolfe St,Meyer 8-140, Baltimore, MD 21287 USA. EM rgeocad1@jhmi.edu OI 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 26 TC 1 Z9 1 U1 0 U2 4 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 35 EP 41 DI 10.1007/s12028-011-9611-y PG 7 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 881QW UT WOS:000299502500006 PM 21792752 ER PT J AU Liu, ZM de Zwart, JA van Gelderen, P Kuo, LW Duyn, JH AF Liu, Zhongming de Zwart, Jacco A. van Gelderen, Peter Kuo, Li-Wei Duyn, Jeff H. TI Statistical feature extraction for artifact removal from concurrent fMRI-EEG recordings SO NEUROIMAGE LA English DT Article DE Gradient artifact; Ballistocardiogram; Singular value decomposition; Independent component analysis; Mutual information ID INDEPENDENT COMPONENT ANALYSIS; BALLISTOCARDIOGRAM ARTIFACT; FUNCTIONAL MRI; SIMULTANEOUS EEG/FMRI; IMAGING-ARTIFACT; PULSE ARTIFACT; REDUCTION; SCANNER; ELECTROENCEPHALOGRAM; IDENTIFICATION AB We propose a set of algorithms for sequentially removing artifacts related to MRI gradient switching and cardiac pulsations from electroencephalography (EEG) data recorded during functional magnetic resonance imaging (fMRI). Special emphasis is directed upon the use of statistical metrics and methods for the extraction and selection of features that characterize gradient and pulse artifacts. To remove gradient artifacts, we use channel-wise filtering based on singular value decomposition (SVD). To remove pulse artifacts, we first decompose data into temporally independent components and then select a compact cluster of components that possess sustained high mutual information with the electrocardiogram (ECG). After the removal of these components, the time courses of remaining components are filtered by SVD to remove the temporal patterns phase-locked to the cardiac timing markers derived from the ECG. The filtered component time courses are then inversely transformed into multi-channel EEG time series free of pulse artifacts. Evaluation based on a large set of simultaneous EEG-fMRI data obtained during a variety of behavioral tasks, sensory stimulations and resting conditions showed excellent data quality and robust performance attainable with the proposed methods. These algorithms have been implemented as a Matlab-based toolbox made freely available for public access and research use. Published by Elsevier Inc. C1 [Liu, Zhongming; de Zwart, Jacco A.; van Gelderen, Peter; Kuo, Li-Wei; Duyn, Jeff H.] NINDS, Adv MRI Sect, LFMI, NIH, Bethesda, MD 20982 USA. RP Liu, ZM (reprint author), NINDS, Adv MRI Sect, LFMI, NIH, Bldg 10,Room B1D-723,9000 Rockville Pike,MSC 1065, Bethesda, MD 20982 USA. EM liuz5@mail.nih.gov RI Kuo, Li-Wei/G-4007-2011 FU National Institute of Neurological Disorders and Stroke, National Institutes of Health FX The authors appreciate Dr. Hanchuan Peng for kindly sharing his C program for computing entropy and mutual information, Dr. Masaki Fukunaga and Susan Guttman for their assistance in data collection and Drs. Qi Duan and Hendrik Mandelkow for useful discussions and carefully reading this manuscript. This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 46 TC 26 Z9 27 U1 3 U2 18 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 2073 EP 2087 DI 10.1016/j.neuroimage.2011.10.042 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 881NS UT WOS:000299494000011 PM 22036675 ER PT J AU Kimura, Y Simeon, FG Zoghbi, SS Zhang, Y Hatazawa, J Pike, VW Innis, RB Fujita, M AF Kimura, Yasuyuki Simeon, Fabrice G. Zoghbi, Sami S. Zhang, Yi Hatazawa, Jun Pike, Victor W. Innis, Robert B. Fujita, Masahiro TI Quantification of metabotropic glutamate subtype 5 receptors in the brain by an equilibrium method using F-18-SP203 SO NEUROIMAGE LA English DT Article DE F-18-SP203; Bolus plus constant infusion; Equilibrium method; Metabotropic glutamate subtype 5 receptor (mGluR5); Positron emission tomography (PET) ID POSITRON-EMISSION-TOMOGRAPHY; CONSTANT INFUSION; QUANTITATION; BOLUS; PET AB A new PET ligand, 3-fluoro-5-(2-(2-F-18-(fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile (F-18-SP203) can quantify metabotropic glutamate subtype 5 receptors (mGluR5) in human brain by a bolus injection and kinetic modeling. As an alternative approach to a bolus injection, binding can simply be measured as a ratio of tissue to metabolite-corrected plasma at a single time point under equilibrium conditions achieved by administering the radioligand with a bolus injection followed by a constant infusion. The purpose of this study was to validate the equilibrium method as an alternative to the standard kinetic method for measuring F-18-SP203 binding in the brain. Nine healthy subjects were injected with F-18-SP203 using a bolus plus constant infusion for 300 min. A single ratio of bolus-to-constant infusion (the activity of bolus equaled to that of infusion over 219 min) was applied to all subjects to achieve equilibrium in approximately 120 min. Ass measure of ligand binding, we compared total distribution volume (V-T) calculated by the equilibrium and kinetic methods in each scan. The equilibrium method calculated V-T by the ratio of radioactivity in the brain to the concentration of F-18-SP203 in arterial plasma at 120 min, and the kinetic method calculated V-T by a two-tissue compartment model using brain and plasma dynamic data from 0 to 120 min. V-T obtained via the equilibrium method was highly correlated with V-T obtained via kinetic modeling. Inter-subject variability of V-T obtained via the equilibrium method was slightly smaller than V-T obtained via the kinetic method. V-T obtained via the equilibrium method was -10% higher than V-T obtained via the kinetic method, indicating a small difference between the measurements. Taken together, the results of this study show that using the equilibrium method is an acceptable alternative to the standard kinetic method when using F-18-SP203 to measure mGluR5. Although small differences in the measurements obtained via the equilibrium and kinetic methods exist, both methods consistently measured mGluR5 as indicated by the highly correlated V-T values; the equilibrium method was slightly more precise, as indirectly measured by the smaller coefficient of variability across subjects. In addition, when using F-18-SP203, the equilibrium method is more efficient because it requires much less data. (C) 2011 Published by Elsevier Inc. C1 [Kimura, Yasuyuki; Simeon, Fabrice G.; Zoghbi, Sami S.; Zhang, Yi; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Hatazawa, Jun] Osaka Univ, Grad Sch Med, Dept Nucl Med & Tracer Kinet, Suita, Osaka 5650871, Japan. [Kimura, Yasuyuki] Natl Inst Radiol Sci, Mol Imaging Ctr, Chiba 2638555, Japan. RP Fujita, M (reprint author), NIMH, Mol Imaging Branch, 10 Ctr Dr,MSC 1026,Bldg 10,Rm B1D43, Bethesda, MD 20892 USA. EM y-kimura@nirs.go.jp; simeonf@mail.nih.gov; zoghbis@mail.nih.gov; yizhang@mail.nih.gov; hatazawa@tracer.med.osaka-u.ac.jp; pikev@mail.nih.gov; innisr@mail.nih.gov; fujitam@mail.nih.gov RI Kimura, Yasuyuki/D-4459-2016 OI Kimura, Yasuyuki/0000-0002-7927-9483 FU National Institute of Mental Health [Z01-MH-002795-07, Z01-MH-002852-04] FX This research was supported by the Intramural Program of the National Institute of Mental Health (projects Z01-MH-002795-07 and Z01-MH-002852-04). We thank Kacey Anderson, Leah P. Dickstein, Maria D. Ferraris Araneta, Gerald L Hodges, Kimberly Jenko, Nobuyo Kimura, William C. Kreisl, Barbara A. Scepura, Cheryl L. Wallisch, JeihSan Liow, Robert L Gladding, and the staff of the PET Department for successful completion of the studies, George J. Grimes, Judith M. Starling and Christine Y. Hon for their comments on adsorption of the ligand, David Luckenbaugh for his comments on the statistics, loline Henter for editorial assistance, and PMOD Technologies (Zurich, Switzerland) for providing its image analysis and modeling software. NR 13 TC 7 Z9 7 U1 0 U2 2 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 2124 EP 2130 DI 10.1016/j.neuroimage.2011.10.028 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 881NS UT WOS:000299494000015 PM 22032949 ER PT J AU Chen, R Resnick, SM Davatzikos, C Herskovits, EH AF Chen, Rong Resnick, Susan M. Davatzikos, Christos Herskovits, Edward H. TI Dynamic Bayesian network modeling for longitudinal brain morphometry SO NEUROIMAGE LA English DT Article DE Dynamic Bayesian network; Longitudinal morphometry ID MILD COGNITIVE IMPAIRMENT; VOXEL-BASED MORPHOMETRY; MCI; MRI; CONVERSION; ATROPHY; IMAGES; VOLUME; MAPS AB Identifying interactions among brain regions from structural magnetic-resonance images presents one of the major challenges in computational neuroanatomy. We propose a Bayesian data-mining approach to the detection of longitudinal morphological changes in the human brain. Our method uses a dynamic Bayesian network to represent evolving inter-regional dependencies. The major advantage of dynamic Bayesian network modeling is that it can represent complicated interactions among temporal processes. We validated our approach by analyzing a simulated atrophy study, and found that this approach requires only a small number of samples to detect the ground-truth temporal model. We further applied dynamic Bayesian network modeling to a longitudinal study of normal aging and mild cognitive impairment - the Baltimore Longitudinal Study of Aging. We found that interactions among regional volume-change rates for the mild cognitive impairment group are different from those for the normal-aging group. (C) 2011 Elsevier Inc. All rights reserved. C1 [Chen, Rong; Davatzikos, Christos; Herskovits, Edward H.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Resnick, Susan M.] NIA, NIH, Baltimore, MD 21224 USA. RP Chen, R (reprint author), Univ Penn, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. EM rong.chen@uphs.upenn.edu RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 FU National Institutes of Health [R01 AG13743, R03 EB-009310]; National Institute of Aging; National Institute of Mental Health; American Recovery and Reinvestment Act; [N01-AG-3-2124] FX This work was supported by National Institutes of Health grant R01 AG13743, which is funded by the National Institute of Aging, and the National Institute of Mental Health; this work was also supported by the American Recovery and Reinvestment Act. This work was supported by National Institutes of Health grant R03 EB-009310. This research was supported in part by the Intramural Research Program, National Institute on Aging. NIH and by research and development contract N01-AG-3-2124. NR 33 TC 15 Z9 15 U1 0 U2 4 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 2330 EP 2338 DI 10.1016/j.neuroimage.2011.09.023 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 881NS UT WOS:000299494000035 PM 21963916 ER PT J AU Zhang, J Laughon, SK Branch, DW AF Zhang, Jun Laughon, S. Katherine Branch, D. Ware TI Oxytocin Regimen for Labor Augmentation, Labor Progression, and Perinatal Outcomes Reply SO OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 [Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE Shanghai Key Lab Childrens Environm Hlth, Shanghai 200030, Peoples R China. [Laughon, S. Katherine] NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Branch, D. Ware] Intermt Healthcare, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Branch, D. Ware] Univ Utah, Salt Lake City, UT USA. RP Zhang, J (reprint author), Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE Shanghai Key Lab Childrens Environm Hlth, Shanghai 200030, Peoples R China. NR 2 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2012 VL 119 IS 2 BP 381 EP 382 PN 1 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 883AF UT WOS:000299604300030 ER PT J AU Leventhal, AM David, SP Brightman, M Strong, D McGeary, JE Brown, RA Lloyd-Richardson, EE Munafo, M Uhl, GR Niaura, R AF Leventhal, A. M. David, S. P. Brightman, M. Strong, D. McGeary, J. E. Brown, R. A. Lloyd-Richardson, E. E. Munafo, M. Uhl, G. R. Niaura, R. TI Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation SO PHARMACOGENOMICS JOURNAL LA English DT Article DE DRD4; VNTR; smoking cessation; bupropion ID DRD4 VNTR POLYMORPHISM; EXON-III POLYMORPHISM; TOBACCO DEPENDENCE; CIGARETTE-SMOKING; CLINICAL-TRIAL; D-4 RECEPTORS; ALCOHOL; ASSOCIATION; CUES; VARIANTS AB Smokers (>= 10 cigarettes per day, N = 331) of European ancestry taking part in a double-blind placebo-controlled randomized trial of 12 weeks of treatment with bupropion along with counseling for smoking cessation were genotyped for a variable number of tandem repeats polymorphism in exon III of the dopamine D4 receptor gene. Generalized estimating equations predicting point-prevalence abstinence at end of treatment and 2, 6 and 12 months after the end of treatment indicated that bupropion (vs placebo) predicted increased odds of abstinence. The main effect of Genotype was not significant. A Genotype x Treatment interaction (P = 0.005) showed that bupropion predicted increased odds of abstinence in long-allele carriers (odds ratios (OR) = 1.31, P < 0.0001), whereas bupropion was not associated with abstinence among short-allele homozygotes (OR = 1.06, P = 0.23). The Genotype x Treatment interaction remained when controlling for demographic and clinical covariates (P = 0.01) and in analyses predicting continuous abstinence (P's <= 0.054). Bupropion may be more efficacious for smokers who carry the long allele, which is relevant to personalized pharmacogenetic treatment approaches. The Pharmacogenomics Journal (2012) 12, 86-92; doi:10.1038/tpj.2010.64; published online 27 July 2010 C1 [Leventhal, A. M.; Brightman, M.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA. [David, S. P.] Stanford Univ, Sch Med, Dept Family & Community Med, Palo Alto, CA 94304 USA. [Strong, D.; McGeary, J. E.; Brown, R. A.] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Providence, RI 02912 USA. [Lloyd-Richardson, E. E.] Univ Massachusetts, Dept Psychol, Dartmouth, MA USA. [Munafo, M.] Univ Bristol, Dept Expt Psychol, Bristol, Avon, England. [Uhl, G. R.] Natl Inst Drug Abuse, Mol Neurobiol Res Branch, Intramural Res Program, Baltimore, MD USA. [Niaura, R.] Amer Legacy Fdn, Schroder Inst, Washington, DC USA. RP Leventhal, AM (reprint author), Univ So Calif, Dept Prevent Med, Keck Sch Med, 2250 Alcazar St,CSC 240, Los Angeles, CA 90033 USA. EM adam.leventhal@usc.edu OI David, Sean/0000-0002-4922-2603; Munafo, Marcus/0000-0002-4049-993X FU NIH [DA025041, HL32318, CA84719, DA08511, DA14276, DA27331]; NIDA-IRP FX This research was supported by NIH grants DA025041 (AML), HL32318 and CA84719 (RN), DA08511 (RAB), DA14276 and DA27331 (SPD) and NIDA-IRP. NR 43 TC 15 Z9 15 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD FEB PY 2012 VL 12 IS 1 BP 86 EP 92 DI 10.1038/tpj.2010.64 PG 7 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 884PE UT WOS:000299719200010 PM 20661272 ER PT J AU Miller, CM Rindflesch, TC Fiszman, M Hristovski, D Shin, D Rosemblat, G Zhang, H Strohl, KP AF Miller, Christopher M. Rindflesch, Thomas C. Fiszman, Marcelo Hristovski, Dimitar Shin, Dongwook Rosemblat, Graciela Zhang, Han Strohl, Kingman P. TI A Closed Literature-Based Discovery Technique Finds a Mechanistic Link Between Hypogonadism and Diminished Sleep Quality in Aging Men SO SLEEP LA English DT Article DE Information technology; literature-based discovery; testosterone; cortisol; sleep; men ID PITUITARY-ADRENAL AXIS; OLDER MEN; TESTOSTERONE LEVELS; HEALTHY-MEN; PLASMA TESTOSTERONE; CORTISOL SECRETION; CIRCADIAN-RHYTHM; SEX; HORMONE; ASSOCIATION AB Study Objectives: Sleep quality commonly diminishes with age, and, further, aging men often exhibit a wider range of sleep pathologies than women. We used a freely available, web-based discovery technique (Semantic MEDLINE) supported by semantic relationships to automatically extract information from MEDLINE titles and abstracts. Design: We assumed that testosterone is associated with sleep (the A-C relationship in the paradigm) and looked for a mechanism to explain this association (B explanatory link) as a potential or partial mechanism underpinning the etiology of eroded sleep quality in aging men. Measurements and Results: Review of full-text papers in critical nodes discovered in this manner resulted in the proposal that testosterone enhances sleep by inhibiting cortisol. Using this discovery method, we posit, and could confirm as a novel hypothesis, cortisol as part of a mechanistic link elucidating the observed correlation between decreased testosterone in aging men and diminished sleep quality. Conclusions: This approach is publically available and useful not only in this manner but also to generate from the literature alternative explanatory models for observed experimental results. C1 [Miller, Christopher M.] NIH, Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Cognit Sci Branch, Bethesda, MD 20894 USA. [Strohl, Kingman P.] Louis Stokes Cleveland DVA Med Ctr, Case Sch Med, Div Pulm Crit Care & Sleep Med, Cleveland, OH USA. [Strohl, Kingman P.] Univ Ljubljana Fac Med, Inst Biomed Informat, Ljubljana, Slovenia. [Zhang, Han] China Med Univ, Dept Med Informat, Shenyang, Peoples R China. RP Miller, CM (reprint author), NIH, Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Cognit Sci Branch, Bldg 38A,Rm B1N-28C,MSC 3841, Bethesda, MD 20894 USA. EM millercm@mail.nih.gov OI Hristovski, Dimitar/0000-0001-6908-0246 FU National Institutes of Health, National Library of Medicine FX This study was supported in part by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. The seventh author was supported by an appointment to the National Library of Medicine Research Participation Program administered by the Oak Ridge Institute for Science and Education through an inter-agency agreement between the U. S. Department of Energy and the National Library of Medicine. For access to Semantic MEDLINE, send email to trindflesch@mail.nih.gov. Research carried out at National Institutes of Health, National Library of Medicine, Lister Hill National Center for Biomedical Communications, Bethesda, MD 20894. NR 60 TC 16 Z9 17 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD FEB 1 PY 2012 VL 35 IS 2 BP 279 EP 285 DI 10.5665/sleep.1640 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 885LF UT WOS:000299779800016 PM 22294819 ER PT J AU Matthews, CE George, SM Moore, SC Bowles, HR Blair, A Park, Y Troiano, RP Hollenbeck, A Schatzkin, A AF Matthews, Charles E. George, Stephanie M. Moore, Steven C. Bowles, Heather R. Blair, Aaron Park, Yikyung Troiano, Richard P. Hollenbeck, Albert Schatzkin, Arthur TI Amount of time spent in sedentary behaviors and cause-specific mortality in US adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID TELEVISION VIEWING TIME; CARDIOVASCULAR-DISEASE MORTALITY; PHYSICAL-ACTIVITY; PLASMA-GLUCOSE; UNITED-STATES; LEISURE-TIME; SITTING-TIME; OLDER-ADULTS; ALL-CAUSE; WOMEN AB Background: Sedentary behaviors predominate modern life, yet we do not fully understand the adverse effects of these behaviors on mortality after considering the benefits of moderate-vigorous physical activity (MVPA). Objective: We tested the hypotheses that higher amounts of overall sitting time and television viewing are positively associated with mortality and described the independent and combined effects of these sedentary behaviors and MVPA on mortality. Design: In the NIH-AARP Diet and Health Study, we examined 240,819 adults (aged 50-71 y) who did not report any cancer, cardiovascular disease, or respiratory disease at baseline. Mortality was ascertained over 8.5 y. Results: Sedentary behaviors were positively associated with mortality after adjustment for age, sex, education, smoking, diet, race, and MVPA. Participants who reported the most television viewing (>= 7 h compared with <1 h/d) were at greater risk of all-cause (HR: 1.61; 95% CI: 1.47, 1.76), cardiovascular (HR: 1.85; 95% CI: 1.56, 2.20), and cancer (HR: 1.22; 95% CI: 1.06, 1.40) mortality after adjustment for MVPA. Overall sitting was associated with all-cause mortality. Even among adults reporting high levels of MVPA (>7 h/wk), high amounts of television viewing (>= 7 h/d) remained associated with increased risk of all-cause (HR: 1.47; 95% CI: 1.20, 1.79) and cardiovascular (HR: 2.00; 95% CI: 1.33, 3.00) mortality compared with those reporting the least television viewing (<1 h/d). Conclusions: Time spent in sedentary behaviors was positively associated with mortality, and participation in high levels of MVPA did not fully mitigate health risks associated with prolonged time watching television. Adults should be encouraged to reduce time spent in sedentary behaviors, when possible, and to participate in MVPA at recommended levels. The NIH-AARP Diet and Health Study was registered at clinicaltrials.gov as NCT00340015. Ant J Clin Nutr 2012;95:437-45. C1 [Matthews, Charles E.; George, Stephanie M.; Moore, Steven C.; Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Blair, Aaron] NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Bowles, Heather R.; Troiano, Richard P.] NCI, Risk Factor Monitoring & Methods Branch, Div Canc Control & Populat Sci, Rockville, MD USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Matthews, CE (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 3028, Bethesda, MD 20892 USA. EM charles.matthews2@nih.gov RI matthews, Charles/E-8073-2015; Moore, Steven/D-8760-2016; OI matthews, Charles/0000-0001-8037-3103; Moore, Steven/0000-0002-8169-1661; Troiano, Richard/0000-0002-6807-989X; Park, Yikyung/0000-0002-6281-489X FU NIH, National Cancer Institute FX Supported in part by the Intramural Research Program of the NIH, National Cancer Institute. NR 37 TC 212 Z9 216 U1 3 U2 55 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 437 EP 445 DI 10.3945/ajcn.111.019620 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 883QC UT WOS:000299647800023 PM 22218159 ER PT J AU Bowers, K Tobias, DK Yeung, E Hu, FB Zhang, CL AF Bowers, Katherine Tobias, Deirdre K. Yeung, Edwina Hu, Frank B. Zhang, Cuilin TI A prospective study of prepregnancy dietary fat intake and risk of gestational diabetes SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID GLUCOSE-TOLERANCE; CHOLESTEROL INTAKE; BETA-CELL; MELLITUS; WOMEN; PREGNANCY; HYPERGLYCEMIA AB Background: Fatty acids play a vital role in glucose homeostasis; however, studies on habitual dietary fat intakes and gestational diabetes mellitus (GDM) risk are limited and provide conflicting findings. Objective: We determined whether the total amount and the type and source of prepregnancy dietary fats are related to risk of GDM. Design: A prospective study was conducted in 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses' Health Study II. In these women, 860 incident GDM cases were reported. The adjusted RR of GDM was estimated for quintiles of total fat, specific fat, and the source of fat intakes by pooled logistic regression. Results: Higher animal fat and cholesterol intakes were significantly associated with increased GDM risk. Across increasing quintiles of animal fat, RRs (95% CIs) for GDM were 1.00 (reference), 1.55 (1.20, 1.98), 1.43 (1.09, 1.88), 1.40 (1.04, 1.89), and 1.88 (1.36, 2.60) (P-trend = 0.05). Corresponding RRs (95% CIs) for dietary cholesterol were 1.00 (reference), 1.08 (0.84, 1.32), 1.02 (0.78, 1.29), 1.20 (0.93, 1.55), and 1.45 (1.11, 1.89) (P-trend = 0.04). The substitution of 5% of energy from animal fat for an equal percentage of energy from carbohydrates was associated with significantly increased risk of GDM [RR (95% CI): 1.13 (1.08, 1.18); P < 0.0001]. No significant associations were observed between dietary polyunsaturated fat, monounsaturated fat, or trans fat intakes and GDM risk. Conclusion: Higher prepregnancy intakes of animal fat and cholesterol were associated with elevated GDM risk. Am J Clin Nutr 2012;95:446-53. C1 [Bowers, Katherine; Yeung, Edwina; Zhang, Cuilin] Eunice Kennedy Shrive Natl Inst Child Hlth & Huma, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Tobias, Deirdre K.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tobias, Deirdre K.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hu, Frank B.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Hu, Frank B.] Harvard Univ, Sch Med, Boston, MA USA. RP Zhang, CL (reprint author), Eunice Kennedy Shrive Natl Inst Child Hlth & Huma, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM bowerska2@mail.nih.gov; zhangcu@mail.nih.gov RI Yeung, Edwina/F-5992-2015; Bowers, Katherine/N-5226-2015 OI Yeung, Edwina/0000-0002-3851-2613; FU NIH [CA50385, DK58845]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH FX Supported by research grants CA50385 and DK58845 from the NIH and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH (KB, CZ, and EY). NR 34 TC 29 Z9 30 U1 0 U2 8 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 446 EP 453 DI 10.3945/ajcn.111.026294 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 883QC UT WOS:000299647800024 PM 22218158 ER PT J AU Schliep, KC Schisterman, EF Mumford, SL Pollack, AZ Zhang, CL Ye, AJ Stanford, JB Hammoud, AO Porucznik, CA Wactawski-Wende, J AF Schliep, Karen C. Schisterman, Enrique F. Mumford, Sunni L. Pollack, Anna Z. Zhang, Cuilin Ye, Aijun Stanford, Joseph B. Hammoud, Ahmad O. Porucznik, Christina A. Wactawski-Wende, Jean TI Caffeinated beverage intake and reproductive hormones among premenopausal women in the BioCycle Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; MARGINAL STRUCTURAL MODELS; EPITHELIAL OVARIAN-CANCER; MENSTRUAL-CYCLE; GENETIC POLYMORPHISMS; PERIMENOPAUSAL WOMEN; BINDING GLOBULIN; CYP1A2 GENOTYPE; ESTROGEN-LEVELS; BREAST-CANCER AB Background: Caffeinated beverages are widely consumed among women of reproductive age, but their association with reproductive hormones, and whether race modifies any such associations, is not well understood. Objective: We assessed the relation between caffeine and caffeinated beverage intake and reproductive hormones in healthy premenopausal women and evaluated the potential effect modification by race. Design: Participants (n = 259) were followed for up to 2 menstrual cycles and provided fasting blood specimens for hormonal assessment at up to 8 visits per cycle and four 24-h dietary recalls per cycle. Weighted linear mixed models and nonlinear mixed models with harmonic terms were used to estimate associations between caffeine and hormone concentrations, adjusted for age, adiposity, physical activity, energy and alcohol intakes, and perceived stress. On the basis of a priori assumptions, an interaction between race and caffeine was tested, and stratified results are presented. Results: Caffeine intake >= 200 mg/d was inversely associated with free estradiol concentrations among white women (beta = -0.15; 95% CI: -0.26, -0.05) and positively associated among Asian women (beta = 0.61; 95% CI: 0.31, 0.92). Caffeinated soda intake and green tea intake >= 1 cup/d (1 cup = 240 mL) were positively associated with free estradiol concentrations among all races: beta = 0.14 (95% CI: 0.06, 0.22) and beta = 0.26 (95% CI: 0.07, 0.45), respectively. Conclusions: Moderate consumption of caffeine was associated with reduced estradiol concentrations among white women, whereas caffeinated soda and green tea intakes were associated with increased estradiol concentrations among all races. Further research is warranted on the association between caffeine and caffeinated beverages and reproductive hormones and whether these relations differ by race. Am J Clin Nutr 2012;95:488-97. C1 [Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. [Schliep, Karen C.; Stanford, Joseph B.; Porucznik, Christina A.] Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT USA. [Hammoud, Ahmad O.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,7B03M, Rockville, MD 20852 USA. EM schistee@mail.nih.gov OI Pollack, Anna/0000-0002-4313-3298; Schisterman, Enrique/0000-0003-3757-641X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. NR 59 TC 15 Z9 15 U1 1 U2 11 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2012 VL 95 IS 2 BP 488 EP 497 DI 10.3945/ajcn.111.021287 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 883QC UT WOS:000299647800029 PM 22237060 ER PT J AU Tembhare, P Yuan, CM Morris, JC Janik, JE Filie, AC Stetler-Stevenson, M AF Tembhare, Prashant Yuan, Constance M. Morris, John C. Janik, John E. Filie, Armando C. Stetler-Stevenson, Maryalice TI Flow Cytometric Immunophenotypic Assessment of T-Cell Clonality by V-beta Repertoire Analysis in Fine-Needle Aspirates and Cerebrospinal Fluid SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE T-cell clonality; Flow cytometry; V-beta repertoire; Cerebrospinal fluid; Fine-needle aspirate ID LEPTOMENINGEAL DISEASE; RECURRENT LYMPHOMA; DIAGNOSIS; LEUKEMIA/LYMPHOMA; CYTOMORPHOLOGY; CLASSIFICATION; INVOLVEMENT; NEOPLASMS; SPECIMENS; THERAPY AB Flow cytometric T-cell receptor V-beta repertoire analysis (TCR-V-beta-R) is a sensitive method to detect T-cell clonality; however, its implementation in low-cellularity specimens has not been established. We developed a strategy to use TCR-V-beta-R in cerebrospinal fluid (CSF) and fine-needle aspirate (FNA) specimens. Initially, full TCR-V-beta-R was evaluated in diagnostic/screening specimens from 8 patients with T-cell neoplasia to determine tumor-specific TCR-V-beta protein expression. Subsequently, an abbreviated, patient-specific TCR-V-beta-R evaluation was performed in 17 paucicellular specimens from the patients (8 CSF, 9 FNA) for staging and monitoring of minimal residual disease (MRD). A single cocktail containing 3 anti-V-beta antibodies (1 tumor-specific and 2 negative controls) in combination with other antibodies chosen to help gate on atypical T cells is highly sensitive and specific for detecting low-level neoplastic T-cell involvement in paucicellular specimens. This TCR-V-beta-R strategy is valuable in staging and evaluating MRD in patients with T-cell non-Hodgkin lymphoma. C1 [Tembhare, Prashant; Yuan, Constance M.; Stetler-Stevenson, Maryalice] NCI, Flow Cytometry Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Filie, Armando C.] NCI, Cytopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Morris, John C.; Janik, John E.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, Flow Cytometry Unit, Pathol Lab, NIH, Bldg 10,Room 2A-33,Mail Stop 1500, Bethesda, MD 20892 USA. FU National Cancer Institute, National Institutes of Health, Bethesda, MD FX Supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Bethesda, MD. NR 25 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD FEB PY 2012 VL 137 IS 2 BP 220 EP 226 DI 10.1309/AJCPPT93VZMAREHK PG 7 WC Pathology SC Pathology GA 881KZ UT WOS:000299484900008 PM 22261447 ER PT J AU Boghossian, NS Horbar, JD Murray, JC Carpenter, JH AF Boghossian, Nansi S. Horbar, Jeffrey D. Murray, Jeffrey C. Carpenter, Joseph H. CA Vermont Oxford Network TI Anthropometric charts for infants with trisomies 21, 18, or 13 born between 22 weeks gestation and term: The VON charts SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE trisomy 21; trisomy 18; trisomy 13; Down syndrome; Edward syndrome; Patau syndrome; autosomal trisomies; growth curves; neonatal anthropometric charts; intrauterine growth; weight for gestational age; head circumference for gestational age ID BIRTH-WEIGHT; DOWNS-SYNDROME; INTRAUTERINE GROWTH; HEAD CIRCUMFERENCE; AGE; CHILDREN; MORTALITY; FETUSES; PREVALENCE; CURVES AB Data on birth weight for gestational age (GA) are not well described for infants with trisomy 21 (T21), trisomy 18 (T18), or trisomy 13 (T13). We report on anthropometric charts of infants with these conditions using data from the Vermont Oxford Network (VON). Data from a total of 5,147 infants with T21 aged 2241 weeks, 1,053 infants with T18 aged 2241 weeks, and 613 infants with T13 aged 2240 weeks were used to create birth weight for GA charts. Head circumference for GA charts were created for infants with T21 only. Combined-sex charts were generated for infants with T18 or T13 while sex-specific charts were generated for infants with T21. Smoothed centiles were created using LmsChartMaker Pro 2.3. Among the three examined groups, infants with T18 were the most likely to be growth restricted while infants with T21 were the least likely to be growth restricted. The new charts for infants with T21 were also compared to the Lubchenco and Fenton charts and both show frequent misclassification of infants with T21 as small or large for GA. The new charts should prove to be useful, especially for infants with T21, to assist in medical management and guide nutrition care decisions. (C) 2012 Wiley Periodicals, Inc. C1 [Boghossian, Nansi S.; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Horbar, Jeffrey D.; Carpenter, Joseph H.; Vermont Oxford Network] Vermont Oxford Network, Burlington, VT USA. [Horbar, Jeffrey D.] Univ Vermont, Dept Pediat, Burlington, VT USA. RP Boghossian, NS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, 6100 Execut Blvd,Room 7B03C, Bethesda, MD 20892 USA. EM nansi.boghossian@nih.gov FU Vermont Oxford Network FX Conflict of interest: Dr. Horbar is the Chief Executive and Scientific Officer of the Vermont Oxford Network. Mr. Carpenter is the Director of Operations and Statistics at the Vermont Oxford Network. Both receive salary from the Vermont Oxford Network. None of the authors have disclosures to report. NR 31 TC 8 Z9 8 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD FEB PY 2012 VL 158A IS 2 BP 322 EP 332 DI 10.1002/ajmg.a.34423 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 879LY UT WOS:000299331900008 PM 22246859 ER PT J AU Friedman, A Robbins, E Wendler, D AF Friedman, Alexander Robbins, Emily Wendler, David TI WHICH BENEFITS OF RESEARCH PARTICIPATION COUNT AS 'DIRECT'? SO BIOETHICS LA English DT Article DE direct benefits; fallacy of the package deal; informed consent; vulnerable subjects AB It is widely held that individuals who are unable to provide informed consent should be enrolled in clinical research only when the risks are low, or the research offers them the prospect of direct benefit. There is now a rich literature on when the risks of clinical research are low enough to enroll individuals who cannot consent. Much less attention has focused on which benefits of research participation count as direct, and the few existing accounts disagree over how this crucial concept should be defined. This disagreement raises concern over whether those who cannot consent, including children and adults with severe dementia, are being adequately protected. The present paper attempts to address this concern by considering first what additional protections are needed for these vulnerable individuals. This analysis suggests that the extant definitions of direct benefits either provide insufficient protection for research subjects or pose excessive obstacles to appropriate research. This analysis also points to a modified definition of direct benefits with the potential to avoid these two extremes, protecting individuals who cannot consent without blocking appropriate research. C1 [Wendler, David] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Ctr Clin, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 20 TC 9 Z9 9 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-9702 J9 BIOETHICS JI Bioethics PD FEB PY 2012 VL 26 IS 2 BP 60 EP 67 DI 10.1111/j.1467-8519.2010.01825.x PG 8 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 878JG UT WOS:000299252300002 PM 20497168 ER PT J AU Sun, W Liu, KL Ryu, H Kang, DW Kim, YS Kim, MS Cho, Y Bhondwe, RS Thorat, SA Kim, HS Pearce, LV Pavlyukovets, VA Tran, R Morgan, MA Lazar, J Ryder, CB Toth, A Blumberg, PM Lee, J AF Sun, Wei Liu, Keliang Ryu, HyungChul Kang, Dong Wook Kim, Yong Soo Kim, Myeong Seop Cho, Yongsung Bhondwe, Rahul S. Thorat, Shivaji A. Kim, Ho Shin Pearce, Larry V. Pavlyukovets, Vladimir A. Tran, Richard Morgan, Matthew A. Lazar, Jozsef Ryder, Christopher B. Toth, Attila Blumberg, Peter M. Lee, Jeewoo TI 2-(4-Methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure-activity relationships in the B and C-regions SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE TRPV1 antagonists; Analgesic; Capsaicin; Resiniferatoxin ID VANILLOID RECEPTOR; CAPSAICIN RECEPTORS; ANALOGS; POTENT; AGONISTS; CHANNEL AB On the basis of the previous lead N-4-t-butylbenzyl 2-(3-fluoro-4-methylsulfonylaminophenyl) propanamide (3) as a potent TRPV1 antagonist, structure-activity relationships for the B (propanamide part) and C-region (4-t-butylbenzyl part) have been investigated for rTRPV1 in CHO cells. The B-region was modified with dimethyl, cyclopropyl and reverse amides and then the C-region was replaced with 4-substituted phenyl, aryl alkyl and diaryl alkyl derivatives. Among them, compound 50 showed high binding affinity with K-i = 21.5 nM, which was twofold more potent than 3 and compound 54 exhibited potent antagonism with K-i(ant) = 8.0 nM comparable to 3. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Ryu, HyungChul; Kang, Dong Wook; Kim, Yong Soo; Kim, Myeong Seop; Cho, Yongsung; Bhondwe, Rahul S.; Thorat, Shivaji A.; Kim, Ho Shin; Lee, Jeewoo] Seoul Natl Univ, Med Chem Lab, Pharmaceut Sci Res Inst, Coll Pharm, Seoul 151742, South Korea. [Sun, Wei; Liu, Keliang] Shenyang Pharmaceut Univ, Shenyang 110016, Liaoning, Peoples R China. [Pearce, Larry V.; Pavlyukovets, Vladimir A.; Tran, Richard; Morgan, Matthew A.; Lazar, Jozsef; Ryder, Christopher B.; Toth, Attila; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Med Chem Lab, Pharmaceut Sci Res Inst, Coll Pharm, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr RI Toth, Attila/F-4859-2010 OI Toth, Attila/0000-0001-6503-3653 FU National Research Foundation of Korea (NRF) [R11-2007-107-02001-0]; National Institutes of Health, Center for Cancer Research, National Cancer Institute [Z1A BC 005270] FX This research was supported by Research Funding from Digital-biotech, Grants R11-2007-107-02001-0 from the National Research Foundation of Korea (NRF), and the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute (Z1A BC 005270). We thank multiple additional fellows for technical assistance. NR 21 TC 2 Z9 2 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD FEB 1 PY 2012 VL 20 IS 3 BP 1310 EP 1318 DI 10.1016/j.bmc.2011.12.014 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 882BE UT WOS:000299535400017 PM 22227463 ER PT J AU Enewold, L Zhou, J McGlynn, KA Anderson, WF Shriver, CD Potter, JF Zahm, SH Zhu, KM AF Enewold, Lindsey Zhou, Jing McGlynn, Katherine A. Anderson, William F. Shriver, Craig D. Potter, John F. Zahm, Shelia H. Zhu, Kangmin TI Racial variation in breast cancer treatment among Department of Defense beneficiaries SO CANCER LA English DT Article ID AFRICAN-AMERICAN PATIENTS; BLACK-AND-WHITE; DISPARITIES; CARE; WOMEN; CARCINOMA; MORTALITY; OPPORTUNITIES; CHEMOTHERAPY; POPULATION AB BACKGROUND: Although the overall age-adjusted incidence rates for female breast cancer are higher among whites than blacks, mortality rates are higher among blacks. Many attribute this discrepancy to disparities in health care access and to blacks presenting with later stage disease. Within the Department of Defense (DoD) Military Health System, all beneficiaries have equal access to health care. The aim of this study was to determine whether female breast cancer treatment varied between white and black patients in the DoD system. METHODS: The study data were drawn from the DoD cancer registry and medical claims databases. Study subjects included 2308 white and 391 black women diagnosed with breast cancer between 1998 and 2000. Multivariate logistic regression analyses that controlled for demographic factors, tumor characteristics, and comorbidities were used to assess racial differences in the receipt of surgery, chemotherapy, and hormonal therapy. RESULTS: There was no significant difference in surgery type, particularly when mastectomy was compared with breast-conserving surgery plus radiation (blacks vs whites: odds ratio [OR], 1.1; 95% confidence interval [CI], 0.8-1.5). Among those with local stage tumors, blacks were as likely as whites to receive chemotherapy (OR, 1.2; 95% CI, 0.9-1.7) and hormonal therapy (OR, 1.0; 95% CI, 0.6-1.4). Among those with regional stage tumors, blacks were significantly less likely than whites to receive chemotherapy (OR, 0.4; 95% CI, 0.2-0.7) and hormonal therapy (OR, 0.5; 95% CI, 0.3-0.8). CONCLUSIONS: Even within an equal access health care system, stage-related racial variations in breast cancer treatment are evident. Studies that identify driving factors behind these within-stage racial disparities are warranted. Cancer 2012; 118: 812-20. (C) 2011 American Cancer Society. C1 [Enewold, Lindsey; Zhou, Jing; Shriver, Craig D.; Potter, John F.; Zhu, Kangmin] Walter Reed Army Med Ctr, US Mil Canc Inst, Washington, DC 20307 USA. [McGlynn, Katherine A.; Anderson, William F.; Zahm, Shelia H.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Shriver, Craig D.] Walter Reed Army Med Ctr, Dept Surg, Div Surg Oncol, Washington, DC 20307 USA. [Potter, John F.; Zhu, Kangmin] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. RP Enewold, L (reprint author), Walter Reed Army Med Ctr, US Mil Canc Inst, Bldg 1,Suite E-111,6900 Georgia Ave, Washington, DC 20307 USA. EM Lindsey.Enewold@us.army.mil RI Zahm, Shelia/B-5025-2015 FU United States Military Cancer Institute (USMCI) via the Uniformed Services University of the Health Sciences under the auspices of the Henry M. Jackson Foundation for the Advancement of Military Medicine; Walter Reed Army Medical Center; Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute, National Institutes of Health FX Supported by the United States Military Cancer Institute (USMCI) via the Uniformed Services University of the Health Sciences under the auspices of the Henry M. Jackson Foundation for the Advancement of Military Medicine; the Clinical Breast Care Project, Walter Reed Army Medical Center; and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute, National Institutes of Health. The original data linkage was supported by the USMCI and DCEG. NR 29 TC 12 Z9 12 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 812 EP 820 DI 10.1002/cncr.26346 PG 9 WC Oncology SC Oncology GA 879NB UT WOS:000299335500027 PM 21766298 ER PT J AU Zhao, XZ Maddali, K Metifiot, M Smith, SJ Vu, BC Marchand, C Hughes, SH Pommier, Y Burke, TR AF Zhao, Xue Zhi Maddali, Kasthuraiah Metifiot, Mathieu Smith, Steven J. Vu, B. Christie Marchand, Christophe Hughes, Stephen H. Pommier, Yves Burke, Terrence R., Jr. TI Bicyclic Hydroxy-1H-pyrrolopyridine-trione Containing HIV-1 Integrase Inhibitors SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE drug discovery; mechanism-based drug design; nonpeptide ID DEPROTONATION-CYCLOADDITION CASCADE; RALTEGRAVIR; RESISTANCE; DISCOVERY; INFECTION; POTENT; IMIDOSULFOXIDES; ELVITEGRAVIR AB HIV-1 integrase (IN) is a validated therapeutic target for the treatment of AIDS. However, the emergence of resistance to raltegravir, the sole marketed FDA-approved IN inhibitor, emphasizes the need to develop second-generation inhibitors that retain efficacy against clinically relevant IN mutants. We report herein bicyclic hydroxy-1H-pyrrolopyridine-triones as a new family of HIV-1 integrase inhibitors that were efficiently prepared using a key Pummerer cyclization deprotonation cycloaddition cascade of imidosulfoxides. In in vitro HIV-1 integrase assays, the analogs showed low micromolar inhibitory potencies with selectivity for strand transfer reactions as compared with 3'-processing inhibition. A representative inhibitor (5e) retained most of its inhibitory potency against the three major raltegravir-resistant IN mutant enzymes, G140S/Q148H, Y143R, and N155H. In antiviral assays employing viral vectors coding these IN mutants, compound 5e was approximately 200- and 20-fold less affected than raltegravir against the G140S/Q148H and Y143R mutations, respectively. Against the N155H mutation, 5e was approximately 10-fold less affected than raltegravir. Thus, our new compounds represent a novel structural class that may be further developed to overcome resistance to raltegravir, particularly in the case of the G140S/Q148H mutations. C1 [Zhao, Xue Zhi; Burke, Terrence R., Jr.] NCI, Chem Biol Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA. [Maddali, Kasthuraiah; Metifiot, Mathieu; Marchand, Christophe; Pommier, Yves] NCI, Lab Mol Pharmacol, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Smith, Steven J.; Vu, B. Christie; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Zhao, XZ (reprint author), NCI, Chem Biol Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA. EM xuezhi.zhao@nih.gov; tburke@helix.nih.gov RI Zhao, Xue Zhi/N-9594-2014; Burke, Terrence/N-2601-2014 OI Zhao, Xue Zhi/0000-0003-1006-6364; FU NIH, Center for Cancer Research, NCI-Frederick; National Cancer Institute, National Institutes of Health; Joint Science and Technology Office of the Department of Defense FX This work was supported in part by the Intramural Research Program of the NIH, Center for Cancer Research, NCI-Frederick and the National Cancer Institute, National Institutes of Health and the Joint Science and Technology Office of the Department of Defense. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 26 TC 10 Z9 11 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-0277 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD FEB PY 2012 VL 79 IS 2 BP 157 EP 165 DI 10.1111/j.1747-0285.2011.01270.x PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 872WP UT WOS:000298841400002 PM 22107736 ER PT J AU Vandenberg, LN Chahoud, I Heindel, JJ Padmanabhan, V Paumgartten, FJR Schoenfelder, G AF Vandenberg, Laura N. Chahoud, Ibrahim Heindel, Jerrold J. Padmanabhan, Vasantha Paumgartten, Francisco J. R. Schoenfelder, Gilbert TI Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A SO CIENCIA & SAUDE COLETIVA LA English DT Review DE Endocrine disruptor; Human exposure; PBPK/PBTK model; Pregnancy; Risk assessment; Toxicokinetics ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; TANDEM MASS-SPECTROMETRY; HPLC-MS/MS METHOD; ENVIRONMENTAL PHENOLS; ESTROGEN-RECEPTOR; ADIPOSE-TISSUE; HUMAN SERUM; FLUORESCENCE DETECTION; DISRUPTING CHEMICALS AB Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes. C1 [Vandenberg, Laura N.] Tufts Univ, Dept Biol, Tufts Ctr Regenerat & Dev Biol, Medford, MA 02155 USA. [Chahoud, Ibrahim] Charite, Inst Klin Pharmakol & Toxikol, D-13353 Berlin, Germany. [Heindel, Jerrold J.] Natl Inst Environm Hlth Sci, Div Extramural Res & Training, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Padmanabhan, Vasantha] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Paumgartten, Francisco J. R.] Fundacao Oswaldo Cruz, Natl Sch Publ Hlth, Lab Environm Toxicol, Rio De Janeiro, Brazil. [Schoenfelder, Gilbert] Univ Wurzburg, Inst Pharmacol & Toxicol, Wurzburg, Germany. RP Vandenberg, LN (reprint author), Tufts Univ, Dept Biol, Tufts Ctr Regenerat & Dev Biol, 200 Boston Ave,Suite 4600, Medford, MA 02155 USA. EM laura.vandenberg@tufts.edu RI Padmanabhan, Vasantha/C-8558-2017; OI Padmanabhan, Vasantha/0000-0002-8443-7212; Schonfelder, Gilbert/0000-0001-6134-1990 NR 128 TC 57 Z9 58 U1 3 U2 56 PU ABRASCO PI RIO DE JANEIRO PA RUA HESPERIA, 16-PARTE MANGUINHOS, RIO DE JANEIRO, 21050-040, BRAZIL SN 1413-8123 J9 CIENC SAUDE COLETIVA JI Cienc. Saude Coletiva PD FEB PY 2012 VL 17 IS 2 BP 407 EP 434 PG 28 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 880CX UT WOS:000299383400016 PM 22267036 ER PT J AU Wynn, JL Tan, S Gantz, MG Das, A Goldberg, RN Adams-Chapman, I Stoll, BJ Shankaran, S Walsh, MC Auten, KJ Miller, NA Sanchez, PJ Higgins, RD Cotten, CM Smith, PB Benjamin, DK AF Wynn, James L. Tan, Sylvia Gantz, Marie G. Das, Abhik Goldberg, Ronald N. Adams-Chapman, Ira Stoll, Barbara J. Shankaran, Seetha Walsh, Michele C. Auten, Kathy J. Miller, Nancy A. Sanchez, Pablo J. Higgins, Rosemary D. Cotten, C. Michael Smith, P. Brian Benjamin, Daniel K., Jr. CA NICHD Neonatal Res Network TI Outcomes Following Candiduria in Extremely Low Birth Weight Infants SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID NEONATAL RESEARCH NETWORK; URINARY-TRACT-INFECTION; INTENSIVE-CARE-UNIT; FUNGAL-INFECTION; PRETERM INFANTS; RISK-FACTORS; CANDIDIASIS; SEPSIS AB Background. Candidiasis carries a significant risk of death or neurodevelopmental impairment (NDI) in extremely low birth weight infants (ELBW; < 1000 g). We sought to determine the impact of candiduria in ELBW preterm infants. Methods. Our study was a secondary analysis of the Neonatal Research Network study Early Diagnosis of Nosocomial Candidiasis. Follow-up assessments included Bayley Scales of Infant Development examinations at 18-22 months of corrected age. Risk factors were compared between groups using exact tests and general linear modeling. Death, NDI, and death or NDI were compared using generalized linear mixed modeling. Results. Of 1515 infants enrolled, 34 (2.2%) had candiduria only. Candida was isolated from blood only (69 of 1515 [4.6%]), cerebrospinal fluid (CSF) only (2 of 1515 [0.1%]), other sterile site only (not urine, blood, or CSF; 4 of 1515 [0.3%]), or multiple sources (28 of 1515 [2%]). Eleven infants had the same Candida species isolated in blood and urine within 3 days; 3 (27%) had a positive urine culture result first. Most urine isolates were Candida albicans (21 of 34 [62%]) or Candida parapsilosis (7 of 34 [29%]). Rate of death or NDI was greater among those with candiduria (50%) than among those with suspected but not proven infection (32%; odds ratio, 2.5 [95% confidence interval, 1.2-5.3]) after adjustment. No difference in death and death or NDI was noted between infants with candiduria and those with candidemia. Conclusions. These findings provide compelling evidence that ELBW infants with candiduria are at substantial risk of death or NDI. Candiduria in ELBW preterm infants should prompt a systemic evaluation (blood, CSF, and abdominal ultrasound) for disseminated Candida infection and warrants treatment. C1 [Benjamin, Daniel K., Jr.] Duke Univ, Dept Pediat, Duke Clin Res Inst, Durham, NC 27715 USA. [Tan, Sylvia; Gantz, Marie G.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. [Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA. [Adams-Chapman, Ira; Stoll, Barbara J.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. [Miller, Nancy A.; Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Benjamin, DK (reprint author), Duke Univ, Dept Pediat, Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27715 USA. EM danny.benjamin@duke.edu RI Smith, Phillip/I-5565-2014 FU ASPE HHS [1R18AE000028-01]; NCATS NIH HHS [UL1 TR000454]; NCRR NIH HHS [M01 RR007122, M01 RR008084, UL1 RR024139, UL1 RR024160, UL1 RR025008]; NICHD NIH HHS [U10 HD021364, 1K23HD060040-01, HD-044799-03, K23 HD044799, K23 HD060040, K24 HD058735, U10 HD021373, U10 HD021385, U10 HD021397, U10 HD027851, U10 HD027853, U10 HD027856, U10 HD027871, U10 HD027880, U10 HD027904, U10 HD034216, U10 HD036790, U10 HD040461, U10 HD040492, U10 HD040498, U10 HD040521, U10 HD040689, U10 HD053089, U10 HD053109, U10 HD053119, U10 HD40492] NR 21 TC 14 Z9 14 U1 0 U2 5 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 331 EP 339 DI 10.1093/cid/cir800 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 876SM UT WOS:000299128000010 PM 22144537 ER PT J AU Besson, GJ McMahon, D Maldarelli, F Mellors, JW AF Besson, Guillaume J. McMahon, Deborah Maldarelli, Frank Mellors, John W. TI Short-Course Raltegravir Intensification Does Not Increase 2 Long Terminal Repeat Episomal HIV-1 DNA in Patients on Effective Antiretroviral Therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID VIREMIA C1 [Besson, Guillaume J.; McMahon, Deborah; Mellors, John W.] Univ Pittsburgh, Div Infect Dis, Sch Med, Pittsburgh, PA 15261 USA. [Maldarelli, Frank] NCI, Frederick, MD 21701 USA. RP Mellors, JW (reprint author), Univ Pittsburgh, Div Infect Dis, Sch Med, 818 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM jwm1@pitt.edu FU PHS HHS [25XS119] NR 7 TC 22 Z9 22 U1 1 U2 3 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 451 EP 453 DI 10.1093/cid/cir721 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 876SM UT WOS:000299128000032 PM 22016501 ER PT J AU Seam, N Meduri, GU Wang, HH Nylen, ES Sun, JF Schultz, MJ Tropea, M Suffredini, AF AF Seam, Nitin Meduri, G. Umberto Wang, Honghui Nylen, Eric S. Sun, Junfeng Schultz, Marcus J. Tropea, Margaret Suffredini, Anthony F. TI Effects of methylprednisolone infusion on markers of inflammation, coagulation, and angiogenesis in early acute respiratory distress syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE ARDS; coagulation; corticosteroids; inflammation; proadrenomedullin; protein C ID ACUTE LUNG INJURY; ACTIVATED PROTEIN-C; PERSISTENT ELEVATION; CLINICAL-TRIAL; ARDS; SEPSIS; CORTICOSTEROIDS; BIOMARKERS; CYTOKINES; PULMONARY AB Objective: Evaluate the effects of methylprednisolone on markers of inflammation, coagulation, and angiogenesis during early acute respiratory distress syndrome. Design: Retrospective analysis. Setting: Four intensive care units. Subjects: Seventy-nine of 91 patients with available samples enrolled in a randomized, blinded controlled trial. Interventions: Early methylprednisolone infusion (n = 55) compared with placebo (n = 24). Measurements and Main Results: Interleukin-6, tumor necrosis factor alpha, vascular endothelial growth factor, protein C, procalcitonin, and proadrenomedullin were measured in archived plasma. Changes from baseline to day 3 and day 7 were compared between groups and in subgroups based on the precipitating cause of acute respiratory distress syndrome. Methylprednisolone therapy was associated with greater improvement in Lung Injury Score (p = .003), shorter duration of mechanical ventilation (p = .005), and lower intensive care unit mortality (p = .05) than control subjects. On days 3 and 7, methylprednisolone decreased interleukin-6 and increased protein C levels (all p < .0001) compared with control subjects. Proadrenomedullin levels were lower by day 3 with methylprednisolone treatment (p < .004). Methylprednisolone decreased interleukin-6 by days 3 and 7 in patients with pulmonary causes of acute respiratory distress syndrome but only at day 3 in those with extrapulmonary causes of acute respiratory distress syndrome. Protein C levels were increased with methylprednisolone on days 3 and 7 in patients with infectious and/or pulmonary causes of acute respiratory distress syndrome (all p < .0001) but not in patients with noninfectious or extrapulmonary causes of acute respiratory distress syndrome. Proadrenomedullin levels were decreased with methylprednisolone on day 3 in patients with infectious or extrapulmonary causes of acute respiratory distress syndrome (both p < .008) but not in noninfectious or pulmonary acute respiratory distress syndrome. Tumor necrosis factor, vascular endothelial growth factor, and procalcitonin were elevated but not differentially affected by methylprednisolone therapy. Conclusions: In early acute respiratory distress syndrome, administration of methylprednisolone was associated with improvement in important biomarkers of inflammation and coagulation and clinical outcomes. Biomarker changes varied with the precipitating cause of acute respiratory distress syndrome, suggesting that the underlying mechanisms and response to anti-inflammatory therapy may vary with the cause of acute respiratory distress syndrome. (Crit Care Med 2012; 40: 495-501) C1 [Seam, Nitin] Vet Affairs Med Ctr, Pulm Sect, Washington, DC 20422 USA. [Meduri, G. Umberto] Univ Tennessee, Hlth Sci Ctr, Div Pulm Crit Care Med, Memphis, TN USA. Memphis Vet Affairs Med Ctr, Memphis, TN USA. [Seam, Nitin; Wang, Honghui; Sun, Junfeng; Tropea, Margaret; Suffredini, Anthony F.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Nylen, Eric S.] Vet Affairs Med Ctr, Endocrinol Sect, Washington, DC 20422 USA. [Schultz, Marcus J.] Univ Amsterdam, Acad Med Ctr, Dept Intens Care Med, NL-1105 AZ Amsterdam, Netherlands. RP Seam, N (reprint author), Vet Affairs Med Ctr, Pulm Sect, 50 Irving St NW, Washington, DC 20422 USA. EM nitin.seam@va.gov RI Schultz, Marcus/K-6147-2012 FU Critical Care Medicine Department of the National Institutes of Health; National Institutes of Health FX This research was supported by the Intramural Research Program of the Critical Care Medicine Department of the National Institutes of Health.; Dr. Seam, Mr. Wang, Mr. Sun, and Dr. Suffredini received funding from the National Institutes of Health. The remaining authors have not disclosed any potential conflicts of interest. NR 37 TC 24 Z9 28 U1 0 U2 8 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 495 EP 501 DI 10.1097/CCM.0b013e318232da5e PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 879EW UT WOS:000299313500019 PM 21983371 ER PT J AU Needham, DM Davidson, J Cohen, H Hopkins, RO Weinert, C Wunsch, H Zawistowski, C Bemis-Dougherty, A Berney, SC Bienvenu, OJ Brady, SL Brodsky, MB Denehy, L Elliott, D Flatley, C Harabin, AL Jones, C Louis, D Meltzer, W Muldoon, SR Palmer, JB Perme, C Robinson, M Schmidt, DM Scruth, E Spill, GR Storey, CP Render, M Votto, J Harvey, MA AF Needham, Dale M. Davidson, Judy Cohen, Henry Hopkins, Ramona O. Weinert, Craig Wunsch, Hannah Zawistowski, Christine Bemis-Dougherty, Anita Berney, Susan C. Bienvenu, O. Joseph Brady, Susan L. Brodsky, Martin B. Denehy, Linda Elliott, Doug Flatley, Carl Harabin, Andrea L. Jones, Christina Louis, Deborah Meltzer, Wendy Muldoon, Sean R. Palmer, Jeffrey B. Perme, Christiane Robinson, Marla Schmidt, David M. Scruth, Elizabeth Spill, Gayle R. Storey, C. Porter Render, Marta Votto, John Harvey, Maurene A. TI Improving long-term outcomes after discharge from intensive care unit: Report from a stakeholders' conference SO CRITICAL CARE MEDICINE LA English DT Article DE aftercare; caregivers; continuity of patient care; critical care; follow-up studies; intensive care units; outcome assessment; patient care planning; patient care team; postintensive care syndrome; stress disorders, post-traumatic; survivors ID RESPIRATORY-DISTRESS-SYNDROME; QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; CRITICAL ILLNESS; REHABILITATION PROGRAM; FUNCTIONAL DISABILITY; COGNITIVE IMPAIRMENT; MOBILIZING PATIENTS; CRITICALLY-ILL AB Background: Millions of patients are discharged from intensive care units annually. These intensive care survivors and their families frequently report a wide range of impairments in their health status which may last for months and years after hospital discharge. Objectives: To report on a 2-day Society of Critical Care Medicine conference aimed at improving the long-term outcomes after critical illness for patients and their families. Participants: Thirty-one invited stakeholders participated in the conference. Stakeholders represented key professional organizations and groups, predominantly from North America, which are involved in the care of intensive care survivors after hospital discharge. Design: Invited experts and Society of Critical Care Medicine members presented a summary of existing data regarding the potential long-term physical, cognitive and mental health problems after intensive care and the results from studies of postintensive care unit interventions to address these problems. Stakeholders provided reactions, perspectives, concerns and strategies aimed at improving care and mitigating these long-term health problems. Measurements and Main Results: Three major themes emerged from the conference regarding: (1) raising awareness and education, (2) understanding and addressing barriers to practice, and (3) identifying research gaps and resources. Postintensive care syndrome was agreed upon as the recommended term to describe new or worsening problems in physical, cognitive, or mental health status arising after a critical illness and persisting beyond acute care hospitalization. The term could be applied to either a survivor or family member. Conclusions: Improving care for intensive care survivors and their families requires collaboration between practitioners and researchers in both the inpatient and outpatient settings. Strategies were developed to address the major themes arising from the conference to improve outcomes for survivors and families. (Crit Care Med 2012; 40: 502-509) C1 [Needham, Dale M.] Johns Hopkins Univ, OACIS Grp, Baltimore, MD 21218 USA. [Davidson, Judy] Scripps Mercy Hosp, San Diego, CA USA. [Cohen, Henry] Kingsbrook Jewish Med Ctr, Woodmere, NY USA. [Hopkins, Ramona O.] Brigham Young Univ, Intermt Med Ctr, Salt Lake City, UT USA. Brigham Young Univ, Psychol & Neurosci Ctr, Salt Lake City, UT USA. [Weinert, Craig] Univ Minnesota, Clin Outcomes Res Ctr, Minneapolis, MN USA. [Wunsch, Hannah] Columbia Univ, New York, NY USA. [Zawistowski, Christine] Mt Sinai Kravis Childrens Hosp, Brooklyn, NY USA. [Bemis-Dougherty, Anita] Amer Phys Therapy Assoc, Dept Practice, Alexandria, VA USA. [Berney, Susan C.] Austin Heath, Physiotherapy Dept, Melbourne, Vic, Australia. [Brady, Susan L.] Marianjoy Rehabil Hosp, Roselle, IL USA. [Denehy, Linda] Univ Melbourne, Melbourne Sch Hlth Sci, Melbourne, Vic, Australia. [Elliott, Doug] Univ Technol Sydney, Fac Nursing, Sydney, NSW 2007, Australia. [Flatley, Carl] Sepsis Alliance, Tampa, FL USA. [Harabin, Andrea L.] NHLBI, Div Lung Dis, Bethesda, MD 20892 USA. [Jones, Christina] Whiston Hosp, Prescot, England. [Louis, Deborah] Kaiser Sunnyside Med Ctr, Clackamus, OR USA. [Muldoon, Sean R.] Kindred Healthcare, Hosp Div, Louisville, KY USA. [Meltzer, Wendy] Illinois Citizens Better Care, Chicago, IL USA. [Perme, Christiane] Methodist Hosp, Houston, TX 77030 USA. [Robinson, Marla] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Schmidt, David M.] Kaiser Sunnyside Med Ctr, Clackamus, OR USA. [Scruth, Elizabeth] Kaiser Permanente, No Calif Qual Dept, San Jose, CA USA. [Spill, Gayle R.] Rehabil Inst Chicago, Canc Rehabil Program, Chicago, IL 60611 USA. [Storey, C. Porter] Amer Acad Hosp & Palliat Med, Boulder, CO USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Render, Marta] Vet Affairs Med Ctr, Inpatient Evaluat Ctr, Cincinnati, OH 45267 USA. [Votto, John] Hosp Special Care, New Britain, CT USA. [Harvey, Maurene A.] Soc Crit Care Med, Lake Tahoe, NV USA. RP Needham, DM (reprint author), Johns Hopkins Univ, OACIS Grp, Baltimore, MD 21218 USA. EM Dale.needham@jhmi.edu OI Denehy, Linda/0000-0002-2926-8436; Elliott, Doug/0000-0002-6081-5442 FU National Institutes of Health FX Dr. Needham has received grant support from the National Institutes of Health. Dr. Bienvenu has received funding from the National Institutes of Health. Ms. Louis is employed by Kaiser Permanente. Dr. Muldoon is employed by and has stock ownership in Kindred Healthcare. The remaining authors have not disclosed any potential conflicts of interest. NR 76 TC 238 Z9 242 U1 2 U2 34 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 502 EP 509 DI 10.1097/CCM.0b013e318232da75 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 879EW UT WOS:000299313500020 PM 21946660 ER PT J AU O'Grady, NP AF O'Grady, Naomi P. TI Zero risk for central line-associated bloodstream infections ... is this realistic? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE central venous catheters; elimination; prevention; risk ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE; INTERVENTION; OUTCOMES C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP O'Grady, NP (reprint author), NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 11 TC 5 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2012 VL 40 IS 2 BP 657 EP 658 DI 10.1097/CCM.0b013e3182372ba6 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 879EW UT WOS:000299313500042 PM 22249034 ER PT J AU Souza, ACP Yuen, PST AF Souza, Ana C. P. Yuen, Peter S. T. TI How can antibiotics worsen acute kidney injury but improve survival in experimental sepsis? SO CRITICAL CARE MEDICINE LA English DT Editorial Material ID SEPTIC SHOCK; ANTIMICROBIAL THERAPY; HYPOTENSION; INITIATION; DURATION; OUTCOMES C1 [Souza, Ana C. P.; Yuen, Peter S. T.] NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. RP Souza, ACP (reprint author), NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 FU Intramural NIH HHS [Z99 DK999999, ZIA DK043403-11] NR 15 TC 2 Z9 2 U1 0 U2 0 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 685 EP 686 DI 10.1097/CCM.0b013e318236e162 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 879EW UT WOS:000299313500061 PM 22249053 ER PT J AU Williams, M Burdsal, C Periasamy, A Lewandoski, M Sutherland, A AF Williams, Margot Burdsal, Carol Periasamy, Ammasi Lewandoski, Mark Sutherland, Ann TI Mouse primitive streak forms in situ by initiation of epithelial to mesenchymal transition without migration of a cell population SO DEVELOPMENTAL DYNAMICS LA English DT Article DE primitive streak; epithelial to mesenchymal transition; gastrulation; mouse embryo; morphogenesis ID GASTRULATING RABBIT EMBRYO; ANTERIOR VISCERAL ENDODERM; NEURAL-TUBE DEFECTS; EPIBLAST CELLS; MESODERM DIFFERENTIATION; CADHERIN EXPRESSION; AVIAN GASTRULATION; MOVEMENT PATTERNS; PROGENITOR CELLS; CLONAL ANALYSIS AB Background: During gastrulation, an embryo acquires the three primordial germ layers that will give rise to all of the tissues in the body. In amniote embryos, this process occurs via an epithelial to mesenchymal transition (EMT) of epiblast cells at the primitive streak. Although the primitive streak is vital to development, many aspects of how it forms and functions remain poorly understood. Results: Using live, 4 dimensional imaging and immunohistochemistry, we have shown that the posterior epiblast of the pre-streak murine embryo does not display convergence and extension behavior or large scale migration or rearrangement of a cell population. Instead, the primitive streak develops in situ and elongates by progressive initiation EMT in the posterior epiblast. Loss of basal lamina (BL) is the first step of this EMT, and is strictly correlated with ingression of nascent mesoderm. Once the BL is lost in a given region, cells leave the epiblast by apical constriction in order to enter the primitive streak. Conclusions: This is the first description of dynamic cell behavior during primitive streak formation in the mouse embryo, and reveals mechanisms that are quite distinct from those observed in other amniote model systems. Unlike chick and rabbit, the murine primitive streak arises in situ by progressive initiation of EMT beginning in the posterior epiblast, without large-scale movement or convergence and extension of epiblast cells. Developmental Dynamics 241:270283, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Williams, Margot; Sutherland, Ann] Univ Virginia, Dept Cell Biol, Charlottesville, VA 22908 USA. [Burdsal, Carol] Tulane Univ, Sch Sci & Engn, Dept Cell & Mol Biol, New Orleans, LA 70118 USA. [Periasamy, Ammasi] Univ Virginia, Keck Ctr Cellular Imaging, Charlottesville, VA 22908 USA. [Periasamy, Ammasi] Univ Virginia, Dept Biol, Charlottesville, VA 22908 USA. [Lewandoski, Mark] NCI, Ctr Canc Res, Frederick, MD 21701 USA. RP Sutherland, A (reprint author), Univ Virginia, Dept Cell Biol, POB 800732, Charlottesville, VA 22908 USA. EM as9n@virginia.edu OI Sutherland, Ann/0000-0003-1925-2825 FU National Science Foundation [IOS-1051294]; National Institute for Child Health and Human Development; National Institutes of Health [RO1 HD034807, T32 GM008136] FX We thank Dr. Ray Keller for critical reading of the manuscript and advice on data analysis, and the faculty and staff of the W. M. Keck Center for Cellular Imaging for advice and assistance with imaging. A. E. S. was funded by the National Science Foundation and the National Institute for Child Health and Human Development, as well as private donations from Drs. Tom and Jean Sutherland. M. W. was supported by a training grant from the National Institutes of Health.; Grant sponsor: NIH; Grant numbers: RO1 HD034807, T32 GM008136; Grant sponsor: NSF; Grant number: IOS-1051294. NR 59 TC 24 Z9 24 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD FEB PY 2012 VL 241 IS 2 BP 270 EP 283 DI 10.1002/dvdy.23711 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 880MZ UT WOS:000299412500005 PM 22170865 ER PT J AU Hasebe, T Kajita, M Fu, LZ Shi, YB Ishizuya-Oka, A AF Hasebe, Takashi Kajita, Mitsuko Fu, Liezhen Shi, Yun-Bo Ishizuya-Oka, Atsuko TI Thyroid hormone-induced sonic hedgehog signal up-regulates its own pathway in a paracrine manner in the Xenopus laevis intestine during metamorphosis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Patched (Ptc); Smoothened (Smo); Sonic hedgehog (Shh); Gli transcription factor; Xenopus laevis; metamorphosis; intestinal remodeling ID ADULT EPITHELIAL DEVELOPMENT; GASTROINTESTINAL-TRACT; EXPRESSION PROFILES; GENE-EXPRESSION; BINDING-SITE; GLI PROTEINS; FLOOR PLATE; IN-VITRO; ACTIVATION; SHH AB Background: During Xenopus laevis metamorphosis, Sonic hedgehog (Shh) is directly induced by thyroid hormone (TH) at the transcription level as one of the earliest events in intestinal remodeling. However, the regulation of other components of this signaling pathway remains to be analyzed. Here, we analyzed the spatiotemporal expression of Patched (Ptc)-1, Smoothened (Smo), Gli1, Gli2, and Gli3 during natural and TH-induced intestinal remodeling. Results: We show that all of the genes examined are transiently up-regulated in the mesenchymal tissues during intestinal metamorphosis. Conclusions: Interestingly, in the presence of protein synthesis inhibitors, Gli2 but not the others was induced by TH, suggesting that Gli2 is a direct TH response gene, while the others are likely indirect ones. Furthermore, we demonstrate by the organ culture experiment that overexpression of Shh enhances the expression of Ptc-1, Smo, and Glis even in the absence of TH, indicating that Shh regulates its own pathway components during intestinal remodeling. Developmental Dynamics 241:403414, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Hasebe, Takashi; Ishizuya-Oka, Atsuko] Nippon Med Sch, Dept Biol, Nakahara Ku, Kawasaki, Kanagawa 2110063, Japan. [Kajita, Mitsuko; Ishizuya-Oka, Atsuko] Nippon Med Sch, Dept Mol Biol, Inst Dev & Aging Sci, Nakahara Ku, Kawasaki, Kanagawa 2110063, Japan. [Fu, Liezhen; Shi, Yun-Bo] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Hasebe, T (reprint author), Nippon Med Sch, Dept Biol, Nakahara Ku, 2-297-2 Kosugi Cho, Kawasaki, Kanagawa 2110063, Japan. EM hasebet@nms.ac.jp FU JSPS [20570060]; NICHD, NIH FX We thank Drs. Masakazu Fujiwara (Nippon Medical School), Itaru Hasunuma (Toho University), Kosuke Kawamura (Waseda University) for providing us technical information; Dr. Kazuhito Takeshima (Nagoya University) for helpful discussions about Gli genes; Dr. Yoshinori Abe (Nippon Medical School) for helpful discussions about Shh signaling; and Dr. Ariel Ruiz i Altaba (University of Geneva) for kind gifts of Gli plasmids. This work was supported in part by JSPS Grants-in-Aid for Scientific Research (C) to A. I.-O., and in part by the Intramural Research Program of NICHD, NIH to Y.-B.S.; Grant sponsor: JSPS Grants-in-Aid for Scientific Research (C); Grant number: 20570060; Grant sponsor: Intramural Research Program of NICHD; NIH. NR 57 TC 7 Z9 7 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD FEB PY 2012 VL 241 IS 2 BP 403 EP 414 DI 10.1002/dvdy.23723 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 880MZ UT WOS:000299412500017 PM 22190352 ER PT J AU Lord, CC Betters, JL Ivanova, PT Milne, SB Myers, DS Madenspacher, J Thomas, G Chung, S Liu, MX Davis, MA Lee, RG Crooke, RM Graham, MJ Parks, JS Brasaemle, DL Fessler, MB Brown, HA Brown, JM AF Lord, Caleb C. Betters, Jenna L. Ivanova, Pavlina T. Milne, Stephen B. Myers, David S. Madenspacher, Jennifer Thomas, Gwynneth Chung, Soonkyu Liu, Mingxia Davis, Matthew A. Lee, Richard G. Crooke, Rosanne M. Graham, Mark J. Parks, John S. Brasaemle, Dawn L. Fessler, Michael B. Brown, H. Alex Brown, J. Mark TI CGI-58/ABHD5-Derived Signaling Lipids Regulate Systemic Inflammation and Insulin Action SO DIABETES LA English DT Article ID CHANARIN-DORFMAN-SYNDROME; IONIZATION MASS-SPECTROMETRY; DIET-INDUCED OBESITY; PHOSPHATIDIC-ACID; STORAGE DISEASE; HEPATIC STEATOSIS; CYTOPLASMIC TRIACYLGLYCEROLS; LYSOPHOSPHATIDIC ACID; HUMAN FIBROBLASTS; MESANGIAL CELLS AB Mutations of comparative gene identification 58 (CGI-58) in humans cause Chanarin-Dorfman syndrome, a rare autosomal recessive disease in which excess triacylglycerol (TAG) accumulates in multiple tissues. CGI-58 recently has been ascribed two distinct biochemical activities, including coactivation of adipose triglyceride lipase and acylation of lysophosphatidic acid (LPA). It is noteworthy that both the substrate (LPA) and the product (phosphatidic acid) of the LPA acyltransferase reaction are well-known signaling lipids. Therefore, we hypothesized that CGI-58 is involved in generating lipid mediators that regulate TAG metabolism and insulin sensitivity. Here, we show that CGI-58 is required for the generation of signaling lipids in response to inflammatory stimuli and that lipid second messengers generated by CGI-58 play a critical role in maintaining the balance between inflammation and insulin action. Furthermore, we show that CGI-58 is necessary for maximal T(H)1 cytokine signaling in the liver. This novel role for CGI-58 in cytokine signaling may explain why diminished CGI-58 expression causes severe hepatic lipid accumulation yet paradoxically improves hepatic insulin action. Collectively, these findings establish that CGI-58 provides a novel source of signaling lipids. These findings contribute insight into the basic mechanisms linking TH1 cytokine signaling to nutrient metabolism. Diabetes 61:355-363, 2012 C1 [Lord, Caleb C.; Betters, Jenna L.; Thomas, Gwynneth; Chung, Soonkyu; Liu, Mingxia; Davis, Matthew A.; Parks, John S.; Brown, J. Mark] Wake Forest Univ, Dept Pathol, Sect Lipid Sci, Sch Med, Winston Salem, NC 27109 USA. [Ivanova, Pavlina T.; Milne, Stephen B.; Myers, David S.; Brown, H. Alex] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. [Madenspacher, Jennifer; Fessler, Michael B.] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. [Lee, Richard G.; Crooke, Rosanne M.; Graham, Mark J.] ISIS Pharmaceut, Antisense Drug Discovery, Cardiovasc Grp, Carlsbad, CA 92008 USA. [Brasaemle, Dawn L.] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. RP Brown, JM (reprint author), Wake Forest Univ, Dept Pathol, Sect Lipid Sci, Sch Med, Winston Salem, NC 27109 USA. EM mabrown@wakehealth.edu RI Ivanova, Pavlina/K-8307-2012; OI Brasaemle, Dawn/0000-0002-8553-8285 FU Department of Pathology at Wake Forest University from the American Heart Association [11BGIA7840072]; National Heart, Lung, and Blood Institute [1-K99-HL-096166, 5-T32-HL-091796, 5-P01-HL-049373]; National Institute of Diabetes and Digestive and Kidney Diseases [1-F32-DK-084582, 1-R01-054797]; National Institute of General Medical Sciences LIPID MAPS [U54-GM-069338]; National Institute of Environmental Health Sciences [NIEHS Z01-ES-102005] FX This work was supported by the Department of Pathology at Wake Forest University and by grants from the American Heart Association (grant 11BGIA7840072 to J.M.B.); the National Heart, Lung, and Blood Institute (grants 1-K99-HL-096166 to J.M.B., 5-T32-HL-091796 to C.C.L., and 5-P01-HL-049373 to J.S.P.); the National Institute of Diabetes and Digestive and Kidney Diseases (grants 1-F32-DK-084582 to J.L.B. and 1-R01-054797 to D.L.B.); the National Institute of General Medical Sciences LIPID MAPS (grant U54-GM-069338 to H.A.B.); and the Intramural Research Program of the National Institute of Environmental Health Sciences (grant NIEHS Z01-ES-102005 to M.B.F.). NR 50 TC 23 Z9 23 U1 1 U2 8 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 355 EP 363 DI 10.2337/db11-0994 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 885RI UT WOS:000299798100013 PM 22228714 ER PT J AU Hiekkalinna, T Goring, HHH Lambert, B Weiss, KM Norrgrann, P Schaffer, AA Terwilliger, JD AF Hiekkalinna, Tero Goering, Harald H. H. Lambert, Brian Weiss, Kenneth M. Norrgrann, Petri Schaeffer, Alejandro A. Terwilliger, Joseph D. TI On the statistical properties of family-based association tests in datasets containing both pedigrees and unrelated case-control samples SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE power; type-I error; genetic linkage analysis; linkage disequilibrium; family-based association; genome-wide association studies ID LINKAGE DISEQUILIBRIUM ANALYSIS; GENOME-WIDE SEARCH; SUSCEPTIBILITY LOCUS; NUCLEAR FAMILIES; GENETIC-ANALYSIS; UNIFIED APPROACH; POPULATION; ASSIGNMENT; DISEASE; IDENTIFICATION AB A common approach to genetic mapping of loci for complex diseases is to perform a genome-wide association study (GWAS) by analyzing a vast number of SNP markers in cohorts of unrelated cases and controls. A direct motivation for the case-control design is that unrelated, affected individuals can be easier to collect than large families with multiple affected persons in the Western world. Despite its higher potential power, investigators have not actively pursued family ascertainment in part because of a dearth of methods for analyzing such correlated data on a large scale. We examine the statistical properties of several commonly used family-based association tests, as to their performance using real-life mixtures of families and singletons taken from our own migraine and schizophrenia studies, as well as population-based data for a complex trait simulated with the evolutionary phenogenetic simulator, ForSim. In virtually every situation, the full likelihood-based methods in the PSEUDOMARKER program outperformed those implemented in FBAT, GENEHUNTER TDT, PLINK (family-based options), HRR/HHRR, QTDT, TRANSMIT, UNPHASED, MENDEL, and LAMP. We further show that GWAS is much more powerful when family samples are used rather than unrelateds, on a genotype-by-genotype basis. European Journal of Human Genetics (2012) 20, 217-223; doi:10.1038/ejhg.2011.173; published online 21 September 2011 C1 [Hiekkalinna, Tero; Norrgrann, Petri; Terwilliger, Joseph D.] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland. [Goering, Harald H. H.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Lambert, Brian; Weiss, Kenneth M.] Penn State Univ, Dept Anthropol, State Coll, PA USA. [Schaeffer, Alejandro A.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, US Dept HHS, Bethesda, MD 20892 USA. [Terwilliger, Joseph D.] Columbia Univ, Dept Psychiat, New York, NY USA. [Terwilliger, Joseph D.] Columbia Univ, Dept Genet & Dev, New York, NY USA. [Terwilliger, Joseph D.] Columbia Univ, Columbia Genome Ctr, New York, NY USA. [Terwilliger, Joseph D.] New York State Psychiat Inst & Hosp, Div Med Genet, New York, NY 10032 USA. [Hiekkalinna, Tero; Norrgrann, Petri; Terwilliger, Joseph D.] Natl Inst Hlth & Welf, Unit Publ Hlth Genom, Helsinki, Finland. RP Hiekkalinna, T (reprint author), Biomedicum Helsinki, Publ Hlth Genom Unit, Natl Inst Hlth & Welf THL, POB 104, FIN-00251 Helsinki, Finland. EM tero.hiekkalinna@helsinki.fi RI Schaffer, Alejandro/F-2902-2012 FU Academy of Finland from the National Institutes of Health [MH84995, MH59490, RR017515]; Helsingin Sanomat Centennial Foundation; Biomedicum Helsinki Foundation; Emil Aaltonen Foundation; Otto A. Malm Foundation; Jenny and Antti Wihuri Foundation; Finnish Cultural Society; SBC Foundation; NIH, NLM FX This research work was funded by the FiDiPro program of the Academy of Finland, Grants MH84995, MH59490 and RR017515 from the National Institutes of Health, the Helsingin Sanomat Centennial Foundation, Biomedicum Helsinki Foundation, Emil Aaltonen Foundation, Otto A. Malm Foundation, Jenny and Antti Wihuri Foundation, Finnish Cultural Society, and the SBC Foundation are gratefully acknowledged. This research was supported in part by the Intramural Research Program of the NIH, NLM (AAS). Maija Wessman, Verneri Anttila, Mari Kaunisto, and Tiina Paunio are acknowledged for providing Finnish migraine and schizophrenia pedigree structures for simulation studies. Markus Perola and Leena Peltonen-Palotie are greatly acknowledged for their guidance and support over the years. The great majority of simulations were executed on the Linux-based supercomputers of the Finnish IT Center for Science (CSC). CSC is greatly acknowledged. Thanks to three reviewers for numerous helpful suggestions to improve the manuscript. NR 52 TC 6 Z9 7 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD FEB PY 2012 VL 20 IS 2 BP 217 EP 223 DI 10.1038/ejhg.2011.173 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 879IN UT WOS:000299323000023 PM 21934707 ER PT J AU Greub, G Gikas, A Heinzen, RA Dumler, JS AF Greub, Gilbert Gikas, Achilles Heinzen, Robert A. Dumler, J. Stephen TI Rickettsia and other intracellular bacteria: recent outbreaks, novel pathogens, emerging diseases, new tools, and outstanding discoveries SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Editorial Material C1 [Greub, Gilbert] Univ Lausanne, Inst Microbiol, CH-1011 Lausanne, Switzerland. [Gikas, Achilles] Univ Hosp Heraklion, Dept Internal Med & Infect Dis, Iraklion, NE, Greece. [Heinzen, Robert A.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Dumler, J. Stephen] Johns Hopkins Univ, Sch Med, Div Med Microbiol, Dept Pathol, Baltimore, MD 21205 USA. RP Greub, G (reprint author), Univ Lausanne, Inst Microbiol, Rue Bugnon 48, CH-1011 Lausanne, Switzerland. EM gilbert.greub@chuv.ch; gikas@med.uoc.gr; rheinzen@niaid.nih.gov; sdumler@jhmi.edu OI Gikas, Achilleas/0000-0002-8455-9631 NR 3 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD FEB PY 2012 VL 64 IS 1 SI SI BP 1 EP 2 DI 10.1111/j.1574-695X.2011.00915.x PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 874LA UT WOS:000298957500001 PM 22118608 ER PT J AU Chaves, LF Morrison, AC Kitron, UD Scott, TW AF Chaves, Luis F. Morrison, Amy C. Kitron, Uriel D. Scott, Thomas W. TI Nonlinear impacts of climatic variability on the density-dependent regulation of an insect vector of disease SO GLOBAL CHANGE BIOLOGY LA English DT Article DE Aedes aegypti; climate change; exogenous forcing; kurtosis; modeling; mosquito; population regulation; Schmalhausen's law ID AEDES-AEGYPTI DIPTERA; ECOLOGICAL TIME-SERIES; YELLOW-FEVER MOSQUITO; POPULATION-DYNAMICS; INTRASPECIFIC COMPETITION; MALARIA; CULICIDAE; PATTERNS; TEMPERATURE; EVOLUTION AB Aedes aegypti is one of the most common urban tropical mosquito species and an important vector of dengue, chikungunya, and yellow fever viruses. It is also an organism with a complex life history where larval stages are aquatic and adults are terrestrial. This ontogenetic niche shift could shape the density-dependent regulation of this and other mosquito species, because events that occur during the larval stages impact adult densities. Herein, we present results from simple density-dependent mathematical models fitted using maximum likelihood methods to weekly time series data from Puerto Rico and Thailand. Density-dependent regulation was strong in both populations. Analysis of climatic forcing indicated that populations were more sensitive to climatic variables with low kurtosis, i.e., climatic factors highly variable around the median, rainfall in Puerto Rico, and temperature in Thailand. Changes in environmental variability appear to drive sharp changes in the abundance of mosquitoes. The identification of density-independent (i.e., exogenous) variables forcing sharp changes in disease vector populations using the exogenous factors statistical properties, such as kurtosis, could be useful to assess the impacts of changing climate patterns on the transmission of vector-borne diseases. C1 [Chaves, Luis F.] Hokkaido Univ, Grad Sch Environm Sci, Sapporo, Hokkaido 0600810, Japan. [Chaves, Luis F.] Hokkaido Univ, Excellence Program Integrated Field Environm Sci, Global Ctr, Sapporo, Hokkaido 0600810, Japan. [Chaves, Luis F.] Univ Nacl, Programa Invest Enfermedades Trop, Escuela Med Vet, Heredia, Costa Rica. [Morrison, Amy C.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Kitron, Uriel D.] Emory Univ, Dept Environm Studies, Atlanta, GA 30322 USA. [Kitron, Uriel D.; Scott, Thomas W.] Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. RP Chaves, LF (reprint author), Hokkaido Univ, Grad Sch Environm Sci, Sapporo, Hokkaido 0600810, Japan. EM lchaves@ees.hokudai.ac.jp RI Chaves, Luis Fernando/F-3448-2010 OI Chaves, Luis Fernando/0000-0002-5301-2764 FU American Society of Tropical Medicine and Hygiene (ASTMH); Japan Society for the Promotion of Science (JSPS); Emory University; Research and Policy for Infectious Disease Dynamics (RAPIDD) of the Science and Technology Directorate; Fogarty International Center, National Institutes of Health FX Valuable comments were provided by Prof Chepina Hernandez, Prof N. Minakawa, Prof T. Takada, Dr A. Ponlawat, and Dr T. Revilla. LFC was supported by a Gorgas Memorial Research Award from the American Society of Tropical Medicine and Hygiene (ASTMH), and by a Grant in Aid for Research of Japan Society for the Promotion of Science (JSPS). UDK was supported by Emory University. UDK and TWS were supported by Research and Policy for Infectious Disease Dynamics (RAPIDD) mosquito-borne disease program of the Science and Technology Directorate and the Fogarty International Center, National Institutes of Health. NR 62 TC 34 Z9 35 U1 4 U2 56 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1354-1013 J9 GLOBAL CHANGE BIOL JI Glob. Change Biol. PD FEB PY 2012 VL 18 IS 2 BP 457 EP 468 DI 10.1111/j.1365-2486.2011.02522.x PG 12 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 875PB UT WOS:000299042500006 ER PT J AU Maltsev, VA Lakatta, EG AF Maltsev, Victor A. Lakatta, Edward G. TI The funny current in the context of the coupled-clock pacemaker cell system SO HEART RHYTHM LA English DT Editorial Material DE Intracellular Ca2+; Cardiac pacemaker cells ID PIG SINOATRIAL NODE; CA2+ RELEASES C1 [Maltsev, Victor A.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, IRP, NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, IRP, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000863-02] NR 13 TC 19 Z9 19 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD FEB PY 2012 VL 9 IS 2 BP 302 EP 307 DI 10.1016/j.hrthm.2011.09.022 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 882DL UT WOS:000299541600033 PM 21925132 ER PT J AU Mirabello, L Yeager, M Chowdhury, S Qi, L Deng, X Wang, Z Hutchinson, A Savage, SA AF Mirabello, L. Yeager, M. Chowdhury, S. Qi, L. Deng, X. Wang, Z. Hutchinson, A. Savage, S. A. TI Worldwide genetic structure in 37 genes important in telomere biology SO HEREDITY LA English DT Article DE telomere; selection; single-nucleotide polymorphism; HGDP; HapMap ID MULTILOCUS GENOTYPE DATA; GENOME-WIDE ASSOCIATION; BASAL-CELL CARCINOMA; HUMAN-POPULATIONS; NATURAL-SELECTION; LINKAGE DISEQUILIBRIUM; SUSCEPTIBILITY LOCI; STATISTICAL-METHOD; COMMON VARIANTS; HAPLOTYPE MAP AB Telomeres form the ends of eukaryotic chromosomes and are vital in maintaining genetic integrity. Telomere dysfunction is associated with cancer and several chronic diseases. Patterns of genetic variation across individuals can provide keys to further understanding the evolutionary history of genes. We investigated patterns of differentiation and population structure of 37 telomere maintenance genes among 53 worldwide populations. Data from 898 unrelated individuals were obtained from the genome-wide scan of the Human Genome Diversity Panel (HGDP) and from 270 unrelated individuals from the International HapMap Project at 716 single-nucleotide polymorphism (SNP) loci. We additionally compared this gene set to HGDP data at 1396 SNPs in 174 innate immunity genes. The majority of the telomere biology genes had low to moderate haplotype diversity (45-85%), high ancestral allele frequencies (> 60%) and low differentiation (F(ST) <0.10). Heterozygosity and differentiation were significantly lower in telomere biology genes compared with the innate immunity genes. There was evidence of evolutionary selection in ACD, TERF21P, NOLA2, POT1 and TNKS in this data set, which was consistent in HapMap 3. TERT had higher than expected levels of haplotype diversity, likely attributable to a lack of linkage disequilibrium, and a potential cancer-associated SNP in this gene, rs2736100, varied substantially in genotype frequency across major continental regions. It is possible that the genes under selection could influence telomere biology diseases. As a group, there appears to be less diversity and differentiation in telomere biology genes than in genes with different functions, possibly due to their critical role in telomere maintenance and chromosomal stability. Heredity (2012) 108, 124-133; doi:10.1038/hdy.2011.55; published online 6 July 2011 C1 [Mirabello, L.; Savage, S. A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Yeager, M.; Chowdhury, S.; Qi, L.; Deng, X.; Wang, Z.; Hutchinson, A.] NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, NIH 6120 Execut Blvd,EPS-7018, Bethesda, MD 20892 USA. EM savagesh@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, and with federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The cc:intent of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. We thank the staff of the NCI core genotyping facility, Dr Stephen Chanock, NCI and Elliott Richards, NCI, for valuable assistance and helpful discussions. NR 71 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0018-067X J9 HEREDITY JI Heredity PD FEB PY 2012 VL 108 IS 2 BP 124 EP 133 DI 10.1038/hdy.2011.55 PG 10 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 882UR UT WOS:000299589900005 PM 21731055 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 Pineda-Alvarez, DE Roessler, E Hu, P Srivastava, K Solomon, BD Siple, CE Fan, CM Muenke, M AF Pineda-Alvarez, Daniel E. Roessler, Erich Hu, Ping Srivastava, Kshitij Solomon, Benjamin D. Siple, C. Evan Fan, Chen-Ming Muenke, Maximilian TI Missense substitutions in the GAS1 protein present in holoprosencephaly patients reduce the affinity for its ligand, SHH SO HUMAN GENETICS LA English DT Article ID SONIC-HEDGEHOG GENE; LOSS-OF-FUNCTION; HUMAN SIX3 GENE; EMBRYONIC-DEVELOPMENT; MUTATIONS; PHENOTYPE; SPECTRUM; DISEASE; BINDING; ZIC2 AB Holprosencephaly (HPE) is the most common disorder of the developing forebrain in humans, and is characterized by varying degrees of abnormal union of the cerebral hemispheres. These defects are typically co-associated with midline craniofacial anomalies. The combination of forebrain and craniofacial defects that comprise HPE can present along a broad and variable phenotypic spectrum. Both the SHH and NODAL signaling pathways play important roles in the pathogenesis of this disorder. Disruption of these pathways by chromosomal rearrangements, mutations in pathway-related genes and/or biochemical alterations are proposed to contribute to HPE in a large number of patients. Additional factors that are not yet fully delineated are also very likely to be involved in the pathogenesis and phenotypic heterogeneity of the disorder. Genetic loss of GAS1, a cell membrane receptor and positive regulator of SHH, has been demonstrated to contribute to the HPE phenotypic spectrum in animal models. We have evaluated the coding and flanking sequence of GAS1 in 394 patients who have clinical findings within the HPE phenotypic spectrum, and now report five novel missense sequence variants among five unrelated HPE probands. Finally, we tested the effect of these variants (as well as previously reported GAS1 variants) on the ability of GAS1 to bind to SHH. Here, we demonstrate that sequence variants in GAS1 can impair its physical interaction with SHH, suggesting a decrease in the SHH downstream signaling cascade as a pathogenic mechanism of disease. C1 [Pineda-Alvarez, Daniel E.; Roessler, Erich; Hu, Ping; Srivastava, Kshitij; Solomon, Benjamin D.; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Siple, C. Evan; Fan, Chen-Ming] Carnegie Inst Sci, Dept Embryol, Baltimore, MD 21218 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,Bldg 35,Room 1B403, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov FU Division of Intramural Research (DIR) of the National Human Genome Research Institute [RO1 DK084963] FX We thank the families who participated in these research studies, and the National Institute of Neurological Disorders and Stroke's (NINDS) DNA Sequencing Facility for their technical support with DNA sequencing. This work was supported in part by the Division of Intramural Research (DIR) of the National Human Genome Research Institute (MM) and RO1 DK084963 (C-M F). NR 40 TC 23 Z9 23 U1 0 U2 2 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 301 EP 310 DI 10.1007/s00439-011-1078-6 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 876QQ UT WOS:000299123000012 PM 21842183 ER PT J AU Raza, MH Amjad, R Riazuddin, S Drayna, D AF Raza, Muhammad Hashim Amjad, Rana Riazuddin, Sheikh Drayna, Dennis TI Studies in a consanguineous family reveal a novel locus for stuttering on chromosome 16q SO HUMAN GENETICS LA English DT Article ID LINKAGE ANALYSIS C1 [Raza, Muhammad Hashim; Drayna, Dennis] Natl Inst Deafness & Other Commun Disorders NIDCD, NIH, Bethesda, MD USA. [Amjad, Rana; Riazuddin, Sheikh] Univ Punjab, Allama Iqbal Med Res Ctr, Lahore, Pakistan. [Amjad, Rana; Riazuddin, Sheikh] Univ Punjab, Ctr Excellence Mol Biol, Lahore, Pakistan. RP Drayna, D (reprint author), Natl Inst Deafness & Other Commun Disorders NIDCD, NIH, Bethesda, MD USA. EM drayna@nidcd.nih.gov FU Higher Education Commission; Ministry of Science and Technology, Islamabad, Pakistan; National Institute on Deafness and Other Communication Disorders/National Institutes of Health [Z01-000046-11] FX We thank Ms. Bushra Raza for assistance with stuttering diagnosis, and A. Schaffer, T. Friedman, and R. Morell for helpful comments on the manuscript. We particularly thank the family members who participated in this research study. This work was supported by the Higher Education Commission and the Ministry of Science and Technology, Islamabad, Pakistan and by the National Institute on Deafness and Other Communication Disorders/National Institutes of Health Intramural Grant # Z01-000046-11. NR 6 TC 8 Z9 9 U1 0 U2 2 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 311 EP 313 DI 10.1007/s00439-011-1134-2 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 876QQ UT WOS:000299123000013 PM 22205390 ER PT J AU Bornstein, MH Mash, C Arterberry, ME Manian, N AF Bornstein, Marc H. Mash, Clay Arterberry, Martha E. Manian, Nanmathi TI Object perception in 5-month-old infants of clinically depressed and nondepressed mothers SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE Object perception; Maternal depression ID POSTNATAL DEPRESSION; MATERNAL DEPRESSION; POSTPARTUM DEPRESSION; COGNITIVE-DEVELOPMENT; ORIENTATION DISCRIMINATION; FAMILIARIZATION TIME; PARENTING BEHAVIOR; CHILDREN; IMPACT; PREFERENCES AB Five-month-old infants of clinically depressed and nondepressed mothers were familiarized to a wholly novel object and afterward tested for their discrimination of the same object presented in the familiar and in a novel perspective. Infants in both groups were adequately familiarized, but infants of clinically depressed mothers failed to discriminate between novel and familiar views of the object, whereas infants of nondepressed mothers successfully discriminated. The difference in discrimination between infants of depressed and nondepressed mothers is discussed in light of infants' differential object processing and maternal sociodemographics, mind-mindedness, depression, stress, and interaction styles that may moderate opportunities for infants to learn about their world or influence the development of their perceptuocognitive capacities. Published by Elsevier Inc. C1 [Bornstein, Marc H.; Mash, Clay] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Arterberry, Martha E.] Colby Coll, Waterville, ME 04901 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov FU Intramural NIH HHS [Z01 HD001119-20] NR 63 TC 1 Z9 1 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD FEB PY 2012 VL 35 IS 1 BP 150 EP 157 DI 10.1016/j.infbeh.2011.07.008 PG 8 WC Psychology, Developmental SC Psychology GA 881NE UT WOS:000299492600014 PM 21903275 ER PT J AU Burstein, M Georgiades, K Lamers, F Swanson, SA Cui, LH He, JP Avenevoli, S Merikangas, KR AF Burstein, Marcy Georgiades, Katholiki Lamers, Femke Swanson, Sonja A. Cui, Lihong He, Jian-Ping Avenevoli, Shelli Merikangas, Kathleen R. TI Empirically Derived Subtypes of Lifetime Anxiety Disorders: Developmental and Clinical Correlates in US Adolescents SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE anxiety disorders; lifetime comorbidity; epidemiology; adolescents; National Coinorbidity Survey Replication-Adolescent Supplement (NCS-A) ID COMORBIDITY SURVEY REPLICATION; LATENT CLASS ANALYSIS; SUPPLEMENT NCS-A; BEHAVIORAL GROUP-THERAPY; COMMON MENTAL-DISORDERS; DSM-IV ANXIETY; SOCIAL PHOBIA; YOUNG-ADULTS; CHILD PSYCHOPATHOLOGY; DEPRESSIVE SYMPTOMS AB Objective: The current study examined the sex- and age-specific structure and comorbidity of lifetime anxiety disorders among U.S. adolescents. Method: The sample consisted of 2,539 adolescents (1,505 females and 1,034 males) from the National Comorbidity Survey Adolescent Supplement who met criteria for Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev. [DSM-IV-TR]) lifetime anxiety disorders (American Psychiatric Association, 2000). Adolescents ranged in age from 13 to 18 years (M = 15.2 years, SE = 0.08 years) and were 39% non-White. Multiple-group latent class analysis was conducted by adolescent sex and age to identify subgroups of adolescents with similar anxiety disorder profiles. Developmental and clinical correlates of empirically derived classes were also examined to assess the nomological validity of identified subgroups. Results: A 7-class solution provided the best tit to the data, with classes defined primarily by one rather than multiple anxiety disorders. Results also indicated that classes displayed similar diagnostic profiles across age, but varied by sex. Classes characterized by multiple anxiety disorders were consistently associated with a greater degree of persistence, clinical severity, impairment, and comorbidity with other DSM-IV-TR psychiatric disorders. Conclusions: The presentation of lifetime anxiety disorders among adolescents and the observation of unique correlates of specific classes provide initial evidence for the utility of individual DSM-IV-TR anxiety disorder categories. Although findings of the present study should be considered preliminary, results emphasize the potential value of early intervention and gender-specific conceptualization and treatment of anxiety disorders. C1 [Burstein, Marcy; Lamers, Femke; Cui, Lihong; He, Jian-Ping; Merikangas, Kathleen R.] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA. [Georgiades, Katholiki] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. [Swanson, Sonja A.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Cambridge, MA 02138 USA. [Avenevoli, Shelli] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA. RP Burstein, M (reprint author), NIMH, Genet Epidemiol Res Branch, Bldg 35,Room 1A104,35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM marcy.burstein@nih.gov RI Lamers, Femke/G-5161-2012 FU Intramural NIH HHS; NIDA NIH HHS [R01 DA016558, R01 DA016558-01]; NIMH NIH HHS [U01 MH060220, U01 MH060220-01, U01-MH60220] NR 92 TC 11 Z9 11 U1 3 U2 11 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD FEB PY 2012 VL 80 IS 1 BP 102 EP 115 DI 10.1037/a0026069 PG 14 WC Psychology, Clinical SC Psychology GA 882SX UT WOS:000299585300010 PM 22081863 ER PT J AU Hsu, JC Di Pasquale, G Harunaga, JS Onodera, T Hoffman, MP Chiorini, JA Yamada, KM AF Hsu, J. C. Di Pasquale, G. Harunaga, J. S. Onodera, T. Hoffman, M. P. Chiorini, J. A. Yamada, K. M. TI Viral Gene Transfer to Developing Mouse Salivary Glands SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE AAV; embryonic; gene transfer; organogenesis; salivary glands; transduction ID VIRUS TYPE-2 INFECTION; GROWTH-FACTOR RECEPTOR; BRANCHING MORPHOGENESIS; SUBMANDIBULAR-GLAND; SYSTEMS-ANALYSIS; EXPRESSION; CELL; CORECEPTOR; DYNAMICS; DNA AB Branching morphogenesis is essential for the formation of salivary glands, kidneys, lungs, and many other organs during development, but the mechanisms underlying this process are not adequately understood. Microarray and other gene expression methods have been powerful approaches for identifying candidate genes that potentially regulate branching morphogenesis. However, functional validation of the proposed roles for these genes has been severely hampered by the absence of efficient techniques to genetically manipulate cells within embryonic organs. Using ex vivo cultured embryonic mouse submandibular glands (SMGs) as models to study branching morphogenesis, we have identified new vectors for viral gene transfer with high efficiency and cell-type specificity to developing SMGs. We screened adenovirus, lentivirus, and 11 types of adeno-associated viruses (AAV) for their ability to transduce embryonic day 12 or 13 SMGs. We identified two AAV types, AAV2 and bovine AAV (BAAV), that are selective in targeting expression differentially to SMG epithelial and mesenchymal cell populations, respectively. Transduction of SMG epithelia with self-complementary (sc) AAV2 expressing fibroblast growth factor 7 (Fgf7) supported gland survival and enhanced SMG branching morphogenesis. Our findings represent, to our knowledge, the first successful selective gene targeting to epithelial vs. mesenchymal cells in an organ undergoing branching morphogenesis. C1 [Hsu, J. C.; Harunaga, J. S.; Onodera, T.; Hoffman, M. P.; Yamada, K. M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Di Pasquale, G.; Chiorini, J. A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bldg 30,Room 426,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM kenneth.yamada@nih.gov RI Onodera, Tomohiro/G-1686-2012; OI Yamada, Kenneth/0000-0003-1512-6805 FU Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institutes of Health [ZIA DE000525] FX The authors thank Shelagh Johnson for excellent editing. This work was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institutes of Health, Grant no. ZIA DE000525. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 30 TC 4 Z9 4 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 2012 VL 91 IS 2 BP 197 EP 202 DI 10.1177/0022034511429346 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 878QT UT WOS:000299272300015 PM 22095070 ER PT J AU Bachmann-Gagescu, R Ishak, GE Dempsey, JC Adkins, J O'Day, D Phelps, IG Gunay-Aygun, M Kline, AD Szczaluba, K Martorell, L Alswaid, A Alrasheed, S Pai, S Izatt, L Ronan, A Parisi, MA Mefford, H Glass, I Doherty, D AF Bachmann-Gagescu, Ruxandra Ishak, Gisele E. Dempsey, Jennifer C. Adkins, Jonathan O'Day, Diana Phelps, Ian G. Gunay-Aygun, Meral Kline, Antonie D. Szczaluba, Krzysztof Martorell, Loreto Alswaid, Abdulrahman Alrasheed, Shatha Pai, Shashidhar Izatt, Louise Ronan, Anne Parisi, Melissa A. Mefford, Heather Glass, Ian Doherty, Dan TI Genotype-phenotype correlation in CC2D2A-related Joubert syndrome reveals an association with ventriculomegaly and seizures SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID BARDET-BIEDL-SYNDROME; MECKEL-GRUBER-SYNDROME; OUTER SEGMENT DEVELOPMENT; RETINAL DEGENERATION; VESICLE TRAFFICKING; SYNDROME GENE; MUTATIONS; PROTEIN; CC2D2A; CILIOPATHIES AB Background Joubert syndrome (JS) is a ciliopathy characterised by a distinctive brain malformation (the 'molar tooth sign'), developmental delay, abnormal eye movements and abnormal breathing pattern. Retinal dystrophy, cystic kidney disease, liver fibrosis and polydactyly are variably present, resulting in significant phenotypic heterogeneity and overlap with other ciliopathies. JS is also genetically heterogeneous, resulting from mutations in 13 genes. These factors render clinical/molecular diagnosis and management challenging. CC2D2A mutations are a relatively common cause of JS and also cause Meckel syndrome. The clinical consequences of CC2D2A mutations in patients with JS have been incompletely reported. Methods Subjects with JS from 209 families were evaluated to identify mutations in CC2D2A. Clinical and imaging features in subjects with CC2D2A mutations were compared with those in subjects without CC2D2A mutations and reports in the literature. Results 10 novel CC2D2A mutations in 20 subjects were identified; a summary is provided of all published CC2D2A mutations. Subjects with CC2D2A-related JS were more likely to have ventriculomegaly (p<0.0001) and seizures (p=0.024) than subjects without CC2D2A mutations. No mutation-specific genotype-phenotype correlations could be identified, but the findings confirm the observation that mutations that cause CC2D2A-related JS are predicted to be less deleterious than mutations that cause CC2D2A-related Meckel syndrome. Missense variants in the coiled-coil and C2 domains, as well as the C-terminal region, identify these regions as important for the biological mechanisms underlying JS. Conclusions CC2D2A testing should be prioritised in patients with JS and ventriculomegaly and/or seizures. Patients with CC2D2A-related JS should be monitored for hydrocephalus and seizures. C1 [Bachmann-Gagescu, Ruxandra; Dempsey, Jennifer C.; Adkins, Jonathan; O'Day, Diana; Phelps, Ian G.; Mefford, Heather; Glass, Ian; Doherty, Dan] Univ Washington, Div Med Genet, Dept Pediat, Seattle, WA 98195 USA. [Ishak, Gisele E.] Univ Washington, Dept Radiol, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Gunay-Aygun, Meral] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Kline, Antonie D.] Greater Baltimore Med Ctr, Harvey Inst Human Genet, Baltimore, MD USA. [Szczaluba, Krzysztof] Inst Mother & Child Hlth, Dept Med Genet, Warsaw, Poland. [Martorell, Loreto] Hosp St Joan de Deu, Mol Genet Sect, Barcelona, Spain. [Alswaid, Abdulrahman; Alrasheed, Shatha] King Abdul Aziz Med City, Dept Pediat, Riyadh, Saudi Arabia. [Pai, Shashidhar] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Izatt, Louise] Guys & St Thomas NHS Fdn Trust, Dept Clin Genet, London, England. [Ronan, Anne] Hunter Genet Unit, Waratah, NSW, Australia. [Parisi, Melissa A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Doherty, Dan] Univ Washington, Div Dev Med, Dept Pediat, Seattle, WA 98195 USA. RP Doherty, D (reprint author), Univ Washington, Div Med Genet, Dept Pediat, Box 356320,RR-249,1959 NE Pacific St, Seattle, WA 98195 USA. EM ddoher@uw.edu RI Bachmann-Gagescu, Ruxandra/A-8444-2016 OI Bachmann-Gagescu, Ruxandra/0000-0002-3571-5271 FU National Institute of Health [5KL2RR025015, R01NS064077, K12HD043376]; March of Dimes Foundation [5-FY09-13]; Arc of Washington Trust; Lung GO Sequencing Project [HL-102923]; WHI [HL-102924]; Broad GO Sequencing Project [HL-102925]; Seattle GO Sequencing Project [HL-102926]; Heart GO Sequencing Project [HL-103010] FX This work was supported by National Institute of Health grants 5KL2RR025015 and R01NS064077 to DD, and K12HD043376 to RB-G, by Basil O'Connor Start Scholar Research Grant No 5-FY09-13 from the March of Dimes Foundation to DD, and by an Arc of Washington Trust Fund grant to DD. We would also like to thank the NHLBI GO Exome Sequencing Project and its ongoing studies which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926) and the Heart GO Sequencing Project (HL-103010). NR 48 TC 17 Z9 18 U1 3 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD FEB PY 2012 VL 49 IS 2 BP 126 EP 137 DI 10.1136/jmedgenet-2011-100552 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 879DC UT WOS:000299308900010 PM 22241855 ER PT J AU Warren, KE Gururangan, S Geyer, JR McLendon, RE Poussaint, TY Wallace, D Balis, FM Berg, SL Packer, RJ Goldman, S Minturn, JE Pollack, IF Boyett, JM Kun, LE AF Warren, Katherine E. Gururangan, Sri Geyer, J. Russell McLendon, Roger E. Poussaint, Tina Young Wallace, Dana Balis, Frank M. Berg, Stacey L. Packer, Roger J. Goldman, Stewart Minturn, Jane E. Pollack, Ian F. Boyett, James M. Kun, Larry E. TI A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioma; Pediatric; Resistance; Alkylating agent; Brainstem glioma; AGT; MGMT ID NERVOUS-SYSTEM TUMORS; MGMT PROMOTER METHYLATION; CHILDRENS ONCOLOGY GROUP; MALIGNANT GLIOMA; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ANTITUMOR IMIDAZOTETRAZINES; GLIOBLASTOMA-MULTIFORME; PLUS O-6-BENZYLGUANINE; DRUG TEMOZOLOMIDE; MISMATCH REPAIR AB To estimate the sustained (a parts per thousand yen8 weeks) objective response rate in pediatric patients with recurrent or progressive high-grade gliomas (HGG, Stratum A) or brainstem gliomas (BSG, Stratum B) treated with the combination of O6-benzylguanine (O6BG) and temozolomide(A (R)) (TMZ). Patients received O6BG 120 mg/m(2)/d IV followed by TMZ 75 mg/m(2)/d orally daily for 5 consecutive days of each 28-day course. The target objective response rate to consider the combination active was 17%. A two-stage design was employed. Forty-three patients were enrolled; 41 were evaluable for response, including 25 patients with HGG and 16 patients with BSG. The combination of O6BG and TMZ was tolerable, and the primary toxicities were myelosuppression and gastrointestinal symptoms. One sustained (a parts per thousand yen8 weeks) partial response was observed in the HGG cohort; no sustained objective responses were observed in the BSG cohort. Long-term (a parts per thousand yen6 courses) stable disease (SD) was observed in 4 patients in Stratum A and 1 patient in Stratum B. Of the 5 patients with objective response or long-term SD, 3 underwent central review with 2 reclassified as low-grade gliomas. The combination of O6BG and TMZ did not achieve the target response rate for activity in pediatric patients with recurrent or progressive HGG and BSG. C1 [Warren, Katherine E.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Gururangan, Sri; McLendon, Roger E.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Geyer, J. Russell] Seattle Childrens Hosp, Seattle, WA USA. [Poussaint, Tina Young] Childrens Hosp, Boston, MA 02115 USA. [Wallace, Dana; Boyett, James M.] Operat & Biostat Ctr Pediat Brain Tumor Consortiu, Memphis, TN USA. [Balis, Frank M.; Minturn, Jane E.] Childrens Hosp, Philadelphia, PA 19104 USA. [Berg, Stacey L.] Texas Childrens Canc Ctr, Houston, TX USA. [Packer, Roger J.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Goldman, Stewart] Childrens Mem Hosp, Chicago, IL 60614 USA. [Pollack, Ian F.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Kun, Larry E.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Warren, KE (reprint author), NCI, Pediat Oncol Branch, Bldg 10 CRC,Room 1-5750, Bethesda, MD 20892 USA. EM warrenk@mail.nih.gov FU NIH [U01 CA81457, 5M01RR000188]; American Lebanese Syrian Associated Charities FX This work was supported in part by NIH grant U01 CA81457 for the Pediatric Brain Tumor Consortium, NIH grant 5M01RR000188, and the American Lebanese Syrian Associated Charities, and the intramural program of the NIH. The authors and the PBTC acknowledge the protocol management of Mr. Christopher Smith, the central pathology review participation of Dr. Adesina Adekunle and Dr. Veena Rajaram and the statistical support of Mr. Shawn Lesh. NR 38 TC 15 Z9 16 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD FEB PY 2012 VL 106 IS 3 BP 643 EP 649 DI 10.1007/s11060-011-0709-z PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 879LX UT WOS:000299331800022 PM 21968943 ER PT J AU Emaminia, A Corcoran, PC Siegenthaler, MP Means, M Rasmussen, S Krause, L LaPar, DJ Horvath, KA AF Emaminia, Abbas Corcoran, Phillip C. Siegenthaler, Michael P. Means, Melissa Rasmussen, Sarah Krause, Linda LaPar, Damien J. Horvath, Keith A. TI The universal bed model for patient care improves outcome and lowers cost in cardiac surgery SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Western-Thoracic-Surgical-Association CY JUN 22-25, 2011 CL Colorado Springs, CO SP Western Thorac Surg Assoc ID ROOMS AB Objective: With the escalating demands to increase the efficiency and decrease the cost, innovations in postoperative cardiac surgical patient care are needed. The universal bed model is an innovative care delivery system that allows patient care to be managed in one setting from postoperation to discharge. We hypothesized that the universal bed model in the context of cardiac surgery would improve outcomes and efficacy. Methods: A total of 610 consecutive patients were admitted to the universal bed unit and prospectively entered into the Society of Thoracic Surgeons National Cardiac Database. Intensive care unit level of care was determined by acuity and staffing needs. Telemetry was employed from admission to discharge, and multidisciplinary rounds were conducted twice daily. Postoperative outcomes were recorded during hospital stay, and comparisons were made with the Society of Thoracic Surgeons National Cardiac Database using identical variables over the same period of time. Results: Decreased ventilation time, intensive care unit and hospital stay, and reduction in the incidence of atrial fibrillation and infectious complications yielded a financial benefit in the universal bed group compared with the traditional model of admission. Stroke rate and in-hospital mortality were the same compared with regional and national centers. Compared with regional centers, there was an average cost savings between $6200 and $9500 per patient depending on the operation. Patient care satisfaction by independent survey was in the 99th percentile. Conclusions: The universal bed patient care model allows for expedient and efficacious care as measured by decreased length of intensive care unit and hospital stay, improved postoperative outcomes, patient satisfaction, and cost savings. (J Thorac Cardiovasc Surg 2012;143:475-81) C1 [Emaminia, Abbas; Corcoran, Phillip C.; Siegenthaler, Michael P.; Means, Melissa; Rasmussen, Sarah; Krause, Linda; Horvath, Keith A.] Suburban Hosp, Cardiothorac Surg Res Program, NIH, Ctr Heart, Bethesda, MD USA. [LaPar, Damien J.] Univ Virginia, Dept Surg, Charlottesville, VA USA. RP Horvath, KA (reprint author), Suburban Hosp, Cardiothorac Surg Res Program, NIH, Ctr Heart, 8600 Old Georgetown Rd, Bethesda, MD USA. EM horvathka@nhlbi.nih.gov NR 12 TC 3 Z9 3 U1 2 U2 9 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 475 EP 481 DI 10.1016/j.jtcvs.2011.10.001 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 879GP UT WOS:000299318000037 PM 22153858 ER PT J AU Wood, BJ Poon, RT Locklin, JK Dreher, MR Ng, KK Eugeni, M Seidel, G Dromi, S Neennan, Z Kolf, M Black, CDV Prabhakar, R Libutti, SK AF Wood, Bradford J. Poon, Ronnie T. Locklin, Julia K. Dreher, Matthew R. Ng, K. K. Eugeni, Michelle Seidel, Geoffrey Dromi, Sergio Neennan, Ziv Kolf, Michael Black, Christopher D. V. Prabhakar, Raj Libutti, Steven K. TI Phase I Study of Heat-Deployed Liposomal Doxorubicin during Radiofrequency Ablation for Hepatic Malignancies SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID TEMPERATURE SENSITIVE LIPOSOMES; COLORECTAL LIVER METASTASES; TUMOR XENOGRAFT MODEL; THERMAL ABLATION; DRUG-DELIVERY; HEPATOCELLULAR-CARCINOMA; LOCAL RECURRENCE; COAGULATION; CANCER; ACCUMULATION AB Purpose: A phase I dose escalation study was performed with systemically delivered lyso-thermosensitive liposomal doxorubicin (LTLD). The primary objectives were to determine the safe maximum tolerated dose (MTD), pharmacokinetic properties, and dose-limiting toxicity (DLT) of LTLD during this combination therapy. Materials and Methods: Subjects eligible for percutaneous or surgical radiofrequency (RF) ablation with primary (n = 9) or metastatic (n = 15) tumors of the liver, with four or fewer lesions as large as 7 cm in diameter, were included. RF ablation was initiated 15 minutes after starting a 30-minute intravenous LTLD infusion. Dose levels between 20 mg/m(2) and 60 mg/m(2) were evaluated. Magnetic resonance imaging, positron emission tomography, and computed tomography were performed at predetermined intervals before and after treatment until evidence of recurrence was seen, administration of additional antitumor treatment was performed, or a total of 3 years had elapsed. Results: DLT criteria were met at 60 mg/m(2), and the MTD was defined as 50 mg/m(2). RF ablation was performed during the peak of the plasma concentration time curve in an effort to yield maximal drug deposition. LTLD produced reversible, dose-dependent neutropenia and leukopenia. Conclusions: LTLD can be safely administered systemically at the MTD (50 mg/m(2)) in combination with RF ablation, with limited and manageable toxicity. Further evaluation of this agent combined with RF ablation is warranted to determine its role in the management of liver tumors. C1 [Wood, Bradford J.; Locklin, Julia K.; Dreher, Matthew R.; Dromi, Sergio; Neennan, Ziv] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Eugeni, Michelle; Seidel, Geoffrey; Kolf, Michael; Libutti, Steven K.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Seidel, Geoffrey] NCI, Clin Monitoring Res Program, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. [Black, Christopher D. V.; Prabhakar, Raj] Celsion, Lawrenceville, NJ USA. [Poon, Ronnie T.; Ng, K. K.] Univ Hong Kong, Queen Mary Hosp, Dept Surg, Hong Kong, Hong Kong, Peoples R China. RP Locklin, JK (reprint author), NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, 9000 Rockville Pk,Bldg 10,Room 1C364,MSC 1182, Bethesda, MD 20892 USA. EM locklinj@cc.nih.gov FU National Cancer Institute; National Institutes of Health (NIH) [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute and the Intramural Research Program of the National Institutes of Health (NIH), and is also supported by NIH/Celsion Cooperative Research Development Agreement 01974 and contract no. HHSN261200800001E. NR 35 TC 36 Z9 40 U1 2 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2012 VL 23 IS 2 BP 248 EP 255 DI 10.1016/j.jvir.2011.10.018 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 883TA UT WOS:000299656600016 PM 22178041 ER PT J AU Dreher, MR Sharma, KV Woods, DL Reddy, G Tang, YQ Pritchard, WF Chiesa, OA Karanian, JW Esparza, JA Donahue, D Levy, EB Willis, SL Lewis, AL Wood, BJ AF Dreher, Matthew R. Sharma, Karun V. Woods, David L. Reddy, Goutham Tang, Yiqing Pritchard, William F. Chiesa, Oscar A. Karanian, John W. Esparza, Juan A. Donahue, Danielle Levy, Elliot B. Willis, Sean L. Lewis, Andrew L. Wood, Bradford J. TI Radiopaque Drug-Eluting Beads for Transcatheter Embolotherapy: Experimental Study of Drug Penetration and Coverage in Swine SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID UNRESECTABLE HEPATOCELLULAR-CARCINOMA; RANDOMIZED CONTROLLED TRIAL; ARTERIAL EMBOLIZATION; TRANSARTERIAL CHEMOEMBOLIZATION; LIVER-TUMORS; HEPATIC MALIGNANCIES; RABBIT LIVER; IN-VITRO; MICROSPHERES; DOXORUBICIN AB Purpose: To determine local doxorubicin levels surrounding radiopaque drug-eluting beads (DEBs) in normal swine liver and kidney following transcatheter arterial chemoembolization. The influence of bead size (70-150 mu m or 100-300 mu m) was compared with regard to tissue penetration and spatial distribution of the bead, as well as eventual drug coverage (ie, amount of tissue exposed to drug). Materials and Methods: Radiopaque DEBs were synthesized by suspension polymerization followed by incorporation of iodized oil and doxorubicin. Chemoembolization of swine liver and kidney was performed under fluoroscopic guidance. Three-dimensional tissue penetration of "imageable" DEBs was investigated ex vivo with micro computed tomography (microCT). Drug penetration from the bead surface and drug coverage was evaluated with epifluorescence microscopy, and cellular localization of doxorubicin was evaluated with confocal microscopy. Necrosis was evaluated with hematoxylin and eosin staining. Results: MicroCT demonstrated that 70-150-mu m DEBs were present in more distal arteries and located in a more frequent and homogeneous spatial distribution. Tissue penetration of doxorubicin from the bead appeared similar (similar to 300 mu m) for both DEBs, with a maximum tissue drug concentration at 1 hour coinciding with nuclear localization of doxorubicin. The greater spatial frequency of the 70-150-mu m DEBs resulted in approximately twofold improved drug coverage in kidney. Cellular death is predominantly observed around the DEBs beginning at 8 hours, but increased at 24 and 168 hours. Conclusions: Smaller DEBs penetrated further into targeted tissue (ie, macroscopic) with a higher spatial density, resulting in greater and more uniform drug coverage (ie, microscopic) in swine. C1 [Dreher, Matthew R.; Sharma, Karun V.; Woods, David L.; Reddy, Goutham; Donahue, Danielle; Levy, Elliot B.; Wood, Bradford J.] NCI, Ctr Intervent Oncol, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Pritchard, William F.; Chiesa, Oscar A.; Karanian, John W.; Esparza, Juan A.] US FDA, Ctr Devices & Radiol Hlth, Laurel, MD USA. [Sharma, Karun V.] Georgetown Univ Hosp, Dept Radiol, Washington, DC 20007 USA. [Tang, Yiqing; Willis, Sean L.; Lewis, Andrew L.] Biocompatibles, Farnham, Surrey, England. RP Wood, BJ (reprint author), NCI, Ctr Intervent Oncol, Ctr Clin, NIH, 9000 Rockville Pike,Bldg 10,Room 1C341,MSC 1182, Bethesda, MD 20892 USA. EM bwood@nih.gov OI Lewis, Andrew/0000-0001-5779-5631 FU Biocompatibles (Farnham, UK); National Institutes of Health (NIH); Society of Interventional Radiology Foundation; United States Food and Drug Administration FX B.J.W. and M.R.D. received research support from Biocompatibles (Farnham, UK). ALL., S.L.W., and Y.T. are paid employees of Biocompatibles. None of the other authors have identified a conflict of interest.; This study was conducted in the Center for Interventional Oncology and is supported in part by the Intramural Research Program of the National Institutes of Health (NIH), the Society of Interventional Radiology Foundation Ring Grant, and an Interagency Agreement between the NIH and the United States Food and Drug Administration. NIH and Biocompatibles UK have a Cooperative Research and Development Agreement. NR 39 TC 26 Z9 27 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2012 VL 23 IS 2 BP 257 EP 264 DI 10.1016/j.jvir.2011.10.019 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 883TA UT WOS:000299656600017 PM 22178039 ER PT J AU Katsounas, A Trippler, M Wang, B Polis, M Lempicki, RA Kottilil, S Gerken, G Schlaak, JF AF Katsounas, A. Trippler, M. Wang, B. Polis, M. Lempicki, R. A. Kottilil, S. Gerken, G. Schlaak, J. F. TI CCL5 mRNA is a marker for early fibrosis in chronic hepatitis C and is regulated by interferon-alpha therapy and toll-like receptor 3 signalling SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE CCL5; fibrosis; HCV; IFN-a; stellate cells ID IMMUNE-RESPONSES; STELLATE CELLS; SURFACE EXPRESSION; CCR5 EXPRESSION; VIRUS-INFECTION; T-LYMPHOCYTES; CHEMOKINE; RANTES; LIVER; IFN AB . Mechanisms causing liver fibrosis during chronic hepatitis C virus infection (cHCV) are not sufficiently understood. This study was aimed to identify biomarkers for early fibrosis (EF) and to investigate their potential role in cHCV-related fibrogenesis. To this end, peripheral whole blood (PB) samples from 36 patients with cHCV recruited from two independent cohorts were subjected to microarray analysis 12 h before initiation of peginterferon-alpha (Peg-IFN-a) and ribavirin therapy. Liver biopsies were evaluated using the Batts-Ludwig staging (BL-S) classification system for fibrosis. We showed that gene expression profiles (N = 8) distinguished between EF (BL-S: 0,1) and late fibrosis (LF; BL-S: 2,3,4) with 88.9% accuracy. Fibrosis-related functional annotations for chemokine-C-C-motif ligand 5 (CCL5) provided foundation for focused investigation, and qRT-PCR confirmed that CCL5 mRNA levels (PB) reliably discriminate EF from LF (accuracy: 86.7%). Positive correlations (P < 0.05) with CCL5 mRNA levels and EF discovered gene expression profiles (PB) reflecting stable expression of IFN-a receptor 1, negative regulation of the MyD88-dependent toll-like receptor (TLR) pathway and decreased expression of TLR3 in vivo. Remarkably, Peg-IFN-a suppressed CCL5 mRNA levels (PB) in EF in vivo. These findings along with results from parallel in vitro investigation into the effect of IFN-a or poly I:C (TLR3-agonist) on CCL5 gene expression in hepatic stellate cells (HSC) attest to the multi-site involvement of these pathways in regulating fibrogenesis. In conclusion, we identified novel, reliable biomarkers for EF and exposed functional properties of the molecular network regulating CCL5 biosynthesis in peripheral or hepatic cell types with key roles in cHCV-related liver and/or immune pathogenesis. C1 [Katsounas, A.; Trippler, M.; Wang, B.; Gerken, G.; Schlaak, J. F.] Univ Hosp Essen, Dept Gastroenterol & Hepatol, D-45122 Essen, Germany. [Katsounas, A.; Lempicki, R. A.] NCI, Lab Immunopathogenesis & Bioinformat, SAIC Frederick Inc, Frederick, MD 21701 USA. [Polis, M.; Kottilil, S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Schlaak, JF (reprint author), Univ Hosp Essen, Dept Gastroenterol & Hepatol, Hufelandstr 55, D-45122 Essen, Germany. EM joerg.schlaak@uni-due.de RI Lempicki, Richard/E-1844-2012; OI Lempicki, Richard/0000-0002-7059-409X; Polis, Michael/0000-0002-9151-2268; Schlaak, Joerg/0000-0002-9499-1014 FU Association for the Promotion of Scientific Research and Science of the Clinic for Gastroenterology and Hepatology at the University Hospital Essen (Essen, NRW, Germany); National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This research was funded in part with funds from the Association for the Promotion of Scientific Research and Science of the Clinic for Gastroenterology and Hepatology at the University Hospital Essen (Essen, NRW, Germany) and in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. NR 41 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD FEB PY 2012 VL 19 IS 2 BP 128 EP 137 DI 10.1111/j.1365-2893.2011.01503.x PG 10 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 876HC UT WOS:000299097400035 PM 22239502 ER PT J AU Johnson, TR McLellan, JS Graham, BS AF Johnson, Teresa R. McLellan, Jason S. Graham, Barney S. TI Respiratory Syncytial Virus Glycoprotein G Interacts with DC-SIGN and L-SIGN To Activate ERK1 and ERK2 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN DENDRITIC CELLS; HEPATITIS-C VIRUS; CD4 T-CELLS; FUSION GLYCOPROTEIN; CYTOKINE PRODUCTION; IMMUNE-RESPONSES; INFECTION; PROTEIN; ATTACHMENT; HIV-1 AB Respiratory syncytial virus (RSV) interaction with epithelial and dendritic cells (DCs) is known to require divalent cations, suggesting involvement of C-type lectins. RSV infection and maturation of primary human DCs are reduced in a dose-dependent manner by EDTA. Therefore, we asked whether RSV infection involves DC-SIGN (CD209) or its isoform L-SIGN (CD299) (DC-SIGN/R). Using surface plasmon resonance analysis, we demonstrated that the attachment G glycoprotein of RSV binds both DC-and L-SIGN. However, neutralization of DC-and L-SIGN on primary human DCs did not inhibit RSV infection, demonstrating that interactions between RSV G and DC-or L-SIGN are not required for productive infection. Thus, neither DC-nor L-SIGN represents a functional receptor for RSV. However, inhibition of these interactions increased DC activation, as evidenced by significantly higher levels of alpha interferon (IFN-alpha), MIP-1 alpha, and MIP-1 beta in plasmacytoid DCs (pDCs) exposed to RSV after neutralization of DC-and L-SIGN. To understand the molecular interactions involved, intracellular signaling events triggered by purified RSV G glycoprotein were examined in DC-and L-SIGN-transfected 3T3 cells. RSV G interaction with DC- or L-SIGN was shown to stimulate ERK1 and ERK2 phosphorylation, with statistically significant increases relative to mock-infected cells. Neutralization of DC-and L-SIGN reduced ERK1/2 phosphorylation. With increased DC activation following DC- and L-SIGN neutralization and RSV exposure, these data demonstrate that the signaling events mediated by RSV G interactions with DC/L-SIGN are immunomodulatory and diminish DC activation, which may limit induction of RSV-specific immunity. C1 [Johnson, Teresa R.; Graham, Barney S.] NIAID, Viral Pathogenesis Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [McLellan, Jason S.] NIAID, Struct Biol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Johnson, TR (reprint author), NIAID, Viral Pathogenesis Lab, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tjohnson@genvec.com NR 61 TC 37 Z9 39 U1 1 U2 8 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 3 BP 1339 EP 1347 DI 10.1128/JVI.06096-11 PG 9 WC Virology SC Virology GA 879CT UT WOS:000299308000006 PM 22090124 ER PT J AU Stucker, KM Pagan, I Cifuente, JO Kaelber, JT Lillie, TD Hafenstein, S Holmes, EC Parrish, CR AF Stucker, Karla M. Pagan, Israel Cifuente, Javier O. Kaelber, Jason T. Lillie, Tyler D. Hafenstein, Susan Holmes, Edward C. Parrish, Colin R. TI The Role of Evolutionary Intermediates in the Host Adaptation of Canine Parvovirus SO JOURNAL OF VIROLOGY LA English DT Article ID FELINE PANLEUKOPENIA VIRUS; MINK ENTERITIS VIRUS; CAPSID STRUCTURE; MONOCLONAL-ANTIBODIES; TRANSFERRIN RECEPTORS; INFLUENZA-VIRUSES; RANGE; BINDING; DNA; TYPE-2 AB The adaptation of viruses to new hosts is a poorly understood process likely involving a variety of viral structures and functions that allow efficient replication and spread. Canine parvovirus (CPV) emerged in the late 1970s as a host-range variant of a virus related to feline panleukopenia virus (FPV). Within a few years of its emergence in dogs, there was a worldwide replacement of the initial virus strain (CPV type 2) by a variant (CPV type 2a) characterized by four amino acid differences in the capsid protein. However, the evolutionary processes that underlie the acquisition of these four mutations, as well as their effects on viral fitness, both singly and in combination, are still uncertain. Using a comprehensive experimental analysis of multiple intermediate mutational combinations, we show that these four capsid mutations act in concert to alter antigenicity, cell receptor binding, and relative in vitro growth in feline cells. Hence, host adaptation involved complex interactions among both surface-exposed and buried capsid mutations that together altered cell infection and immune escape properties of the viruses. Notably, most intermediate viral genotypes containing different combinations of the four key amino acids possessed markedly lower fitness than the wild-type viruses. C1 [Stucker, Karla M.; Kaelber, Jason T.; Lillie, Tyler D.; Parrish, Colin R.] Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Baker Inst Anim Hlth, Ithaca, NY 14853 USA. [Pagan, Israel; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Cifuente, Javier O.; Hafenstein, Susan] Penn State Univ, Coll Med, Div Infect Dis, Hershey, PA USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Parrish, CR (reprint author), Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Baker Inst Anim Hlth, Ithaca, NY 14853 USA. EM crp3@cornell.edu RI Pagan, Israel/H-1843-2015; Cifuente, Javier/F-3874-2016; OI Pagan, Israel/0000-0001-8876-1194; Cifuente, Javier/0000-0001-5420-121X; Kaelber, Jason/0000-0001-9426-1030; Holmes, Edward/0000-0001-9596-3552 FU National Institutes of Health (NIH) [AI28385, AI092571, GM080533, RR007059]; Marie Curie Fellowship [PIOF-GA-2009-236470] FX This work was supported by National Institutes of Health (NIH) grants AI28385 and AI092571 to C. R. P. and GM080533 to E. C. H. K. M. S. was supported by NIH training grant RR007059 to Douglas D. McGregor, and I. P. was supported by Marie Curie Fellowship PIOF-GA-2009-236470. NR 37 TC 17 Z9 18 U1 0 U2 13 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 3 BP 1514 EP 1521 DI 10.1128/JVI.06222-11 PG 8 WC Virology SC Virology GA 879CT UT WOS:000299308000021 PM 22114336 ER PT J AU Satheshkumar, PS Moss, B AF Satheshkumar, P. S. Moss, Bernard TI Sequence-Divergent Chordopoxvirus Homologs of the O3 Protein Maintain Functional Interactions with Components of the Vaccinia Virus Entry-Fusion Complex SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-CELL FUSION; SURFACE HEPARAN-SULFATE; MEMBRANE-PROTEIN; POXVIRUS ENTRY; HOST-CELLS; L1 PROTEIN; GENE; BINDS AB Composed of 35 amino acids, O3 is the smallest characterized protein encoded by vaccinia virus (VACV) and is an integral component of the entry-fusion complex (EFC). O3 is conserved with 100% identity in all orthopoxviruses except for monkeypox viruses, whose O3 homologs have 2 to 3 amino acid substitutions. Since O3 is part of the EFC, high conservation could suggest an immutable requirement for interaction with multiple proteins. Chordopoxviruses of other genera also encode small proteins with a characteristic predicted N-terminal alpha-helical hydrophobic domain followed by basic amino acids and proline in the same relative genome location as that of VACV O3. However, the statistical significance of their similarity to VACV O3 is low due to the large contribution of the transmembrane domain, their small size, and their sequence diversity. Nevertheless, trans-complementation experiments demonstrated the ability of a representative O3-like protein from each chordopoxvirus genus to rescue the infectivity of a VACV mutant that was unable to express endogenous O3. Moreover, recombinant viruses expressing O3 homologs in place of O3 replicated and formed plaques as well or nearly as well as wild-type VACV. The O3 homologs expressed by the recombinant VACVs were incorporated into the membranes of mature virions and, with one exception, remained stably associated with the detergent-extracted and affinity-purified EFC. The ability of the sequence-divergent O3 homologs to coordinate function with VACV entry proteins suggests the conservation of structural motifs. Analysis of chimeras formed by swapping domains of O3 with those of other proteins indicated that the N-terminal transmembrane segment was responsible for EFC interactions and for the complementation of infectivity. C1 [Satheshkumar, P. S.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM BMOSS@niaid.nih.gov FU Division of Intramural Research, NIAID, NIH FX This research was supported by the Division of Intramural Research, NIAID, NIH. NR 30 TC 6 Z9 6 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2012 VL 86 IS 3 BP 1696 EP 1705 DI 10.1128/JVI.06069-11 PG 10 WC Virology SC Virology GA 879CT UT WOS:000299308000036 PM 22114343 ER PT J AU Mehle, A Dugan, VG Taubenberger, JK Doudna, JA AF Mehle, Andrew Dugan, Vivien G. Taubenberger, Jeffery K. Doudna, Jennifer A. TI Reassortment and Mutation of the Avian Influenza Virus Polymerase PA Subunit Overcome Species Barriers SO JOURNAL OF VIROLOGY LA English DT Article ID SWINE-ORIGIN H1N1; A VIRUSES; MOLECULAR-BASIS; RNA-POLYMERASE; HIGH VIRULENCE; PANDEMIC H1N1; AMINO-ACID; HOST-RANGE; GENETIC COMPATIBILITY; CRYSTAL-STRUCTURE AB The emergence of new pandemic influenza A viruses requires overcoming barriers to cross-species transmission as viruses move from animal reservoirs into humans. This complicated process is driven by both individual gene mutations and genome reassortments. The viral polymerase complex, composed of the proteins PB1, PB2, and PA, is a major factor controlling host adaptation, and reassortment events involving polymerase gene segments occurred with past pandemic viruses. Here we investigate the ability of polymerase reassortment to restore the activity of an avian influenza virus polymerase that is normally impaired in human cells. Our data show that the substitution of human-origin PA subunits into an avian influenza virus polymerase alleviates restriction in human cells and increases polymerase activity in vitro. Reassortants with 2009 pandemic H1N1 PA proteins were the most active. Mutational analyses demonstrated that the majority of the enhancing activity in human PA results from a threonine-to-serine change at residue 552. Reassortant viruses with avian polymerases and human PA subunits, or simply the T552S mutation, displayed faster replication kinetics in culture and increased pathogenicity in mice compared to those containing a wholly avian polymerase complex. Thus, the acquisition of a human PA subunit, or the signature T552S mutation, is a potential mechanism to overcome the species-specific restriction of avian polymerases and increase virus replication. Our data suggest that the human, avian, swine, and 2009 H1N1-like viruses that are currently cocirculating in pig populations set the stage for PA reassortments with the potential to generate novel viruses that could possess expanded tropism and enhanced pathogenicity. C1 [Mehle, Andrew; Doudna, Jennifer A.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Doudna, Jennifer A.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. [Dugan, Vivien G.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Doudna, Jennifer A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA. RP Mehle, A (reprint author), Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. EM amehle@wisc.edu FU National Institute of General Medical Sciences [K99GM088484]; NIH; NIAID FX This work was supported in part by National Institute of General Medical Sciences grant K99GM088484 (to A.M.) and the Intramural Research Program of the NIH and the NIAID (to J.K.T.). NR 54 TC 48 Z9 49 U1 2 U2 10 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 3 BP 1750 EP 1757 DI 10.1128/JVI.06203-11 PG 8 WC Virology SC Virology GA 879CT UT WOS:000299308000041 PM 22090127 ER PT J AU Bessen, RA Wilham, JM Lowe, D Watschke, CP Shearin, H Martinka, S Caughey, B Wiley, JA AF Bessen, Richard A. Wilham, Jason M. Lowe, Diana Watschke, Christopher P. Shearin, Harold Martinka, Scott Caughey, Byron Wiley, James A. TI Accelerated Shedding of Prions following Damage to the Olfactory Epithelium SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSMISSIBLE MINK ENCEPHALOPATHY; UPPER RESPIRATORY-TRACT; RECEPTOR NEURONS; CELL-DEATH; NASAL-MUCOSA; INDUCED APOPTOSIS; NATURAL SCRAPIE; DOSE-RESPONSE; INFECTION; BULB AB In this study, we investigated the role of damage to the nasal mucosa in the shedding of prions into nasal samples as a pathway for prion transmission. Here, we demonstrate that prions can replicate to high levels in the olfactory sensory epithelium (OSE) in hamsters and that induction of apoptosis in olfactory receptor neurons (ORNs) in the OSE resulted in sloughing off of the OSE from nasal turbinates into the lumen of the nasal airway. In the absence of nasotoxic treatment, olfactory marker protein (OMP), which is specific for ORNs, was not detected in nasal lavage samples. However, after nasotoxic treatment that leads to apoptosis of ORNs, both OMP and prion proteins were present in nasal lavage samples. The cellular debris that was released from the OSE into the lumen of the nasal airway was positive for both OMP and the disease-specific isoform of the prion protein, PrPSc. By using the real-time quaking-induced conversion assay to quantify prions, a 100- to 1,000-fold increase in prion seeding activity was observed in nasal lavage samples following nasotoxic treatment. Since neurons replicate prions to higher levels than other cell types and ORNs are the most environmentally exposed neurons, we propose that an increase in ORN apoptosis or damage to the nasal mucosa in a host with a preexisting prion infection of the OSE could lead to a substantial increase in the release of prion infectivity into nasal samples. This mechanism of prion shedding from the olfactory mucosa could contribute to prion transmission. C1 [Bessen, Richard A.; Lowe, Diana; Watschke, Christopher P.; Shearin, Harold; Martinka, Scott; Wiley, James A.] Montana State Univ, Dept Immunol & Infect Dis, Bozeman, MT 59717 USA. [Wilham, Jason M.; Caughey, Byron] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Bessen, RA (reprint author), Montana State Univ, Dept Immunol & Infect Dis, Bozeman, MT 59717 USA. EM rbessen@montana.edu FU National Institutes of Health [R01 AI055043, R21 AI084094, P20 RR020185]; National Research Initiative of the USDA CSREES [2006-35201-16626]; Murphy Foundation; National Institute for Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by Public Health Service grants R01 AI055043, R21 AI084094, and P20 RR020185 from the National Institutes of Health, the National Research Initiative of the USDA CSREES grant 2006-35201-16626, and the Murphy Foundation. This work was supported in part by the Intramural Research Program of the National Institute for Allergy and Infectious Diseases, National Institutes of Health. NR 63 TC 13 Z9 13 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 3 BP 1777 EP 1788 DI 10.1128/JVI.06626-11 PG 12 WC Virology SC Virology GA 879CT UT WOS:000299308000044 PM 22130543 ER PT J AU San-Juan-Vergara, H Sampayo-Escobar, V Reyes, N Cha, B Pacheco-Lugo, L Wong, T Peeples, ME Collins, PL Castano, ME Mohapatra, SS AF San-Juan-Vergara, Homero Sampayo-Escobar, Viviana Reyes, Niradiz Cha, Byeong Pacheco-Lugo, Lisandro Wong, Terianne Peeples, Mark E. Collins, Peter L. Eugenia Castano, Maria Mohapatra, Shyam S. TI Cholesterol-Rich Microdomains as Docking Platforms for Respiratory Syncytial Virus in Normal Human Bronchial Epithelial Cells SO JOURNAL OF VIROLOGY LA English DT Article ID SMALL-MOLECULE INHIBITOR; PROTEIN-MEDIATED FUSION; SEMLIKI FOREST VIRUS; PLASMA-MEMBRANE; FLOW-CYTOMETRY; F-PROTEIN; LIPID MICRODOMAINS; MAMMALIAN-CELLS; INFECTED-CELLS; CILIATED CELLS AB Respiratory syncytial virus (RSV) is one of the major causes of respiratory infections in children, and it is the main pathogen causing bronchiolitis in infants. The binding and entry mechanism by which RSV infects respiratory epithelial cells has not yet been determined. In this study, the earliest stages of RSV infection in normal human bronchial epithelial cells were probed by tracking virions with fluorescent lipophilic dyes in their membranes. Virions colocalized with cholesterol-containing plasma membrane microdomains, identified by their ability to bind cholera toxin subunit B. Consistent with an important role for cholesterol in RSV infection, cholesterol depletion profoundly inhibited RSV infection, while cholesterol repletion reversed this inhibition. Merger of the outer leaflets of the viral envelope and the cell membrane appeared to be triggered at these sites. Using small-molecule inhibitors, RSV infection was found to be sensitive to Pak1 inhibition, suggesting the requirement of a subsequent step of cytoskeletal reorganization that could involve plasma membrane rearrangements or endocytosis. It appears that RSV entry depends on its ability to dock to cholesterol-rich microdomains (lipid rafts) in the plasma membrane where hemifusion events begin, assisted by a Pak1-dependent process. C1 [San-Juan-Vergara, Homero; Sampayo-Escobar, Viviana; Pacheco-Lugo, Lisandro; Eugenia Castano, Maria] Fdn Univ Norte, Dept Med, Barranquilla, Colombia. [San-Juan-Vergara, Homero; Wong, Terianne; Mohapatra, Shyam S.] Univ S Florida, Dept Internal Med, Div Translat Med, Nanomed Res Ctr, Tampa, FL 33612 USA. [Reyes, Niradiz] Univ Cartagena, Fac Med, Cartagena, Colombia. [Cha, Byeong] Univ S Florida, Coll Med, Lisa Muma Weitz Lab Adv Microscopy & Cell Imaging, Tampa, FL USA. [Pacheco-Lugo, Lisandro] Univ Simon Bolivar, Fac Med, Barranquilla, Colombia. [Peeples, Mark E.] Nationwide Childrens Hosp, Res Inst, Columbus, OH USA. [Peeples, Mark E.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA. [Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Mohapatra, Shyam S.] James Haley VA Hosp, Tampa, FL USA. RP San-Juan-Vergara, H (reprint author), Fdn Univ Norte, Dept Med, Barranquilla, Colombia. EM hsanjuan@uninorte.edu.co RI Mohapatra, Shyam/C-2500-2012; OI Pacheco-Lugo, Lisandro/0000-0002-9248-4596 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) [R01-AI075523]; VA Career Scientist Award; VA Merit Review Award; Colombian Administrative Department for Science, Technology and Innovation (COLCIENCIAS) [121540820542, 312-2007, 121549326215, 651-2009] FX This work was supported by a grant from the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID; R01-AI075523) to H.S.-J.-V. and S.S.M., by the VA Career Scientist Award and the VA Merit Review Award to S.S.M., and by two grants from the Colombian Administrative Department for Science, Technology and Innovation (COLCIENCIAS; code 121540820542, contract no. 312-2007; and code 121549326215, contract no. 651-2009). Neither sponsor had any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Peter L. Collins was supported by the NIAID Intramural Program. The authors declare no conflict of interest related to this work. NR 91 TC 23 Z9 24 U1 0 U2 8 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 3 BP 1832 EP 1843 DI 10.1128/JVI.06274-11 PG 12 WC Virology SC Virology GA 879CT UT WOS:000299308000049 PM 22090136 ER PT J AU Lambrechts, L Fansiri, T Pongsiri, A Thaisomboonsuk, B Klungthong, C Richardson, JH Ponlawat, A Jarman, RG Scott, TW AF Lambrechts, Louis Fansiri, Thanyalak Pongsiri, Arissara Thaisomboonsuk, Butsaya Klungthong, Chonticha Richardson, Jason H. Ponlawat, Alongkot Jarman, Richard G. Scott, Thomas W. TI Dengue-1 Virus Clade Replacement in Thailand Associated with Enhanced Mosquito Transmission SO JOURNAL OF VIROLOGY LA English DT Article ID PRIMARY-SCHOOL CHILDREN; LINEAGE REPLACEMENT; KAMPHAENG-PHET; AEDES-AEGYPTI; PUERTO-RICO; SELECTION; MICROEVOLUTION; EMERGENCE; EVOLUTION; STRAINS AB Dengue viruses (DENV) are characterized by extensive genetic diversity and can be organized in multiple, genetically distinct lineages that arise and die out on a regular basis in regions where dengue is endemic. A fundamental question for understanding DENV evolution is the relative extent to which stochastic processes (genetic drift) and natural selection acting on fitness differences among lineages contribute to lineage diversity and turnover. Here, we used a set of recently collected and archived low-passage DENV-1 isolates from Thailand to examine the role of mosquito vector-virus interactions in DENV evolution. By comparing the ability of 23 viruses isolated on different dates between 1985 and 2009 to be transmitted by a present-day Aedes aegypti population from Thailand, we found that a major clade replacement event in the mid-1990s was associated with virus isolates exhibiting increased titers in the vector's hemocoel, which is predicted to result in a higher probability of transmission. This finding is consistent with the hypothesis that selection for enhanced transmission by mosquitoes is a possible mechanism underlying major DENV clade replacement events. There was significant variation in transmission potential among isolates within each clade, indicating that in addition to vector-driven selection, other evolutionary forces act to maintain viral genetic diversity. We conclude that occasional adaptive processes involving the mosquito vector can drive major DENV lineage replacement events. C1 [Fansiri, Thanyalak; Pongsiri, Arissara; Richardson, Jason H.; Ponlawat, Alongkot] Armed Forces Res Inst Med Sci, Dept Entomol, Bangkok 10400, Thailand. [Lambrechts, Louis; Fansiri, Thanyalak] Inst Pasteur, Dept Virol, Paris, France. [Thaisomboonsuk, Butsaya; Klungthong, Chonticha; Jarman, Richard G.] Armed Forces Res Inst Med Sci, Dept Virol, Bangkok 10400, Thailand. [Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Lambrechts, L (reprint author), Armed Forces Res Inst Med Sci, Dept Entomol, Bangkok 10400, Thailand. EM louis.lambrechts@pasteur.fr RI Lambrechts, Louis/A-2057-2010; Richardson, Jason/A-9441-2011 OI Lambrechts, Louis/0000-0001-5958-2138; FU National Institutes of Health [R01 GM-083224]; French Agence Nationale de la Recherche [ANR-09-RPDOC-007-01]; Science and Technology Directorate, Department of Homeland Security, and Fogarty International Center, National Institutes of Health FX This study was primarily supported by grant R01 GM-083224 from the National Institutes of Health. L. L. was supported by grant ANR-09-RPDOC-007-01 from the French Agence Nationale de la Recherche. T. W. S. received support from the Research and Policy for Infectious Disease Dynamics Program of the Science and Technology Directorate, Department of Homeland Security, and Fogarty International Center, National Institutes of Health. NR 48 TC 42 Z9 43 U1 0 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2012 VL 86 IS 3 BP 1853 EP 1861 DI 10.1128/JVI.06458-11 PG 9 WC Virology SC Virology GA 879CT UT WOS:000299308000051 PM 22130539 ER PT J AU Liu, R Sui, XM Laditka, JN Church, TS Colabianchi, N Hussey, J Blair, SN AF Liu, Rui Sui, Xuemei Laditka, James N. Church, Timothy S. Colabianchi, Natalie Hussey, Jim Blair, Steven N. TI Cardiorespiratory Fitness as a Predictor of Dementia Mortality in Men and Women SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE PHYSICAL FITNESS; COGNITIVE FUNCTION; ALZHEIMER DISEASE; VASCULAR DEMENTIA; METS ID PHYSICAL-ACTIVITY; OLDER-ADULTS; LATE-LIFE; COGNITIVE FUNCTION; ALZHEIMER-DISEASE; APOLIPOPROTEIN-E; BLOOD-PRESSURE; EXERCISE TEST; BRAIN; RISK AB LIU, R., X. SUI, J. N. LADITKA, T. S. CHURCH, N. COLABIANCHI, J. HUSSEY, and S. N. BLAIR. Cardiorespiratory Fitness as a Predictor of Dementia Mortality in Men and Women. Med. Sci. Sports Exerc., Vol. 44, No. 2, pp. 253-259, 2012. There is evidence that physical activity may reduce the risk of developing Alzheimer disease and dementia. However, few reports have examined the physical activity-dementia association with objective measures of physical activity. Cardiorespiratory fitness (hereafter called fitness) is an objective reproducible measure of recent physical activity habits. Purpose: We sought to determine whether fitness is associated with lower risk for dementia mortality in women and men. Methods: We followed 14,811 women and 45,078 men, age 20-88 yr at baseline, for an average of 17 yr. All participants completed a preventive health examination at the Cooper Clinic in Dallas, TX, during 1970-2001. Fitness was measured with a maximal treadmill exercise test, with results expressed in maximal METs. The National Death Index identified deaths through 2003. Cox proportional hazards models were used to examine the association between baseline fitness and dementia mortality, adjusting for age, sex, examination year, body mass index, smoking, alcohol use, abnormal ECGs, and health status. Results: There were 164 deaths with dementia listed as the cause during 1,012,125 person-years of exposure. Each 1-MET increase in fitness was associated with a 14% lower adjusted risk of dementia mortality (95% confidence interval (CI) - 6%-22%). With fitness expressed in tertiles, adjusted hazard ratios (HRs) for those in the middle-and high-fitness groups suggest their risk of dementia mortality was less than half that of those in the lowest fitness group (HR = 0.44, CI = 0.26-0.74 and HR = 0.49, CI = 0.26-0.90, respectively). Conclusions: Greater fitness was associated with lower risk of mortality from dementia in a large cohort of men and women. C1 [Liu, Rui] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Sui, Xuemei; Blair, Steven N.] Univ S Carolina, Dept Exercise Sci, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Laditka, James N.] Univ N Carolina, Dept Publ Hlth Sci, Charlotte, NC 28223 USA. [Church, Timothy S.] Pennington Biomed Res Ctr, Lab Prevent Med, Baton Rouge, LA USA. [Colabianchi, Natalie; Hussey, Jim; Blair, Steven N.] Univ S Carolina, Dept Epidemiol & Biostat, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. RP Liu, R (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, 111 TW Alexan Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM liur2@niehs.nih.gov FU National Institutes of Health [AG06945, HL62508, R21DK088195] FX The study was supported by National Institutes of Health grants AG06945, HL62508, and R21DK088195. NR 32 TC 28 Z9 28 U1 2 U2 20 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 253 EP 259 DI 10.1249/MSS.0b013e31822cf717 PG 7 WC Sport Sciences SC Sport Sciences GA 879FY UT WOS:000299316300009 PM 21796048 ER PT J AU Butler, NS Moebius, J Pewe, LL Traore, B Doumbo, OK Tygrett, LT Waldschmidt, TJ Crompton, PD Harty, JT AF Butler, Noah S. Moebius, Jacqueline Pewe, Lecia L. Traore, Boubacar Doumbo, Ogobara K. Tygrett, Lorraine T. Waldschmidt, Thomas J. Crompton, Peter D. Harty, John T. TI Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection SO NATURE IMMUNOLOGY LA English DT Article ID CD4 T-CELLS; CHRONIC VIRAL-INFECTION; FALCIPARUM-MALARIA; CHABAUDI-CHABAUDI; IMMUNE-RESPONSES; ENDEMIC AREA; B-CELLS; YOELII; PERSISTENCE; EXHAUSTION AB Infection of erythrocytes with Plasmodium species induces clinical malaria. Parasite-specific CD4(+) T cells correlate with lower parasite burdens and severity of human malaria and are needed to control blood-stage infection in mice. However, the characteristics of CD4(+) T cells that determine protection or parasite persistence remain unknown. Here we show that infection of humans with Plasmodium falciparum resulted in higher expression of the inhibitory receptor PD-1 associated with T cell dysfunction. In vivo blockade of the PD-1 ligand PD-L1 and the inhibitory receptor LAG-3 restored CD4(+) T cell function, amplified the number of follicular helper T cells and germinal-center B cells and plasmablasts, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice. Thus, chronic malaria drives specific T cell dysfunction, and proper function can be restored by inhibitory therapies to enhance parasite control. C1 [Moebius, Jacqueline; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Butler, Noah S.; Pewe, Lecia L.; Harty, John T.] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. [Traore, Boubacar; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Dept Epidemiol Parasit Dis, Fac Med Pharm & Odontostomatol, Bamako, Mali. [Tygrett, Lorraine T.; Waldschmidt, Thomas J.; Harty, John T.] Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA. [Waldschmidt, Thomas J.; Harty, John T.] Univ Iowa, Interdisciplinary Grad Program Immunol, Iowa City, IA 52242 USA. RP Crompton, PD (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM pcrompton@niaid.nih.gov; john-harty@uiowa.edu RI Crompton, Peter/N-1130-2016 FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases; US National Institutes of Health [AI085515, AI42767]; Department of Microbiology, University of Iowa FX We thank the residents of Kambila, Mali, for their participation; F. Lund (University of Rochester) for C57BL/6 Aicda-/- mice lacking the immunoglobulin heavy-chain mu-chain secretory domain; D. A. A. Vignali (St. Jude Children's Research Hospital) for hybridoma clone C9B7W; and S. Perlman, N. Schmidt and V. Badovinac for comments. Supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, the US National Institutes of Health (for work in Mali; and AI085515 and AI42767 for work in the J.T.H. laboratory) and the Department of Microbiology, University of Iowa (for work in the J.T.H. laboratory). NR 50 TC 139 Z9 144 U1 6 U2 38 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 188 EP 195 DI 10.1038/ni.2180 PG 8 WC Immunology SC Immunology GA 879FL UT WOS:000299315000016 ER PT J AU Taveira-DaSilva, AM Alford, CE Levens, ED Kotz, HL Moss, J AF Taveira-DaSilva, Angelo M. Alford, Connie E. Levens, Eric D. Kotz, Herbert L. Moss, Joel TI Favorable Response to Antigonadal Therapy for a Benign Metastasizing Leiomyoma SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID LYMPHANGIOLEIOMYOMATOSIS; UTERUS AB BACKGROUND: Benign metastasizing leiomyoma and lymphangioleiomyomatosis (LAM) both are characterized by abnormal proliferation of smooth muscle-like cells in the lung. CASE: A 32-year-old African woman with a diagnosis of LAM underwent myomectomy for uterine leiomyomas. An alternative diagnosis of benign metastasizing leiomy oma was made on repeat lung biopsy. Treatment with leuprolide acetate decreased pulmonary infiltrates and improved lung function and exercise tolerance. CONCLUSION: Accurately diagnosing benign metastasizing leiomyoma has important implications for clinical outcome. Because its clinical presentation may be misleading, immunohistochemical techniques may assist in differentiating benign metastasizing leiomyoma from LAM. This is important because, in benign metastasizing leiomyoma, reduced tumor burden and improved pulmonary function may be achieved by suppressing gonadal steroids. (Obstet Gynecol 2012;119:438-42) DOI:10.1097/AOG.0b013e318240090e C1 [Taveira-DaSilva, Angelo M.] NHLBI, Cardiovasc & Pulm Branch, Program Reprod & Adult Endocrinol,NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Taveira-DaSilva, AM (reprint author), NHLBI, Cardiovasc & Pulm Branch, Program Reprod & Adult Endocrinol,NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA. EM dasilvaa@nhlbi.nih.gov FU NHLBI [protocol 96-H-0100] FX Supported in part by the Intramural Research Programs of NHLBI (protocol 96-H-0100), PRAE NICHD, NIH, Bethesda, MD. NR 8 TC 6 Z9 12 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2012 VL 119 IS 2 BP 438 EP 442 DI 10.1097/AOG.0b013e318240090e PN 2 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 883AH UT WOS:000299604500009 PM 22270431 ER PT J AU Kaushal, S Merideth, M Kopparthy, P Pulanic, TK Stratton, P AF Kaushal, Suhasini Merideth, Melissa Kopparthy, Pallavi Pulanic, Tajana Klepac Stratton, Pamela TI Treatment of Multifocal Bowen's Disease in Immunocompromised Women With Surgery and Topical Imiquimod SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Gynecologic-Investigation CY MAR 17-21, 2010 CL Orlando, FL SP Soc Gynecol Invest ID HIV-INFECTED PATIENTS; VULVAR INTRAEPITHELIAL NEOPLASIA; EXTERNAL ANOGENITAL WARTS; THERAPY; CREAM AB BACKGROUND: In human immunodeficiency virus (HIV)-infected women, Bowen's disease may be difficult to treat successfully with surgery alone. Imiquimod cream, effective in treating Bowen's disease in healthy women, may be a useful postsurgical treatment in immunocompromised women. CASES: Two HIV-infected women had both Bowen's disease and severe cervical dysplasia. In both cases, Bowen's disease, but not cervical dysplasia, recurred after surgical treatment. When treated with topical 5% imiquimod cream twice weekly for 4 months, 70-80% reduction in lesions were observed in both patients. Follow-up biopsies of remaining lesions were vulvar intraepithelial neoplasia 1. CONCLUSION: Imiquimod cream, in combination with surgical treatment, may be an appropriate strategy for treatment of Bowen's disease in HIV-infected and other immunocompromised women. (Obstet Gynecol 2012;119:442-4) DOI:10.1097/AOG.0b013e318236f1a0 C1 [Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. NHLBI, Hematol Branch, Med Genet Branch,Off Director, Natl Human Genome Res Inst,Intramural Off Rare Di, Bethesda, MD 20892 USA. RP Stratton, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bldg 10,Room 1-3140,10 Ctr Dr,MSC 7109, Bethesda, MD USA. EM strattop@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 11 TC 4 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2012 VL 119 IS 2 BP 442 EP 444 DI 10.1097/AOG.0b013e318236f1a0 PN 2 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 883AH UT WOS:000299604500010 PM 22270432 ER PT J AU Wu, M Chason, R Wong, M AF Wu, Mae Chason, Rebecca Wong, Michelle TI Raynaud's Phenomenon of the Nipple SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID VASOSPASM AB BACKGROUND: Raynaud's phenomenon is a well-described pathologic state in which there is episodic vasospasm followed by vasodilation. It is described most commonly in the digits but also has been shown to affect the nipple vasculature. Raynaud's phenomenon of the nipple may result in discontinuation of breastfeeding secondary to pain and disruption of the maternal-infant bonding process. CASES: We present the cases of two patients with painful breastfeeding associated with color changes of the nipple. Owing to a clinical presentation similar to fungal infections, the patients were treated repeatedly with antifungals before the correct diagnosis was made. Symptoms resolved with a course of nifedipine. CONCLUSION: Increased awareness in the obstetric field will lead to appropriate diagnoses, earlier treatment and relief, and more successful breastfeeding experiences. (Obstel Gynecol 2012;119:447-9) DOI: 10.1097/AOG.0b013e31822c9a73 C1 [Wu, Mae] Natl Naval Med Ctr, Dept Obstet & Gynecol, Bethesda, MD 20889 USA. Kennedy Shriver Natl Inst Child Hlth & Human Dev, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Wu, M (reprint author), Natl Naval Med Ctr, Dept Obstet & Gynecol, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM Mae.Wu@med.navy.mil NR 10 TC 2 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2012 VL 119 IS 2 BP 447 EP 449 DI 10.1097/AOG.0b013e31822c9a73 PN 2 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 883AH UT WOS:000299604500012 PM 22270434 ER PT J AU Maguire, M Lungu, A Gorden, P Cochran, E Stratton, P AF Maguire, Marcy Lungu, Andrea Gorden, Phillip Cochran, Elaine Stratton, Pamela TI Pregnancy in a Woman With Congenital Generalized Lipodystrophy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HUMAN LEPTIN; OBESITY; WOMEN AB BACKGROUND: Congenital generalized lipodystrophy is a rare disorder characterized by scant adipose tissue, profound leptin deficiency, and severe insulin resistance, resulting in multiple metabolic derangements, including hyperandrogenism, anovulation, and impaired fecundity. CASE: A young woman with congenital generalized lipodystrophy receiving leptin therapy experienced menarche, conceived spontaneously, and delivered a liveborn male neonate. CONCLUSION: Adipose tissue is important to normal female reproductive function. Leptin in particular appears to play a key role in adipose-mediated regulation of fertility. (Obstet Gynecol 2012;119:452-5) DOI: 10.1097/AOG.0b013e31822cecf7 C1 [Maguire, Marcy] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20814 USA. NIDDK, Diabet Endocrinol & Obes Branch, Bethesda, MD USA. RP Maguire, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, 1E-3140,Bldg 10 CRC,10 Ctr Dr, Bethesda, MD 20814 USA. EM maguiremf@mail.nih.gov FU Intramural NIH HHS [Z99 DK999999] NR 10 TC 7 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2012 VL 119 IS 2 BP 452 EP 455 DI 10.1097/AOG.0b013e31822cecf7 PN 2 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 883AH UT WOS:000299604500014 PM 22270436 ER PT J AU Rouleau, C Sancho, J Campos-Rivera, J Teicher, BA AF Rouleau, Cecile Sancho, Jose Campos-Rivera, Juanita Teicher, Beverly A. TI Endosialin expression in side populations in human sarcoma cell lines SO ONCOLOGY LETTERS LA English DT Article DE side populations; cancer stem cells; sarcoma marker ID CANCER STEM-CELLS; IN-VITRO; TUMOR-CELLS; HUMAN OSTEOSARCOMA; INITIATING CELLS; GROWTH; VIVO; IDENTIFICATION; GLYCOPROTEIN; CULTIVATION AB The Hoechst 33342 exclusion side population (SP) assay is a validated method used to identify cells with stem cell-like properties. When isolated from tumors, SP cells have been shown to have high malignant potential. SPs have been found in both carcinomas and sarcomas. The molecular profile of sarcoma SP is poorly understood. The purpose of the present study was to determine whether endosialin is a suitable therapeutic target for sarcomas. Six cell lines (HT-1080 fibrosarcoma, SJSA-1 and HOS osteosarcoma, A-673 and SK-ES-1 Ewing sarcoma) were used for the SP analysis. Flow cytometry was used to count and examine the cells. Results showed for the first time that endosialin (CD248), which was previously identified as a sarcoma marker, is expressed in sarcoma SP cells. This observation supports the hypothesis that endosialin is a promising therapeutic target for sarcomas. C1 [Rouleau, Cecile; Sancho, Jose; Campos-Rivera, Juanita; Teicher, Beverly A.] Genzyme Corp, Framingham, MA 01701 USA. RP Teicher, BA (reprint author), NCI, Dev Therapeut Program, 6130 Execut Blvd, Rockville, MD 20852 USA. EM beverly.teicher@nih.gov NR 38 TC 8 Z9 9 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-1074 J9 ONCOL LETT JI Oncol. Lett. PD FEB PY 2012 VL 3 IS 2 BP 325 EP 329 DI 10.3892/ol.2011.478 PG 5 WC Oncology SC Oncology GA 880KL UT WOS:000299405900016 ER PT J AU Knapp, KM Brogly, SB Muenz, DG Spiegel, HML Conway, DH Scott, GB Talbot, JT Shapiro, DE Read, JS AF Knapp, Katherine M. Brogly, Susan B. Muenz, Daniel G. Spiegel, Hans M. L. Conway, Daniel H. Scott, Gwendolyn B. Talbot, Jeffrey T. Shapiro, David E. Read, Jennifer S. CA P1025 Team Int Maternal Pediat TI Prevalence of Congenital Anomalies in Infants With In Utero Exposure to Antiretrovirals SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE congenital anomalies; in utero exposure; HIV; antiretroviral ID HIV-INFECTED WOMEN; IMMUNODEFICIENCY-VIRUS TYPE-1; BIRTH-DEFECTS; HIV-1-INFECTED WOMEN; ZIDOVUDINE TREATMENT; 1ST-TRIMESTER USE; THERAPY; TRANSMISSION; RISK; COMBINATION AB Background: Although use of efficacious interventions, including antiretrovirals (ARVs), has dramatically reduced the rate of mother-to-child transmission of human immunodeficiency virus, the safety of in utero ARV exposure remains of concern. Methods: Data regarding 1112 infants enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group protocol P1025 born between 2002 and 2007 were analyzed for this study. Congenital anomalies were classified based on the Metropolitan Atlanta Congenital Defects Program guidelines. Associations between congenital anomalies and timing of first in utero exposure to ARVs were evaluated by logistic regression analysis. Results: Congenital anomalies were identified and confirmed in 61 of the 1112 infants, resulting in a prevalence of 5.49/100 live births (95% confidence interval, 4.22-6.99). Among the 80 anomalies identified, the organ systems involved included cardiovascular (n = 33), musculoskeletal (n = 15), renal (n = 9), genitourinary (n = 6), craniofacial (n = 4), and central nervous system (n = 2). First trimester exposure to efavirenz was associated with a significantly increased risk of congenital anomalies (odds ratio, 2.84; 95% confidence interval, 1.13-7.16). No significant associations were observed between exposure to other individual ARVs or classes of ARVs started at any time during pregnancy and infant congenital anomalies. Conclusions: The observed rate of congenital anomalies in this cohort is higher than previously reported for the general population, but it is consistent with rates observed in other recent studies of children born to human immunodeficiency virus-infected women. Cardiovascular anomalies occurred most frequently. With the exception of a known teratogen (efavirenz), no statistically significant associations between in utero exposure to ARVs and congenital anomalies were identified. C1 [Knapp, Katherine M.] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. [Brogly, Susan B.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Muenz, Daniel G.; Talbot, Jeffrey T.; Shapiro, David E.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Spiegel, Hans M. L.] NIAID, Henry M Jackson Fdn Adv Mil Med, Prevent Sci Program, DAIDS,NIH, Bethesda, MD 20892 USA. [Conway, Daniel H.] Drexel Univ, Coll Med, St Christophers Hosp Children, Dept Pediat, Philadelphia, PA 19104 USA. [Scott, Gwendolyn B.] Univ Miami, Miller Sch Med, Div Pediat Infect Dis & Immunol, Miami, FL 33136 USA. [Shapiro, David E.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS PAMA Branch, NIH, Bethesda, MD USA. RP Knapp, KM (reprint author), St Jude Childrens Res Hosp, Dept Infect Dis, 262 Danny Thomas Pl,Mail Stop 600, Memphis, TN 38105 USA. EM katherine.knapp@stjude.org FU National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases [5 U01 AI41110, 1 U01 AI068616]; National Institute of Allergy and Infectious Diseases (NIAID); NICHD [N01-HD-9-001/HHSN267200800001C] FX The authors received funding support for the research on which this article is based from the National Institutes of Health (NIH). Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) (grant U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) (grant AI068632). This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement number 5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and number 1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-HD-9-001/HHSN267200800001C). The authors have no other funding or conflicts of interest to disclose. NR 34 TC 27 Z9 27 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD FEB PY 2012 VL 31 IS 2 BP 164 EP 170 DI 10.1097/INF.0b013e318235c7aa PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 879GA UT WOS:000299316500014 PM 21983213 ER PT J AU Lopez-Class, M Gomez-Duarte, J Graves, K Ashing-Giwa, K AF Lopez-Class, Maria Gomez-Duarte, Jessika Graves, Kristi Ashing-Giwa, Kimlin TI A contextual approach to understanding breast cancer survivorship among Latinas SO PSYCHO-ONCOLOGY LA English DT Review DE quality of life; Latinas; contextual-ecological perspective; breast cancer survivors ID QUALITY-OF-LIFE; TREATMENT DECISION-MAKING; SOCIAL SUPPORT; MULTIETHNIC SAMPLE; PHYSICAL-ACTIVITY; EXERCISE INTERVENTION; HEALTH PROMOTION; AFRICAN-AMERICAN; WHITE WOMEN; OLDER WOMEN AB Objectives: The purpose of this review is to describe the empirical literature on the health-related quality of life (HRQOL) in Latina breast cancer survivors by exploring the social determinants of health. In framing the key domains of survivors' quality of life within a ecological-contextual model that evaluates individual and societal contributions to health outcomes, we provide a comprehensive landscape of the diverse factors constituting Latina survivors' lived experiences and their resultant quality of life outcomes. Methods: We retrieved 244 studies via search engines and reference lists, of which 37 studies met the inclusion criteria. Results: Findings document the importance of the social determinants of HRQOL, with studies documenting ecological and contextual factors accounting for significant variance in HRQOL outcomes. Our review identifies a dearth of research examining community-, institutional-, and policy-level factors, such as health care access, legal and immigration factors, physical and built environments, and health care affordability and policies affecting Latina breast cancer survivors' HRQOL. Conclusions: Overall research on Latina breast cancer survivorship is sparse, with even greater underrepresentation within longitudinal and intervention studies. Results highlight a need for clear documentation of the comprehensive care needs of underserved cancer survivors and interventions considering integrated systems of care to address the medical and ecological factors known to impact the HRQOL of breast cancer survivors. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Lopez-Class, Maria] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Lopez-Class, Maria; Gomez-Duarte, Jessika; Graves, Kristi] Georgetown Univ, Med Ctr, Canc Control Program, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Lopez-Class, Maria; Gomez-Duarte, Jessika; Graves, Kristi] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. [Ashing-Giwa, Kimlin] Beckman Res Inst City Hope, Ctr Community Alliance Res & Educ, Duarte, CA USA. RP Lopez-Class, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Room 5C01, Bethesda, MD 20892 USA. EM lopezclassm@mail.nih.gov FU NCI [5U01CA114593-03]; Susan G. Komen for the Cure [POP0601292]; The Department of Defense [W81XWH-04-1-0548] FX This research was funded by NCI Grant # 5U01CA114593-03 (the Latin American Cancer Research Coalition) and Susan G. Komen for the Cure Grant # POP0601292 and The Department of Defense Award # W81XWH-04-1-0548. We would like to thank Ms. Susan Marx and Yasmin Salehizadeh for their assistance with manuscript preparation. NR 77 TC 17 Z9 17 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2012 VL 21 IS 2 BP 115 EP 124 DI 10.1002/pon.1998 PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 880NX UT WOS:000299415200002 PM 21674680 ER PT J AU Yu, SC Xiao, HL Jiang, XF Wang, QL Li, Y Yang, XJ Ping, YF Duan, JJ Jiang, JY Ye, XZ Xu, SL Xin, YH Yao, XH Chen, JH Chu, WH Sun, W Wang, B Wang, JM Zhang, X Bian, XW AF Yu, Shi-Cang Xiao, Hua-Liang Jiang, Xue-Feng Wang, Qing-Liang Li, Yan Yang, Xiao-Jun Ping, Yi-Fang Duan, Jiang Jie Jiang, Jian-Yong Ye, Xian-Zong Xu, Sen-Lin Xin, Yang-Hong Yao, Xiao-Hong Chen, Jian-Hong Chu, Wei-Hua Sun, Wei Wang, Bing Wang, Ji Ming Zhang, Xia Bian, Xiu-Wu TI Connexin 43 Reverses Malignant Phenotypes of Glioma Stem Cells by Modulating E-Cadherin SO STEM CELLS LA English DT Article DE Connexin 43; Glioma stem cells; E-Cadherin; Gap junctional intercellular communication; Invasiveness; Tumorigenicity ID JUNCTIONAL INTERCELLULAR COMMUNICATION; HUMAN GLIOBLASTOMA CELLS; BREAST-CANCER CELLS; BETA-CATENIN; GAP-JUNCTIONS; EPIGENETIC REGULATION; GENE-EXPRESSION; LUNG-CANCER; GROWTH; CX43 AB Malfunctioned gap junctional intercellular communication (GJIC) has been thought associated with malignant transformation of normal cells. However, the role of GJIC-related proteins such as connexins in sustaining the malignant behavior of cancer stem cells remains unclear. In this study, we obtained tumorspheres formed by glioma stem cells (GSCs) and adherent GSCs and then examined their GJIC. All GSCs showed reduced GJIC, and differentiated glioma cells had more gap junction-like structures than GSCs. GSCs expressed very low level of connexins, Cx43 in particular, which are key components of gap junction. We observed hypermethylation in the promoter of gap junction protein a1, which encodes Cx43 in GSCs. Reconstitution of Cx43 in GSCs inhibited their capacity of self-renewal, invasiveness, and tumorigenicity via influencing E-cadherin and its coding protein, which leads to changes in the expression of Wnt/beta-catenin targeting genes. Our results suggest that GSCs require the low expression of Cx43 for maintaining their malignant phenotype, and upregulation of Cx43 might be a potential strategy for treatment of malignant glioma. STEM CELLS 2012; 30:108-120. C1 [Yu, Shi-Cang; Xiao, Hua-Liang; Jiang, Xue-Feng; Wang, Qing-Liang; Yang, Xiao-Jun; Ping, Yi-Fang; Duan, Jiang Jie; Jiang, Jian-Yong; Ye, Xian-Zong; Xu, Sen-Lin; Xin, Yang-Hong; Yao, Xiao-Hong; Chen, Jian-Hong; Wang, Bing; Zhang, Xia; Bian, Xiu-Wu] Third Mil Med Univ, Inst Pathol, Southwest Hosp, Chongqing 400038, Peoples R China. [Yu, Shi-Cang; Xiao, Hua-Liang; Jiang, Xue-Feng; Wang, Qing-Liang; Yang, Xiao-Jun; Ping, Yi-Fang; Duan, Jiang Jie; Jiang, Jian-Yong; Ye, Xian-Zong; Xu, Sen-Lin; Xin, Yang-Hong; Yao, Xiao-Hong; Chen, Jian-Hong; Wang, Bing; Zhang, Xia; Bian, Xiu-Wu] Third Mil Med Univ, SW Canc Ctr, Southwest Hosp, Chongqing 400038, Peoples R China. [Li, Yan] Third Mil Med Univ, Cent Lab, Southwest Hosp, Chongqing 400038, Peoples R China. [Chu, Wei-Hua] Third Mil Med Univ, Dept Neurosurg, Southwest Hosp, Chongqing 400038, Peoples R China. [Sun, Wei] Third Mil Med Univ, Cent Lab, Chongqing 400038, Peoples R China. [Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. RP Bian, XW (reprint author), Third Mil Med Univ, Inst Pathol, Southwest Hosp, Chongqing 400038, Peoples R China. EM bianxiuwu@263.net RI Zhang, Xia/B-8152-2008; ye, xianzong/G-6079-2011; Li, Yan/O-7342-2016; Bian, Xiu-wu/D-4736-2017 OI Zhang, Xia/0000-0002-9040-1486; ye, xianzong/0000-0002-3640-0570; Bian, Xiu-wu/0000-0003-4383-0197 FU National Basic Research Program of China (973 Program) [2010CB529403]; National Natural Science Foundation of China (NSFC) [30725035, 30700863] FX This study was supported by grants from National Basic Research Program of China (973 Program, No. 2010CB529403) and the National Natural Science Foundation of China (NSFC, Nos. 30725035 and 30700863). NR 76 TC 28 Z9 31 U1 1 U2 18 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD FEB PY 2012 VL 30 IS 2 BP 108 EP 120 DI 10.1002/stem.1685 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 877UW UT WOS:000299209200003 PM 22131169 ER PT J AU Nemeth, K Wilson, T Rada, B Parmelee, A Mayer, B Buzas, E Falus, A Key, S Masszi, T Karpati, S Mezey, E AF Nemeth, Krisztian Wilson, Todd Rada, Balazs Parmelee, Alissa Mayer, Balazs Buzas, Edit Falus, Andras Key, Sharon Masszi, Tamas Karpati, Sarolta Mezey, Eva TI Characterization and Function of Histamine Receptors in Human Bone Marrow Stromal Cells SO STEM CELLS LA English DT Article DE Adult stem cells; Apoptosis; Bone marrow stromal cells; IL-6R; IL-6; Mesenchymal stem cells ID MESENCHYMAL STEM-CELLS; INNATE IMMUNITY; MAST-CELLS; MACROPHAGES; INFLAMMATION; EXPRESSION; DISEASE; MODEL; BETA AB There are several clinical trials worldwide using bone marrow stromal cells (BMSCs) as a cellular therapy to modulate immune responses in patients suffering from various inflammatory conditions. A deeper understanding of the molecular mechanisms involved in this modulatory effect could help us design better, more effective protocols to treat immune mediated diseases. In this study, we demonstrated that human BMSCs express H1, H2, and H4 histamine receptors and they respond to histamine stimulation with an increased interleukin 6 (IL-6) production both in vitro and in vivo. Using different receptor antagonists, we pinpointed the importance of the H1 histamine receptor, while Western blot analysis and application of various mitogen-activated protein kinase inhibitors highlighted the role of p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase kinases in the observed effect. When BMSCs were pretreated with either histamine or degranulated human mast cells, they exhibited an enhanced IL-6-dependent antiapoptotic effect on neutrophil granulocytes. Based on these observations, it is likely that introduction of BMSCs into a histamine-rich environment (such as any allergic setting) or pretreatment of these cells with synthetic histamine could have a significant modulatory effect on the therapeutic potential of BMSCs. STEM CELLS 2012; 30:222231. C1 [Wilson, Todd; Rada, Balazs] NIAID, Host Def Lab, NIH, Rockville, MD USA. [Buzas, Edit; Falus, Andras] Semmelweis Univ, Fac Med, Dept Genet Cell & Immunobiol, Budapest, Hungary. [Karpati, Sarolta] Semmelweis Univ, Dept Dermatovenereol & Dermatooncol, Budapest, Hungary. [Masszi, Tamas] Szent Laszlo Hosp, Dept Hematol & Stem Cell Transplantat, Budapest, Hungary. EM nemethk@mail.nih.gov; mezeye@mail.nih.gov RI Mayer, Balazs/B-7864-2013; OI Mayer, Balazs/0000-0003-3577-3823; Masszi, Tamas/0000-0002-9038-302X; Buzas, Edit/0000-0002-3744-206X FU DIR, NIDCR, of the IRP, NIH, DHHS FX We thank Dr. Dean Metcalfe for his help with the human mast cells and Dr. Tamas Balla for his guidance and help with calcium measurements. This work was supported by the DIR, NIDCR, of the IRP, NIH, DHHS. NR 37 TC 10 Z9 10 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD FEB PY 2012 VL 30 IS 2 BP 222 EP 231 DI 10.1002/stem.771 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 877UW UT WOS:000299209200014 PM 22045589 ER PT J AU Hannas, BR Lambright, CS Furr, J Evans, N Foster, PMD Gray, EL Wilson, VS AF Hannas, Bethany R. Lambright, Christy S. Furr, Johnathan Evans, Nicola Foster, Paul M. D. Gray, Earl L. Wilson, Vickie S. TI Genomic Biomarkers of Phthalate-Induced Male Reproductive Developmental Toxicity: A Targeted RT-PCR Array Approach for Defining Relative Potency SO TOXICOLOGICAL SCIENCES LA English DT Article DE mixture toxicity; antiandrogen; PPAR; phthalate risk assessment ID IN-UTERO EXPOSURE; FETAL-RAT TESTIS; N-BUTYL PHTHALATE; ALTERS SEXUAL-DIFFERENTIATION; DOSE-DEPENDENT ALTERATIONS; LEYDIG-CELL FUNCTION; DI(N-BUTYL) PHTHALATE; GENE-EXPRESSION; DIETHYLHEXYL PHTHALATE; DIISOBUTYL PHTHALATE AB Male rat fetuses exposed to certain phthalate esters (PEs) during sexual differentiation display reproductive tract malformations due to reductions in testosterone (T) production and the expression of steroidogenesis- and INSL3-related genes. In the current study, we used a 96-well real-time PCR array containing key target genes representing sexual determination and differentiation, steroidogenesis, gubernaculum development, and androgen signaling pathways to rank the relative potency of several PEs. We executed dose-response studies with diisobutyl (DIBP), dipentyl (DPeP), dihexyl (DHP), diheptyl (DHeP), diisononyl (DINP), or diisodecyl phthalate (DIDP) and serial dilutions of a mixture of nine phthalates. All phthalates, with the exception of DIDP, reduced fetal testicular T production. Several genes involved in cholesterol transport, androgen synthesis, and Insl3 also were downregulated in a dose-responsive manner by DIBP, DPeP, DHP, DHeP, DINP, and the 9-PE mixture. Despite speculation of peroxisome proliferator activated receptor (PPAR) involvement in the effects of PEs on the fetal testis, no PPAR-related genes were affected in the fetal testes by exposure to any of the tested PEs. Furthermore, the potent PPAR alpha agonist, Wy-14,643, did not reduce fetal testicular T production following gestational day 14-18 exposure, suggesting that the antiandrogenic activity of PEs is not PPAR alpha mediated. The overall sensitivity of the fetal endpoints (gene expression or T production) for the six phthalates from most to least was Cyp11b1 > Star = Scarb1 > Cyp17a1 = T production > Cyp11a1 = Hsd3b = Insl3 > Cyp11b2. The overall potency of the individual phthalates was DPeP > DHP > DIBP >= DHeP > DINP. Finally, the observed mixture interaction was adequately modeled by the dose-addition model for most of the affected genes. Together, these data advance our understanding of the collective reproductive toxicity of the PE compounds. C1 [Hannas, Bethany R.; Lambright, Christy S.; Furr, Johnathan; Evans, Nicola; Gray, Earl L.; Wilson, Vickie S.] US EPA, Reprod Toxicol Branch, Toxicol Assessment Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, Res Triangle Pk, NC 27711 USA. [Foster, Paul M. D.] NIEHS, Dept Hlth & Human Serv, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Gray, EL (reprint author), US EPA, Reprod Toxicol Branch, Toxicol Assessment Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, Mail Drop 72, Res Triangle Pk, NC 27711 USA. EM gray.earl@epa.gov OI Wilson, Vickie/0000-0003-1661-8481 FU United States Environmental Protection Agency; NTP at the National Institute of Environmental Health Sciences [75-92285501-1]; National Academy of Sciences FX This project was provided by an Interagency Agreement between the United States Environmental Protection Agency and the NTP at the National Institute of Environmental Health Sciences (IA no. 75-92285501-1) and B. R. H. was funded through a National Academy of Sciences postdoctoral fellowship. NR 59 TC 31 Z9 34 U1 5 U2 30 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2012 VL 125 IS 2 BP 544 EP 557 DI 10.1093/toxsci/kfr315 PG 14 WC Toxicology SC Toxicology GA 879QD UT WOS:000299346000021 PM 22112501 ER PT J AU Yuan, JP Lee, KP Hong, JH Muallem, S AF Yuan, J. P. Lee, K. P. Hong, J. H. Muallem, S. TI The closing and opening of TRPC channels by Homer1 and STIM1 SO ACTA PHYSIOLOGICA LA English DT Review DE Ca2+influx; Homer1; STIM1 ID METABOTROPIC GLUTAMATE RECEPTORS; OPERATED CALCIUM-ENTRY; STROMAL INTERACTION MOLECULE-1; FAST CA2+-DEPENDENT INACTIVATION; CAPACITATIVE CA2+ ENTRY; ACTIVATES CRAC CHANNELS; PANCREATIC ACINAR-CELL; PROTEIN SIGNALING RGS; PLASMA-MEMBRANE; INTRACELLULAR CALCIUM AB Influx of Ca2+ is a central component of the receptor-evoked Ca2+ signal. A ubiquitous form of Ca2+ influx comes from Ca2+ channels that are activated in response to depletion of the endoplasmic reticulum Ca2+ stores and are thus named the store-operated Ca2+-influx channels (SOCs). One form of SOC is the transient receptor potential canonical (TRPC) channels. A major question in the field of Ca2+ signalling is the molecular mechanism that regulates the opening and closing of these channels. All TRPC channels have a Homer-binding ligand and two conserved negative charges that interact with two terminal lysines of the stromal interacting molecule 1 (STIM1). The Homer and STIM1 sites are separated by only four amino acid residues. Based on available results, we propose a molecular mechanism by which Homer couples TRPC channels to IP3 receptors (IP3Rs) to keep these channels in the closed state. Dissociation of the TRPCs-Homer-IP3Rs complex allows STIM1 access to the TRPC channels negative charges to gate open these channels. C1 [Lee, K. P.; Hong, J. H.; Muallem, S.] NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Yuan, J. P.] Univ N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX USA. RP Muallem, S (reprint author), NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. EM joseph.yuan@unthsc.edu; shmuel.muallem@nih.gov FU NHLBI NIH HHS [K99 HL093297, R00 HL093297] NR 108 TC 32 Z9 33 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1748-1708 J9 ACTA PHYSIOL JI Acta Physiol. PD FEB PY 2012 VL 204 IS 2 SI SI BP 238 EP 247 DI 10.1111/j.1748-1716.2011.02319.x PG 10 WC Physiology SC Physiology GA 872EK UT WOS:000298791400011 PM 21518270 ER PT J AU Gadalla, SM Katki, HA Shebl, FM Giri, N Alter, BP Savage, SA AF Gadalla, Shahinaz M. Katki, Hormuzd A. Shebl, Fatma M. Giri, Neelam Alter, Blanche P. Savage, Sharon A. TI The relationship between DNA methylation and telomere length in dyskeratosis congenita SO AGING CELL LA English DT Article DE dyskeratosis congenita; epigenetic; human; methylation; telomere ID MARROW FAILURE SYNDROMES; MAMMALIAN TELOMERES; EPIGENETIC REGULATION; TINF2 MUTATIONS; HUMAN CANCER; ICF SYNDROME; HETEROCHROMATIN; CELLS; TRANSCRIPTION; COHORT AB The regulation of telomere length (TL) is a complex process, requiring the telomerase enzyme complex and numerous regulatory proteins. Epigenetic regulation may also be important in telomere maintenance. Specifically, methylation at subtelomeres is associated with changes in TL in vitro and in mouse models. Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by exceedingly short telomeres and mutations in telomere biology genes. To understand the interaction between methylation and TL in humans, we measured LINE-1, pericentromeric (NBL2), and subtelomeric (D4Z4) methylation in peripheral blood DNA derived from 40 patients with DC and 51 mutation-negative relatives. Pearsons correlation coefficient and linear regression models were used to evaluate the relationship between age-standardized lymphocyte TL measured by flow FISH and % DNA methylation. No differences in % subtelomeric, LINE-1, or pericentromeric methylation between patients with DC and relatives were noted except for an increase in % subtelomeric methylation in DC patients with a telomerase-complex mutation (TERC, TERT, DKC1, or TCAB1) (63.0% in DC vs. 61.8% in relatives, P = 0.03). Positive correlations between TL and DNA methylation at LINE-1 (r = 0.39, P = 0.01) and subtelomeric (r = 0.32, P = 0.05) sites were present in patients with DC. The positive correlation between TL and % LINE-1 methylation was restricted to TINF2 mutations. In contrast, statistically nonsignificant inverse correlations between TL and % LINE-1 (r = -0.17), subtelomeric (r = -0.20) were present in unaffected relatives. This study suggests an interaction between TL and both subtelomeric and LINE-1 methylation, which may be altered based on mutation status of telomere biology genes. C1 [Gadalla, Shahinaz M.; Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Gadalla, Shahinaz M.] NCI, Canc Prevent Fellowship Program, Rockville, MD 20852 USA. [Katki, Hormuzd A.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Shebl, Fatma M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 6120 Executive Blvd,EPS 7018, Rockville, MD 20852 USA. EM savagesh@mail.nih.gov RI Katki, Hormuzd/B-4003-2015; Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU National Cancer Institute; National Institutes of Health [N02-CP-11019, N02-CP-65504, N02-CP-65501] FX This work was funded by the intramural research program of the National Cancer Institute and National Institutes of Health. We thank the patients and their families for their generous participation in the study. Lisa Leathwood, RN, Westat, Inc. (NIH contracts N02-CP-11019, N02-CP-65504, and N02-CP-65501) provided outstanding study support. NR 27 TC 9 Z9 9 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD FEB PY 2012 VL 11 IS 1 BP 24 EP 28 DI 10.1111/j.1474-9726.2011.00755.x PG 5 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 875LN UT WOS:000299031500003 PM 21981348 ER PT J AU Bostrom, MA Kao, WHL Li, M Abboud, HE Adler, SG Iyengar, SK Kimmel, PL Hanson, RL Nicholas, SB Rasooly, RS Sedor, JR Coresh, J Kohn, OF Leehey, DJ Thornley-Brown, D Bottinger, EP Lipkowitz, MS Meoni, LA Klag, MJ Lu, LY Hicks, PJ Langefeld, CD Parekh, RS Bowden, DW Freedman, BI AF Bostrom, Meredith A. Kao, W. H. Linda Li, Man Abboud, Hanna E. Adler, Sharon G. Iyengar, Sudha K. Kimmel, Paul L. Hanson, Robert L. Nicholas, Susanne B. Rasooly, Rebekah S. Sedor, John R. Coresh, Josef Kohn, Orly F. Leehey, David J. Thornley-Brown, Denyse Bottinger, Erwin P. Lipkowitz, Michael S. Meoni, Lucy A. Klag, Michael J. Lu, Lingyi Hicks, Pamela J. Langefeld, Carl D. Parekh, Rulan S. Bowden, Donald W. Freedman, Barry I. CA Family Invest Nephropathy Diabet TI Genetic Association and Gene-Gene Interaction Analyses in African American Dialysis Patients With Nondiabetic Nephropathy SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE African American; APOL1; CFH; end-stage renal disease; Family Investigation of Nephropathy and Diabetes (FIND); focal segmental glomerulosclerosis (FSGS); hypertension ID STAGE RENAL-DISEASE; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; GENOME-WIDE ASSOCIATION; HEMOLYTIC-UREMIC SYNDROME; NEPHROTIC SYNDROME; SUSCEPTIBILITY LOCI; GLOMERULAR PROTEIN; KIDNEY-DISEASE; POLYMORPHISMS; MUTATIONS AB Background: African Americans have increased susceptibility to nondiabetic nephropathy relative to European Americans. Study Design: Follow-up of a pooled genome-wide association study (GWAS) in African American dialysis patients with nondiabetic nephropathy; novel gene-gene interaction analyses. Setting & Participants: Wake Forest sample: 962 African American nondiabetic nephropathy cases, 931 non-nephropathy controls. Replication sample: 668 Family Investigation of Nephropathy and Diabetes (FIND) African American nondiabetic nephropathy cases, 804 non-nephropathy controls. Predictors: Individual genotyping of top 1,420 pooled GWAS-associated single-nucleotide polymorphisms (SNPs) and 54 SNPs in 6 nephropathy susceptibility genes. Outcomes: APOL1 genetic association and additional candidate susceptibility loci interacting with or independently from APOL1. Results: The strongest GWAS associations included 2 noncoding APOL1 SNPs, rs2239785 (OR, 0.33; dominant; P = 5.9 x 10(-24)) and rs136148 (OR, 0.54; additive; P = 1.1 x 10(-7)) with replication in FIND (P = 5.0 x 10(-21) and 1.9 x 10(-05), respectively). rs2239785 remained associated significantly after controlling for the APOL1 G1 and G2 coding variants. Additional top hits included a CFH SNP (OR from meta-analysis in the 3,367 African American cases and controls, 0.81; additive; P = 6.8 x 10(-4)). The 1,420 SNPs were tested for interaction with APOL1 G1 and G2 variants. Several interactive SNPs were detected; the most significant was rs16854341 in the podocin gene (NPHS2; P = 0.0001). Limitations: Nonpooled GWASs have not been performed in African American patients with nondiabetic nephropathy. Conclusions: This follow-up of a pooled GWAS provides additional and independent evidence that APOL1 variants contribute to nondiabetic nephropathy in African Americans and identified additional associated and interactive nondiabetic nephropathy susceptibility genes. Am J Kidney Dis. 59(2): 210-221. (C) 2012 by the National Kidney Foundation, Inc. C1 [Bostrom, Meredith A.; Lu, Lingyi; Hicks, Pamela J.; Langefeld, Carl D.; Bowden, Donald W.; Freedman, Barry I.] Wake Forest Sch Med, Nephrol Sect, Winston Salem, NC 27157 USA. [Kao, W. H. Linda; Li, Man; Coresh, Josef; Meoni, Lucy A.; Klag, Michael J.; Parekh, Rulan S.] Johns Hopkins Univ, Baltimore, MD USA. [Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Adler, Sharon G.] Harbor UCLA Med Ctr, Los Angeles, CA USA. [Iyengar, Sudha K.; Sedor, John R.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Kimmel, Paul L.; Rasooly, Rebekah S.] NIDDK, NIH, Bethesda, MD USA. [Hanson, Robert L.] NIDDK, NIH, Phoenix, AZ USA. [Nicholas, Susanne B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kohn, Orly F.] Univ Chicago, Chicago, IL 60637 USA. [Leehey, David J.] Loyola Univ, Chicago, IL 60611 USA. [Thornley-Brown, Denyse] Univ Alabama, Birmingham, AL USA. [Bottinger, Erwin P.] Mt Sinai Sch Med, New York, NY USA. [Lipkowitz, Michael S.] Georgetown Univ, Sch Med, Washington, DC USA. [Parekh, Rulan S.] Univ Toronto, Toronto, ON, Canada. RP Freedman, BI (reprint author), Wake Forest Sch Med, Nephrol Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM bfreedma@wakehealth.edu RI Nelson, Robert/B-1470-2012; OI Rasooly, Rebekah/0000-0002-6357-5528 FU National Institutes of Health (NIH) [R01 DK 070941, R01 DK 084149, R01 DK53591, N01-HG-65403]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [F32 DK080617, DK07024]; FIND [U01DK57292, U01DK57329, U01DK057300, U01DK057298, U01DK057249, U01DK57295, U01DK070657, U01DK057303, U01DK57304]; NIH National Cancer Institute (NCI) [N01-CO-12400]; NIH-NCI Center for Cancer Research; National Center for Research Resources for the General Clinical Research Center; Case Western Reserve University [M01-RR-000080]; Wake Forest University [M01-RR-07122]; Harbor-University of California, Los Angeles Medical Center [M01-RR-00425]; College of Medicine, University of California, Irvine [M01-RR-00827-29]; University of New Mexico [HSC M01-RR-00997]; Frederic C. Bartter [M01-RR-01346]; Agency for Healthcare Research and Quality, Rockville, MD [HS08365]; National Heart, Lung, and Blood Institute, Bethesda, MD [HL62985] FX This study was supported in part by National Institutes of Health (NIH) grants R01 DK 070941 and R01 DK 084149 (Dr Freedman) and R01 DK53591 (Dr Bowden). Dr Bostrom was supported by F32 DK080617 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Computing resources were provided by the Wake Forest University Health Sciences Center for Public Health Genomics. This study was also supported by FIND grants U01DK57292, U01DK57329, U01DK057300, U01DK057298, U01DK057249, U01DK57295, U01DK070657, U01DK057303, U01DK070657, U01DK57304 and CHOICE study DK07024 from the NIDDK and in part by the Intramural Research Program of the NIDDK. This project has been funded in whole or in part with federal funds from the NIH National Cancer Institute (NCI) under contract N01-CO-12400 and the Intramural Research Program of the NIH-NCI Center for Cancer Research. This work also was supported by the National Center for Research Resources for the General Clinical Research Center grants: Case Western Reserve University, M01-RR-000080; Wake Forest University, M01-RR-07122; Harbor-University of California, Los Angeles Medical Center, M01-RR-00425; College of Medicine, University of California, Irvine, M01-RR-00827-29; University of New Mexico, HSC M01-RR-00997; and Frederic C. Bartter, M01-RR-01346. The CHOICE Study was supported in part by HS08365 from the Agency for Healthcare Research and Quality, Rockville, MD, and HL62985 from the National Heart, Lung, and Blood Institute, Bethesda, MD. Genotyping was performed by the Center for Inherited Disease Research, which is fully funded through a federal contract from the NIH to Johns Hopkins University (N01-HG-65403). NR 33 TC 21 Z9 21 U1 2 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 210 EP 221 DI 10.1053/j.ajkd.2011.09.020 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 879GK UT WOS:000299317500011 PM 22119407 ER PT J AU Textor, SC Gloviczki, ML Flessner, MF Calhoun, DA Glockner, J Grande, JP McKusick, MA Cha, SS Lerman, LO AF Textor, Stephen C. Gloviczki, Monika L. Flessner, Michael F. Calhoun, David A. Glockner, James Grande, Joseph P. McKusick, Michael A. Cha, Stephen S. Lerman, Lilach O. TI Association of Filtered Sodium Load With Medullary Volumes and Medullary Hypoxia in Hypertensive African Americans as Compared With Whites SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Hypertension; ethnicity; glomerular filtration rate (GFR); oxidative stress; blood oxygen level-dependent (BOLD) magnetic resonance (MR); hemodynamics ID STAGE RENAL-DISEASE; KIDNEY-DISEASE; GLOMERULAR-FILTRATION; OXIDATIVE STRESS; ANGIOTENSIN-II; BLOOD-PRESSURE; BIRTH-WEIGHT; BOLD-MRI; OXYGENATION; MEN AB Background: African Americans develop hypertension earlier with more target manifestations than whites despite having a higher glomerular filtration rate (GFR) for any level of serum creatinine. Study Design & Participants: This study tested the hypothesis that increased GFR and sodium reabsorption in African Americans is associated with increased metabolic work and medullary hypoxia in 49 nondiabetic patients with essential hypertension (29 whites and 20 African Americans) following a constant-sodium diet (150 mEq/d) and renin-angiotensin system blockade. Predictors: Ethnicity, age, measured GFR, sodium excretion, and body mass index. Outcomes: We examined cortical and medullary volumes and blood flows using multidetector computed tomography and intrarenal deoxyhemoglobin (R2*) using blood oxygen level-dependent magnetic resonance. Results: Blood pressure and sodium excretion were similar, whereas African Americans were more obese and had higher iothalamate GFRs. Renal cortical volumes did not differ, but medullary volumes adjusted for body size and age were higher in African Americans (32.3 +/- 11.2 vs 25.1 +/- 7.4 cm(3)/m(2) body surface area; P < 0.001). Sodium reabsorption and blood flows were higher in African Americans. Basal cortical deoxyhemoglobin values were similar between ethnic groups, whereas medullary R2* was higher in African Americans (39.7 +/- 5.1 vs 36.3 +/- 6.5/s; P = 0.02), but decreased to levels similar to whites after furosemide treatment. Levels of the circulating isoprostane prostaglandin F(2 alpha) were higher in African Americans and daily urinary prostaglandin F(2 alpha) excretion in African Americans correlated directly with renal blood flow (R = 0.71; P < 0.01). Limitations: Studies were limited to treated volunteers with normal kidney function without knowledge of prior nutrient intake. Conclusions: These data show for the first time that increased sodium reabsorption in obese African American patients with hypertension was associated with enlarged medullary volumes, functional hypoxia related to solute reabsorption, and a direct relationship between blood flows and urinary isoprostane levels. Our results support a model of increased oxygen consumption and oxidative stress in African Americans that may accelerate hypertension and target-organ injury compared with white patients with essential hypertension. Am J Kidney Dis. 59(2): 229-237. (C) 2012 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Textor, Stephen C.; Gloviczki, Monika L.; Glockner, James; Grande, Joseph P.; McKusick, Michael A.; Cha, Stephen S.; Lerman, Lilach O.] Mayo Clin, Rochester, MN 55905 USA. [Flessner, Michael F.] NIH, Bethesda, MD 20892 USA. [Flessner, Michael F.] Univ Mississippi, Jackson, MS 39216 USA. [Calhoun, David A.] Univ Alabama, Birmingham, AL USA. RP Textor, SC (reprint author), Mayo Clin, East 19,Mayo Bldg, Rochester, MN 55905 USA. EM textor.stephen@mayo.edu FU National Heart, Lung and Blood Institute (NHLBI) [PO1HL85307]; National Institutes of Health (NIH)/National Center for Research Resources [UL1 RR024150] FX The project described was supported by award PO1HL85307 from the National Heart, Lung and Blood Institute (NHLBI) and National Institutes of Health (NIH)/National Center for Research Resources CTSA grant UL1 RR024150. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NHLBI or the NIH. NR 41 TC 13 Z9 13 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2012 VL 59 IS 2 BP 229 EP 237 DI 10.1053/j.ajkd.2011.09.023 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 879GK UT WOS:000299317500013 PM 22130642 ER PT J AU Aung, PP Sarlomo-Rikala, M Lasota, J Lai, JP Wang, ZF Miettinen, M AF Aung, Phyu Phyu Sarlomo-Rikala, Maarit Lasota, Jerzy Lai, Jin-Ping Wang, Zeng-Feng Miettinen, Markku TI KBA62 and PNL2: 2 New Melanoma Markers-Immunohistochemical Analysis of 1563 Tumors Including Metastatic, Desmoplastic, and Mucosal Melanomas and Their Mimics SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE KBA62; PNL2; metastatic and desmoplastic melanoma; PEComa; immunohistochemistry ID SECTIONS; KBA.62 AB Identification of metastatic melanoma can be difficult because of its considerable morphologic variation and mimicry of a wide variety of other tumors. The more melanoma-specific melanoma markers, MelanA/MART-1, HMB45, and tyrosinase, used in addition to S100 protein, all have limitations in sensitivity and specificity. In this study, we evaluated 2 new melanoma markers, monoclonal antibodies KBA62 and PNL2 to yet unidentified antigens, using a large panel of metastatic melanomas (n = 214), desmoplastic melanomas (n = 34), gastrointestinal mucosal melanomas (n = 54), benign nevi (n = 27), clear cell sarcomas (n = 16), and nonmelanocytic tumors (n = 1218). Immunoreactivity for KBA62 and PNL2 was found in all pigmented nevi and in 86% and 90% of metastatic melanomas, respectively. Mucosal melanomas showed a similar rate of PNL2 immunoreactivity but somewhat less frequent KBA62 positivity (72%). In addition, KBA62 was found to be a sensitive diagnostic marker for desmoplastic melanoma (28 of 34; 82%), whereas PNL2 was only rarely positive (2 of 34; 6%). KBA62-positive normal tissues included pericytes, vascular and parenchymal smooth muscles, and basal cells of complex epithelia, including myoepithelia, whereas PNL2 labeled only melanocytes and neutrophils. Among nonmelanocytic tumors, those that were KBA62 positive were nodular fasciitis, leiomyoma and leiomyosarcoma, gastrointestinal stromal tumors, benign and malignant nerve sheath tumors, synovial sarcoma, and subsets of various carcinomas, especially those with squamous cell/stratified epithelial differentiation. PNL2 positivity in nonmelanocytic tumors was more restricted but occurred consistently in angiomyolipoma and other perivascular epitheloid cell tumor and in chronic myeloid leukemia tissue infiltrates. KBA62 may assist in the identification of desmoplastic melanomas, but its widespread occurrence in nonmelanomas limits utility. PNL2 is highly specific for melanomas but lacks reactivity with desmoplastic melanomas. It is also an excellent supplementary marker for perivascular epitheloid cell tumor at various sites. C1 [Miettinen, Markku] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Sarlomo-Rikala, Maarit] Helsinki Univ Hosp, Helsinki, Finland. [Sarlomo-Rikala, Maarit] HUSLab, Helsinki, Finland. RP Miettinen, M (reprint author), NCI, Pathol Lab, NIH, 10 Ctr Dr,Room 2B50, Bethesda, MD 20892 USA. EM miettinenmm@mail.nih.gov FU NIH/NCI FX This study was supported by the NIH/NCI Intramural Research Program. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 9 TC 14 Z9 15 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2012 VL 36 IS 2 BP 265 EP 272 DI 10.1097/PAS.0b013e31823651cb PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 879GD UT WOS:000299316800012 PM 22067329 ER PT J AU Ascierto, ML Kmieciak, M Idowu, MO Manjili, R Zhao, YD Grimes, M Dumur, C Wang, E Ramakrishnan, V Wang, XY Bear, HD Marincola, FM Manjili, MH AF Ascierto, Maria Libera Kmieciak, Maciej Idowu, Michael O. Manjili, Rose Zhao, Yingdong Grimes, Margaret Dumur, Catherine Wang, Ena Ramakrishnan, Viswanathan Wang, Xiang-Yang Bear, Harry D. Marincola, Francesco M. Manjili, Masoud H. TI A signature of immune function genes associated with recurrence-free survival in breast cancer patients SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer prognosis; Tumor relapse; Tumor microenvironment; Immune response; Neoadjuvant immunotherapy ID SUPPRESSOR-CELLS; T-CELLS; COLORECTAL-CANCER; PREDICTS; RECEPTOR; AMPLIFICATION; CHEMOTHERAPY; RECRUITMENT; METASTASIS; PROGNOSIS AB The clinical significance of tumor-infiltrating immune cells has been reported in a variety of human carcinomas including breast cancer. However, molecular signature of tumor-infiltrating immune cells and their prognostic value in breast cancer patients remain elusive. We hypothesized that a distinct network of immune function genes at the tumor site can predict a low risk versus high risk of distant relapse in breast cancer patients regardless of the status of ER, PR, or HER-2/neu in their tumors. We conducted retrospective studies in a diverse cohort of breast cancer patients with a 1-5 year tumor relapse versus those with up to 7 years relapse-free survival. The RNAs were extracted from the frozen tumor specimens at the time of diagnosis and subjected to microarray analysis and real-time RT-PCR. Paraffin-embedded tissues were also subjected to immunohistochemistry staining. We determined that a network of immune function genes involved in B cell development, interferon signaling associated with allograft rejection and autoimmune reaction, antigen presentation pathway, and cross talk between adaptive and innate immune responses were exclusively upregulated in patients with relapse-free survival. Among the 299 genes, five genes which included B cell response genes were found to predict with > 85% accuracy relapse-free survival. Real-time RT-PCR confirmed the 5-gene prognostic signature that was distinct from an FDA-cleared 70-gene signature of MammaPrint panel and from the Oncotype DX recurrence score assay panel. These data suggest that neoadjuvant immunotherapy in patients with high risk of relapse may reduce tumor recurrence by inducing the immune function genes. C1 [Kmieciak, Maciej; Manjili, Rose; Manjili, Masoud H.] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Microbiol & Immunol, Richmond, VA 23298 USA. [Ascierto, Maria Libera; Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Bethesda, MD 20892 USA. [Ascierto, Maria Libera; Wang, Ena; Marincola, Francesco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. [Idowu, Michael O.; Grimes, Margaret; Dumur, Catherine] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Pathol, Richmond, VA 23298 USA. [Zhao, Yingdong] NIH, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Ramakrishnan, Viswanathan] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Biostat, Richmond, VA 23298 USA. [Wang, Xiang-Yang] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA 23298 USA. [Bear, Harry D.] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Surg, Richmond, VA 23298 USA. RP Manjili, MH (reprint author), Virginia Commonwealth Univ, Massey Canc Ctr, Dept Microbiol & Immunol, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM mmanjili@vcu.edu RI Ascierto, Maria Libera/A-9239-2012 FU NIH [R01 CA104757]; Massey Cancer Center [2006FPP-04]; VCU; VCU Massey Cancer Center; Commonwealth Foundation for Cancer Research FX This study was supported by NIH R01 CA104757 Grant (M. H. Manjili), Massey Cancer Center Pilot Project Program 2006FPP-04 (M. H. Manjili), and VCU Technology Transfer Fund. We gratefully acknowledge the support of VCU Massey Cancer Center and the Commonwealth Foundation for Cancer Research. We thank Dr. K. Najarian for his review of the statistical analysis. NR 31 TC 48 Z9 50 U1 0 U2 4 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 871 EP 880 DI 10.1007/s10549-011-1470-x PG 10 WC Oncology SC Oncology GA 879QE UT WOS:000299346100014 PM 21479927 ER PT J AU Gartner, EM Silverman, P Simon, M Flaherty, L Abrams, J Ivy, P LoRusso, PM AF Gartner, Elaina M. Silverman, Paula Simon, Michael Flaherty, Lawrence Abrams, Judith Ivy, Percy LoRusso, Patricia M. TI A phase II study of 17-allylamino-17-demethoxygeldanamycin in metastatic or locally advanced, unresectable breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE 17-AAG; 17-allylamino-17-demethoxygeldanamycin; Breast cancer; Hsp90; Heat shock protein 90 ID REFRACTORY ADVANCED CANCERS; SOLID TUMORS; PEDIATRIC-PATIENTS; HSP90 INHIBITION; ADULT PATIENTS; TRIAL; EXPRESSION; 17-(ALLYLAMINO)-17-DEMETHOXYGELDANAMYCIN; HEAT-SHOCK-PROTEIN-90; ACTIVATION AB Heat shock protein 90 (Hsp90) is an attractive target for breast cancer treatment, as it is required for the proper folding and stabilization of several proteins known to be involved in breast cancer growth and development. These proteins include the epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), progesterone receptor (PR), and src. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is an intravenous Hsp90 inhibitor in development for breast cancer treatment. We conducted a phase II study of 17-AAG 220 mg/m(2) on days 1, 4, 8, and 11 every 21 days in patients with metastatic and locally advanced breast cancer. Since we expected the molecular effects of Hsp90 inhibition to extend beyond just ER, PR, and HER2 down regulation and to impact a variety of other cellular proteins, patients were not selected based on ER, PR, or HER2 status. Eleven patients, including 6 patients with triple negative breast cancer, were enrolled and treated. There were no responses and 3 patients had stable disease as their best response. Five patients developed grade 3/4 toxicities, which were primarily hepatic and pulmonary. Based on these results, we do not recommend further study of 17-AAG at this dosing schedule or in unselected breast cancer patients. C1 [Gartner, Elaina M.; Simon, Michael; Flaherty, Lawrence; Abrams, Judith; LoRusso, Patricia M.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. [Silverman, Paula] Case Western Reserve Univ, Univ Hosp Seidman Canc Ctr, Cleveland, OH 44106 USA. [Ivy, Percy] NCI, Canc Therapy Evaluat Program, NIH, Rockville, MD 20852 USA. RP Gartner, EM (reprint author), Wayne State Univ, Karmanos Canc Inst, 4100 John R,4HWCRC, Detroit, MI 48201 USA. EM gartnere@karmanos.org FU National Institutes of Health [U01 CA062487] FX This study was funded through a grant from the National Institutes of Health, U01 CA062487. NR 21 TC 35 Z9 35 U1 0 U2 3 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 933 EP 937 DI 10.1007/s10549-011-1866-7 PG 5 WC Oncology SC Oncology GA 879QE UT WOS:000299346100021 PM 22083229 ER PT J AU Neta, G Anderson, WF Gilbert, E Berrington, A AF Neta, Gila Anderson, William F. Gilbert, Ethel Berrington, Amy TI Variation in the risk of radiation-related contralateral breast cancer by histology and estrogen receptor expression in SEER SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Contralateral breast cancer; Radiotherapy; Estrogen receptor status; Histology ID ATOMIC-BOMB SURVIVORS; RANDOMIZED-TRIALS; HORMONAL-THERAPY; 15-YEAR SURVIVAL; POOLED ANALYSIS; RADIOTHERAPY; WOMEN; RECURRENCE; SUBTYPES AB Radiation exposure, particularly at a young age, is an established cause of breast cancer. It is not known whether radiation-related breast cancer risk varies by molecular subtype. We characterized the relative risk (RR) of contralateral breast cancer (CBC) related to radiotherapy by histology and estrogen receptor (ER) status of the CBC in five-year survivors in the Surveillance, Epidemiology, and End Results database using Poisson regression models adjusted for attained age and calendar year, age at and year of treatment, ER status of the first breast cancer, and disease stage. 205,316 female breast cancer survivors were followed for an average of 10 years from 1973 until 2007, during which time 6924 women developed a subsequent primary invasive breast cancer in the contralateral breast. The overall RR (and 95% confidence interval (CI)) of radiotherapy-related CBC was 1.11 (1.05-1.16). There was no heterogeneity in risk according to histology of the CBC (P > 0.50) for all ages or young age at exposure, but case numbers were small for subtypes other than ductal and lobular carcinomas. Information on ER status was available from 1990 onwards for 3546 CBC cases, of which 2597 (73%) were ER+ and 949 (27%) were ER-. The RRs were 1.10 (1.02-1.19) for ER+ CBC and 1.19 (1.04-1.35) for ER- CBC (P (difference) = 0.33). Among women treated age < 35 years, radiation-related risk of CBC was non-significantly elevated for ER- (RR = 1.38, 95% CI: 0.96-1.97) but not for ER+ tumors (RR = 0.80, 95% CI: 0.47-1.35) (P (difference) = 0.09). We did not find clear evidence that radiation-related risk varies by histology or ER status, but our findings, which were the first to examine this question, were suggestive of possible differences by ER status that may merit further investigation. C1 [Neta, Gila; Gilbert, Ethel; Berrington, Amy] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA. [Anderson, William F.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA. RP Neta, G (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20852 USA. EM netagil@mail.nih.gov FU NIH; Division of Cancer Epidemiology and Genetics at the National Cancer Institute FX This research was supported by the Intramural Research program of the NIH and the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. NR 23 TC 8 Z9 8 U1 0 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 1021 EP 1027 DI 10.1007/s10549-011-1820-8 PG 7 WC Oncology SC Oncology GA 879QE UT WOS:000299346100031 PM 22015617 ER PT J AU Simonyan, K Ludlow, CL AF Simonyan, Kristina Ludlow, Christy L. TI Abnormal Structure-Function Relationship in Spasmodic Dysphonia SO CEREBRAL CORTEX LA English DT Article DE cortical thickness; fMRI; laryngeal dystonia; VBM; voice production ID IDIOPATHIC CERVICAL DYSTONIA; WHITE-MATTER CHANGES; WRITERS CRAMP; BOTULINUM TOXIN; CORTICAL THICKNESS; CEREBRAL-CORTEX; FOCAL DYSTONIA; RHESUS-MONKEY; ACTIVATION; SPEECH AB Spasmodic dysphonia (SD) is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. Although recent studies have found abnormal brain function and white matter organization in SD, the extent of gray matter alterations, their structure-function relationships, and correlations with symptoms remain unknown. We compared gray matter volume (GMV) and cortical thickness (CT) in 40 SD patients and 40 controls using voxel-based morphometry and cortical distance estimates. These measures were examined for relationships with blood oxygen level-dependent signal change during symptomatic syllable production in 15 of the same patients. SD patients had increased GMV, CT, and brain activation in key structures of the speech control system, including the laryngeal sensorimotor cortex, inferior frontal gyrus (IFG), superior/middle temporal and supramarginal gyri, and in a structure commonly abnormal in other primary dystonias, the cerebellum. Among these regions, GMV, CT and activation of the IFG and cerebellum showed positive relationships with SD severity, while CT of the IFG correlated with SD duration. The left anterior insula was the only region with decreased CT, which also correlated with SD symptom severity. These findings provide evidence for coupling between structural and functional abnormalities at different levels within the speech production system in SD. C1 [Simonyan, Kristina] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Simonyan, Kristina] Mt Sinai Sch Med, Dept Otolaryngol, New York, NY 10029 USA. [Simonyan, Kristina; Ludlow, Christy L.] Natl Inst Neurol Disorders & Stroke, Laryngeal & Speech Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Ludlow, Christy L.] James Madison Univ, Dept Commun Sci & Disorders, Harrisonburg, VA 22807 USA. RP Simonyan, K (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM kristina.simonyan@mssm.edu OI Simonyan, Kristina/0000-0001-7444-0437; Ludlow, Christy/0000-0002-2015-6171 FU National Institute on Deafness and Other Communication Disorders; National Institutes of Health [R00DC009620]; National Institute of Neurological Disorders and Stroke [Z01NS00298] FX National Institute on Deafness and Other Communication Disorders; National Institutes of Health (R00DC009620 to K. S.); Intramural Program of National Institute of Neurological Disorders and Stroke (Z01NS00298 to C.L.L.). NR 54 TC 21 Z9 21 U1 2 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 417 EP 425 DI 10.1093/cercor/bhr120 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 876RD UT WOS:000299124400016 PM 21666131 ER PT J AU Kwon-Chung, KJ AF Kwon-Chung, Kyung J. TI Taxonomy of Fungi Causing Mucormycosis and Entomophthoramycosis (Zygomycosis) and Nomenclature of the Disease: Molecular Mycologic Perspectives SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID DISSEMINATED BASIDIOBOLOMYCOSIS; CONIDIOBOLUS-INCONGRUUS; UNITED-STATES; EVOLUTION; INFECTION; CLASSIFICATION; PHYLOGENY; INDONESIA; SPECTRUM; PATIENT AB Molecular phylogenetic analysis confirmed the phylum Zygomycota to be polyphyletic, and the taxa conventionally classified in Zygomycota are now distributed among the new phylum Glomeromycota and 4 subphyla incertae sedis (uncertain placement). Because the nomenclature of the disease zygomycosis was based on the phylum Zygomycota (Zygomycetes) in which the etiologic agents had been classified, the new classification profoundly affects the name of the disease. Zygomycosis was originally described as a convenient and inclusive name for 2 clinicopathologically different diseases, mucormycosis caused by members of Mucorales and entomophthoramycosis caused by species in the order Entomophthorales of Zygomycota. Without revision of original definition, the name "zygomycosis," however, has more often been used as a synonym only for mucormycosis. This article reviews the progress and changes in taxonomy and nomenclature of Zygomycota and the disease zygomycosis. The article also reiterates the reasons why the classic names "mucormycosis" and "entomophthoramycosis" are more appropriate than "zygomycosis.". C1 NIAID, Mol Microbiol Sect, LCID, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, LCID, NIH, 9000 Rockville Pike,Bldg 10,Room 11N234, Bethesda, MD 20892 USA. EM june_kwon-chung@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; Henry Schueler 419 Foundation FX This study was supported by funds from the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.; This article was published as part of a supplement entitled "Advances Against Mucormycosis: A Tribute to the Memory and Courage of Hank Schueler," sponsored by the Henry Schueler 41&9 Foundation. NR 40 TC 61 Z9 61 U1 0 U2 11 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 SU 1 BP S8 EP S15 DI 10.1093/cid/cir864 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 876GB UT WOS:000299094500003 PM 22247451 ER PT J AU Simone, CB Vapiwala, N Hampshire, MK Metz, JM AF Simone, Charles B., II Vapiwala, Neha Hampshire, Margaret K. Metz, James M. TI Cancer Patient Attitudes Toward Analgesic Usage and Pain Intervention SO CLINICAL JOURNAL OF PAIN LA English DT Article DE pain; analgesic; quality of life; Internet; cancer ID RADIATION ONCOLOGY PATIENTS; PHYSICIAN ATTITUDES; BREAST-CANCER; MANAGEMENT; BARRIERS; PREVALENCE; INTERNET; RELIEF; INFORMATION; MEDICATIONS AB Objectives: Although pain is commonly experienced by cancer patients, many receive inadequate pain management. Little data exist quantifying analgesic usage among oncology patients. This study evaluates perceived causes of pain and investigates reasons why oncology patients fail to receive optimal pain management. Methods: An institutional review board-approved questionnaire assessing pain control and analgesic usage was posted on OncoLink. Between November 2005 and July 2008, 1107 patients responded. Respondents were female (73%), white (74%), educated beyond high school (64%), and had surgery (69%), chemotherapy (64%), and radiation (47%). Most had breast (30%), gastrointestinal (12%), gynecologic (11%), and lung (8%) malignancies. Results: Sixty-seven percent of respondents reported pain, with 48% reporting pain directly from their cancer and 47% reporting pain from their cancer treatment. Among patients in pain, 25% did not use analgesics. Analgesic usage was significantly less in men (44% vs. 52%, P=0.023), minorities (42% vs. 53%, P=0.001), and patients with lower education levels (45% vs. 53%, P=0.013). Usage varied by cancer diagnosis and was higher among patients who received chemotherapy (56% vs. 40%, P<0.001) and radiation (53% vs. 47%, P=0.058). Reasons for not taking analgesics included: health care provider not recommending medications (85%), fearing addiction/ dependence (80%), and inability to pay (76%). Many patients reporting pain, not taking analgesics, pursued alternative therapies (94%). Discussion: Most cancer patients perceive pain from their disease or treatment, regardless of therapy received. Many, however, did not use analgesics due to concerns of addiction, cost, or lack of health care provider endorsement. Providers should regularly discuss pain symptoms and management with cancer patients. C1 [Simone, Charles B., II; Vapiwala, Neha; Hampshire, Margaret K.; Metz, James M.] Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Simone, Charles B., II] NCI, NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Simone, CB (reprint author), NCI, NIH, Radiat Oncol Branch, Bldg 10-CRC,Room B2-3500,10 Ctr Dr, Bethesda, MD 20892 USA. EM csimone@alumni.upenn.edu FU National Institutes of Health, National Cancer Institute, and Center for Cancer Research, Bethesda, MD FX Supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research, Bethesda, MD. The authors declare no conflict of interest. NR 48 TC 18 Z9 18 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD FEB PY 2012 VL 28 IS 2 BP 157 EP 162 DI 10.1097/AJP.0b013e318223be30 PG 6 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 879JO UT WOS:000299325700010 PM 21705874 ER PT J AU Shukla, S Schwartz, C Kapoor, K Kouanda, A Ambudkar, SV AF Shukla, Suneet Schwartz, Candice Kapoor, Khyati Kouanda, Abdul Ambudkar, Suresh V. TI Use of Baculovirus BacMam Vectors for Expression of ABC Drug Transporters in Mammalian Cells SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN P-GLYCOPROTEIN; NORMAL HUMAN-TISSUES; MULTIDRUG-RESISTANCE; RECOMBINANT BACULOVIRUS; MONOCLONAL-ANTIBODIES; CATALYTIC CYCLE; FUNCTIONAL-ROLE; ATP HYDROLYSIS; LOCALIZATION; DISCOVERY AB ATP-binding cassette (ABC) drug transporters ABCB1 [P-glycoprotein (Pgp)] and ABCG2 are expressed in many tissues including those of the intestines, the liver, the kidney and the brain and are known to influence the pharmacokinetics and toxicity of therapeutic drugs. In vitro studies involving their functional characteristics provide important information that allows improvements in drug delivery or drug design. In this study, we report use of the BacMam (baculovirus-based expression in mammalian cells) expression system to express and characterize the function of Pgp and ABCG2 in mammalian cell lines. BacMam-Pgp and BacMam-ABCG2 baculovirus-transduced cell lines showed similar cell surface expression (as detected by monoclonal antibodies with an external epitope) and transport function of these transporters compared to drug-resistant cell lines that overexpress the two transporters. Transient expression of Pgp was maintained in HeLa cells for up to 72 h after transduction (48 h after removal of the BacMam virus). These BacMam-baculovirus-transduced mammalian cells expressing Pgp or ABCG2 were used for assessing the functional activity of these transporters. Crude membranes isolated from these cells were further used to study the activity of these transporters by biochemical techniques such as photocross-linking with transport substrate and adenosine triphosphatase assays. In addition, we show that the BacMam expression system can be exploited to coexpress both Pgp and ABCG2 in mammalian cells to determine their contribution to the transport of a common anticancer drug substrate. Collectively, these data demonstrate that the BacMam-baculovirus-based expression system can be used to simultaneously study the transport function and biochemical properties of ABC transporters. C1 [Shukla, Suneet; Schwartz, Candice; Kapoor, Khyati; Kouanda, Abdul; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov RI shukla, suneet/B-4626-2012 FU National Institutes of Health National Cancer Institute; National Institutes of Health Center for Cancer Research; National Institutes of Health Office of Dietary Supplements [OD-09-101] FX This work was supported by the Intramural Research program of the National Institutes of Health National Cancer Institute; the National Institutes of Health Center for Cancer Research; and the National Institutes of Health Office of Dietary Supplements [Grant OD-09-101]. NR 33 TC 22 Z9 22 U1 0 U2 10 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD FEB PY 2012 VL 40 IS 2 BP 304 EP 312 DI 10.1124/dmd.111.042721 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 879KV UT WOS:000299329000011 PM 22041108 ER PT J AU Nagaoka, T Karasawa, H Castro, NP Rangel, MC Salomon, DS Bianco, C AF Nagaoka, Tadahiro Karasawa, Hideaki Castro, Nadia Pereira Rangel, Maria Cristina Salomon, David S. Bianco, Caterina TI An evolving web of signaling networks regulated by Cripto-1 SO GROWTH FACTORS LA English DT Article DE Cripto-1; Nodal-Cripto-1-dependent signaling pathway; MAPK/AKT signaling pathway; Notch; Wnt/beta-catenin ID MAMMARY EPITHELIAL-CELLS; LEFT-RIGHT ASYMMETRY; CANCER STEM-CELLS; A-P AXIS; MOUSE EMBRYO; TYROSINE PHOSPHORYLATION; VERTEBRATE DEVELOPMENT; MALIGNANT-MELANOMA; NODAL TRAFFICKING; XENOPUS EMBRYOS AB Over the past few decades, our understanding of the embryonic gene Cripto-1 has considerably advanced through biochemical, cell biology, and animal studies. Cripto-1 performs key functions during embryonic development, while it dramatically disappears in adult tissues, except possibly in adult tissue stem cells. Cripto-1 is re-expressed in human tumors promoting cell proliferation, migration, invasion, epithelial to mesenchymal transition, and tumor angiogenesis. This diversity of biological effects is dependent upon interaction of Cripto-1 with an extensive array of signaling molecules. In fact, Cripto-1 modulates signaling of transforming growth factor-beta family members, including Nodal, GDF-1/-3, Activin, and TGF-beta 1, activates c-src/MAPK/Protein Kinase B (AKT) pathway in a Glypican-1 and GRP78-dependent manner, and cross-talks with erb B4, Wnt/beta-catenin, Notch, Caveolin-1, and Apelin/putative receptor protein related to Angiotensin-type I receptor (APJ) pathways. This article provides an updated survey of the various signaling pathways modulated by Cripto-1 with a focus on mechanistic insights in our understanding of the biological function of Cripto-1 in eukaryotic cells. C1 [Nagaoka, Tadahiro; Karasawa, Hideaki; Castro, Nadia Pereira; Rangel, Maria Cristina; Salomon, David S.; Bianco, Caterina] NCI, Tumor Growth Factor Sect, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Bianco, C (reprint author), NCI, Tumor Growth Factor Sect, Lab Canc Prevent, NIH, 37 Convent Dr,Bldg 37,Room 1112, Bethesda, MD 20892 USA. EM biancoc@mail.nih.gov RI Rangel, Maria Cristina/P-7216-2014; OI Rangel, Maria Cristina/0000-0002-8002-9617; Nagaoka, Tadahiro/0000-0002-9391-0243 NR 66 TC 20 Z9 22 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0897-7194 J9 GROWTH FACTORS JI Growth Factors PD FEB PY 2012 VL 30 IS 1 BP 13 EP 21 DI 10.3109/08977194.2011.641962 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 875SA UT WOS:000299053800002 PM 22149969 ER PT J AU Zanotti-Fregonara, P Koroscil, TM Mantil, J Satter, M AF Zanotti-Fregonara, Paolo Koroscil, Thomas M. Mantil, Joseph Satter, Martin TI RADIATION DOSE TO THE FETUS FROM [F-18]-FDG ADMINISTRATION DURING THE SECOND TRIMESTER OF PREGNANCY SO HEALTH PHYSICS LA English DT Article DE dosimetry; internal; positron emission tomography; pregnancy; radiation; medical ID NUCLEAR-MEDICINE; F-18-FDG AB The authors estimated the fetal radiation dose from [F-18]-FDG in a rare case of a woman who underwent a PET/CT scan during the second trimester of pregnancy. The patient, a 27-y-old female with a paraganglioma, received 181.3 MBq [F-18]-FDG. From the concentrations of radioactivity measured on the images, the time-integrated activity coefficients of the fetus and the placenta were derived. The time-integrated activity coefficients of the mother's organs were taken from the standard values of ICRP publication 106. The final fetal dose was calculated using the 6-mo pregnant model of the OLINDA/EXM software. The fetus showed an overall low and homogeneous [F-18]-FDG uptake, with an average concentration of 2.41 kBq cm(-3). The uptake in the placenta was generally higher (average concentration = 3.69 kBq cm(-3)). The estimated time-integrated activity coefficients were 0.0130 and 0.0058 Bq h Bq(-1) for the fetus and the placenta, respectively. The final average dose to the fetus was 1.97 x 10(-2) mGy MBq(-1) (3.6 mGy in this patient who received 181.3 MBq). Therefore, the dose to the fetus from [F-18]-FDG administration during the second trimester of pregnancy is low. When medically indicated, pregnancy should not be a categorical basis for withholding [F-18]-FDG PET scans. Health Phys. 102(2):217-219; 2012 C1 [Zanotti-Fregonara, Paolo] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Koroscil, Thomas M.] Wright State Univ, Boonshoft Sch Med, Dayton, OH 45435 USA. [Mantil, Joseph; Satter, Martin] Kettering Med Ctr, Dept Nucl Med, PET, Dayton, OH USA. RP Zanotti-Fregonara, P (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B1D43,31 Ctr Dr,MSC 1026, Bethesda, MD 20892 USA. EM zanottifregonp@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS) FX The authors thank Michael G. Stabin for helpful discussion. This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS). NR 13 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2012 VL 102 IS 2 BP 217 EP 219 DI 10.1097/HP.0b013e318226ebb4 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 876LB UT WOS:000299107900011 PM 22217594 ER PT J AU Bharmal, N Tseng, CH Kaplan, R Wong, MD AF Bharmal, Nazleen Tseng, Chi-Hong Kaplan, Robert Wong, Mitchell D. TI State-Level Variations in Racial Disparities in Life Expectancy SO HEALTH SERVICES RESEARCH LA English DT Article DE Life expectancy; disparity; black; United States ID UNITED-STATES; HEALTH; MORTALITY AB Objective. To explore state patterns in the racial life expectancy gap. Data Sources. The 1997-2004 Multiple Cause of Death PUF, 2000 U.S. Census. Study Design. We calculated life expectancy at birth for black and white men and women. Data Extraction Methods. Data were obtained by the NCHS and U.S. Census Bureau. Principal Findings. States with small racial differences are due to higher-than-expected life expectancy for blacks or lower-than-expected for whites. States with large disparity are explained by higher-than-average life expectancy among whites or lower-than-average life expectancy among blacks. Conclusions. Heterogeneous state patterns in racial disparity in life expectancy exist. Eliminating disparity in states with large black populations would make the greatest impact nationally. C1 [Bharmal, Nazleen] Univ Calif Los Angeles, UCLA David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, AHA PRT Spina Outcomes Ctr, Los Angeles, CA 90095 USA. [Kaplan, Robert] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Bharmal, N (reprint author), Univ Calif Los Angeles, UCLA David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, AHA PRT Spina Outcomes Ctr, 710Westwood Plaza,C109 RNRC, Los Angeles, CA 90095 USA. EM nbharmal@mednet.ucla.edu OI Wong, Mitchell/0000-0002-4800-8410 FU Robert Wood Johnson Clinical Scholars Program; UCLA National Service [T32 PE19001] FX The authors wish to thank Martin Shapiro, M. D., Ph. D., for his help in the interpretation of the data, Patrick Heuveline, Ph. D., for his help in life table methods, and Jenny Kotlerman, Ph. D., for her help in programming codes. Dr. Bharmal was supported by the Robert Wood Johnson Clinical Scholars Program and UCLA National Service Research Award (T32 PE19001). NR 22 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2012 VL 47 IS 1 BP 544 EP 555 DI 10.1111/j.1475-6773.2011.01345.x PN 2 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 875OU UT WOS:000299041600014 PM 22092060 ER PT J AU Rutledge, HR Jiang, W Yang, J Warg, LA Schwartz, DA Pisetsky, DS Yang, IV AF Rutledge, Holly R. Jiang, Weiwen Yang, Jun Warg, Laura A. Schwartz, David A. Pisetsky, David S. Yang, Ivana V. TI Gene expression profiles of RAW264.7 macrophages stimulated with preparations of LPS differing in isolation and purity SO INNATE IMMUNITY LA English DT Article DE Lipopolysaccharide; endotoxin; LPS preparation; macrophage; gene expression; microarray ID SALMONELLA-ENTERITIDIS; IDENTIFICATION; LIPOPOLYSACCHARIDE; INFLAMMATION; MICE; PERSISTENCE; ACTIVATION; INFECTION; DISEASE; TRAM AB Lipopolysaccharide is a major component of the cell wall of Gram-negative bacteria and a potent stimulator of innate immune response via TLR4. Studies on the LPS action both in vivo and in vitro have used different preparations of LPS, including ultra-pure LPS (LIST) and a less pure but less expensive form (Sigma) isolated from Escherichia coli serotype O111:B4. The difference between the effects of these compounds has not been well studied although this information is important in understanding TLR stimulation. In this study, we compared response of RAW264.7 macrophage cells treated LIST or Sigma LPS for 6 h and 24 h. Gene expression data were analyzed to identify specific genes and pathways that are in common and unique to the two LPS preparations. Seven hundred fifty-five genes were differentially expressed at 6 h in response to Sigma LPS and 973 were differentially expressed following LIST LPS treatment, with 503 in common. At 24 h, Sigma LPS induced or repressed 901 genes while 1646 genes were differentially regulated by LIST LPS treatment; 701 genes were shared by two forms of LPS. Although considerably more genes were differentially expressed in response to LIST LPS, similar molecular pathways and transcriptional networks were activated by the two LPS preparations. We also treated bone marrow-derived macrophages (BMMs) from three strains of mice with different concentrations of LIST and Sigma LPS and showed that BMMs produced more IL-6 and TNF-alpha in response to LIST LPS at low LPS concentrations but, at higher LPS concentrations, more cytokines were produced in response to stimulation by Sigma LPS. Together, these findings suggest that, despite activation of similar molecular pathways by LIST and Sigma LPS preparations, residual protein impurities in the Sigma LPS preparation may nevertheless influence the transcriptional profile attributed to TLR4 stimulation. C1 [Warg, Laura A.; Schwartz, David A.; Yang, Ivana V.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Warg, Laura A.; Schwartz, David A.; Yang, Ivana V.] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO 80206 USA. [Schwartz, David A.; Yang, Ivana V.] Univ Colorado Denver, Dept Med, Aurora, CO USA. [Jiang, Weiwen; Pisetsky, David S.] Durham VA Med Ctr, Med Res Serv, Durham, NC USA. [Jiang, Weiwen; Pisetsky, David S.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Rutledge, Holly R.; Yang, Jun] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Yang, IV (reprint author), Natl Jewish Hlth, Dept Med, 1400 Jackson St,Smith Bldg A651, Denver, CO 80206 USA. EM yangi@njhealth.org FU NIH; National Institute of the Environmental Health Sciences; National Heart Lung and Blood Institute; VA Merit review FX This study was funded by the Intramural Research Program of the NIH, National Institute of the Environmental Health Sciences and National Heart Lung and Blood Institute, and a VA Merit review grant. NR 32 TC 7 Z9 7 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-4259 J9 INNATE IMMUN-LONDON JI Innate Immun. PD FEB PY 2012 VL 18 IS 1 BP 80 EP 88 DI 10.1177/1753425910393540 PG 9 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 877FL UT WOS:000299162600008 PM 21239457 ER PT J AU Singh, UP Singh, NP Busbee, B Guan, H Singh, B Price, RL Taub, DD Mishra, MK Nagarkatti, M Nagarkatti, PS AF Singh, Udai P. Singh, Narendra P. Busbee, Brandon Guan, H. Singh, Balwan Price, Robert L. Taub, Dennis D. Mishra, Manoj K. Nagarkatti, Mitzi Nagarkatti, Prakash S. TI Alternative Medicines as Emerging Therapies for Inflammatory Bowel Diseases SO INTERNATIONAL REVIEWS OF IMMUNOLOGY LA English DT Review DE bromelain; Crohn disease (CD); curcumin; inflammation; inflammatory bowel disease (IBD); polyphenols; pomegranate; resveratrol; rutin; ulcerative colitis (UC) ID AVIUM SUBSP PARATUBERCULOSIS; GENOME-WIDE ASSOCIATION; NF-KAPPA-B; RICH POMEGRANATE EXTRACT; ACTIVE CROHNS-DISEASE; ULTRAVIOLET-INDUCED PIGMENTATION; CHIMERIC MONOCLONAL-ANTIBODY; INDUCED EXPERIMENTAL COLITIS; RANDOMIZED CONTROLLED-TRIAL; CHEMOKINE RECEPTOR CXCR3 AB Inflammatory bowel disease (IBD) can be divided into two major categories, ulcerative colitis (UC) and Crohn disease (CD). While the main cause(s) of IBD remain unknown, a number of interventional and preventive strategies have been proposed for use against CD and UC. Many reports have focused on the use of alternative natural medicines as potential therapeutic interventions in IBD patients with minimal side effects. While the use of alternative medicines may be effective in IBD patients that are refractory to corticosteroids or thiopurins, alternative treatment strategies are limited and require extensive clinical testing before being optimized for use in patients. C1 [Singh, Udai P.; Singh, Narendra P.; Busbee, Brandon; Guan, H.] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. [Singh, Balwan] Emory Univ, Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Price, Robert L.] Univ S Carolina, Dept Cell & Dev Biol, Columbia, SC 29208 USA. [Taub, Dennis D.] NIA IRP, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. [Mishra, Manoj K.] Alabama State Univ, Dept Biol & Math Sci, Montgomery, AL 36101 USA. RP Singh, UP (reprint author), Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. EM Udai.singh@uscmed.sc.edu; taubd@grc.nia.nih.gov FU NIH [P01AT003961]; National Institute on Aging, NIH FX This study was supported in part by grants from NIH P01AT003961 and the Intramural Research Program, National Institute on Aging, NIH. NR 184 TC 11 Z9 11 U1 0 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0883-0185 EI 1563-5244 J9 INT REV IMMUNOL JI Int. Rev. Immunol. PD FEB PY 2012 VL 31 IS 1 BP 66 EP 84 DI 10.3109/08830185.2011.642909 PG 19 WC Immunology SC Immunology GA 877IT UT WOS:000299171900005 PM 22251008 ER PT J AU Gardner, ER Kelly, M Springman, E Lee, KJ Li, HQ Moore, W Figg, WD AF Gardner, Erin R. Kelly, Martha Springman, Eric Lee, Kyoung-jin Li, Haiqing Moore, William Figg, William D. TI Antiangiogenic and antitumor activity of LP-261, a novel oral tubulin binding agent, alone and in combination with bevacizumab SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Anticancer agent; Tubulin; In vitro; In vivo ID PROSTATE-CANCER; PACLITAXEL AB LP-261 is a novel tubulin targeting anticancer agent that binds at the colchicine site on tubulin, inducing G2/M arrest. Screening in the NCI60 cancer cell lines resulted in a mean GI50 of approximately 100 nM. Here, we report the results of testing in multiple mouse xenograft models and angiogenesis assays, along with bioavailability studies. To determine the antiangiogenic activity of LP-261, both in vitro and ex vivo experiments were performed. Human Umbilical Vein Endothelial cells (HUVECs) were incubated with LP-261 at 50 nM to 10 mu M. LP-261 was also tested in a rat aortic ring assay, from 20 nM to 10 mu M. Multiple mouse xenograft studies were performed to assess in vivo antitumor activity. LP-261 was tested as a single agent in colon adenocarcinoma (SW620) and prostate cancer (LNCaP and PC3) xenografts, evaluating several different dosing schedules. LP-261 was also used in combination with bevacizumab in the SW620 xenograft model. LP-261 also exhibited high oral bioavailability and apparent lack of efflux by intestinal transporters such as ABCB1. LP-261 is a very potent inhibitor of angiogenesis, preventing microvessel outgrowth in the rat aortic ring assay and HUVEC cell proliferation at nanomolar concentrations. Complete inhibition of tumor growth was achieved in the PC3 xenograft model and shown to be schedule dependent. Excellent inhibition of tumor growth in the SW620 model was observed, comparable with paclitaxel. Combining oral, low dose LP-261 with bevacizumab led to significantly improved tumor inhibition. Oral LP-261 is very effective at inhibiting tumor growth in multiple mouse xenograft models and is well tolerated. C1 [Li, Haiqing; Figg, William D.] NCI, Med Oncol Branch, Mol Pharmacol Sect, Bethesda, MD 20892 USA. [Gardner, Erin R.] NCI, Clin Pharmacol Program, SAIC Frederick, Frederick, MD 21702 USA. [Kelly, Martha; Springman, Eric; Lee, Kyoung-jin; Moore, William] Ansaris, Blue Bell, PA 19422 USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, Mol Pharmacol Sect, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU National Cancer Institute, National Institutes of Health [N01-CO-12400, HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400 and HHSN261200800001E.1 The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.; This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 10 TC 3 Z9 3 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2012 VL 30 IS 1 BP 90 EP 97 DI 10.1007/s10637-010-9520-5 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 876QC UT WOS:000299121500009 PM 20820910 ER PT J AU Kim, GP Mahoney, MR Szydlo, D Mok, TSK Marshke, R Holen, K Picus, J Boyer, M Pitot, HC Rubin, J Philip, PA Nowak, A Wright, JJ Erlichman, C AF Kim, George P. Mahoney, Michelle R. Szydlo, Daniel Mok, Tony S. K. Marshke, Robert Holen, Kyle Picus, Joel Boyer, Michael Pitot, Henry C. Rubin, Joseph Philip, Philip A. Nowak, Anna Wright, John J. Erlichman, Charles TI An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Boronic acids; Antineoplastic agents; Biologic agents; Treatment outcome ID PROTEASOME INHIBITOR PS-341; FACTOR-KAPPA-B; COLORECTAL-CANCER; ACTIVATION; SORAFENIB; MYELOMA; PROTEIN AB Background and Rationale Bortezomib (PS-341, VELCADEA (R)) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitin-proteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. Methods The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. Results Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1-12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. Conclusions This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib. C1 [Kim, George P.] Mayo Clin Florida, Jacksonville, FL USA. [Mahoney, Michelle R.; Szydlo, Daniel; Pitot, Henry C.; Rubin, Joseph; Erlichman, Charles] Mayo Clin Rochester, Rochester, MN USA. [Mok, Tony S. K.] Natl Univ Singapore Hosp, Singapore 117548, Singapore. [Marshke, Robert] Mayo Clin Arizona, Scottsdale, AZ USA. [Holen, Kyle] Univ Wisconsin Carbone Canc Ctr, Madison, WI USA. [Picus, Joel] Washington Univ, St Louis, MO USA. [Boyer, Michael] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. [Philip, Philip A.] Karmanos Canc Inst, Detroit, MI USA. [Nowak, Anna] Sir Charles Gairdner Hosp, Perth, WA, Australia. [Wright, John J.] NCI, Rockville, MD USA. RP Kim, GP (reprint author), Mayo Clin Florida, Jacksonville, FL USA. EM kim.george@mayo.edu RI Nowak, Anna/B-2487-2013 OI Nowak, Anna/0000-0002-9317-9526 FU Phase 2 Consortium [NCI N01 CM17104] FX Supported by the Phase 2 Consortium Contract (NCI N01 CM17104). NR 31 TC 28 Z9 29 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2012 VL 30 IS 1 BP 387 EP 394 DI 10.1007/s10637-010-9532-1 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 876QC UT WOS:000299121500043 PM 20839030 ER PT J AU Veech, RL Valeri, CR VanItallie, TB AF Veech, Richard L. Valeri, C. Robert VanItallie, Theodore B. TI The mitochondrial permeability transition pore provides a key to the diagnosis and treatment of traumatic brain injury SO IUBMB LIFE LA English DT Article DE TBI; ketone bodies; mPTP; cyclosporine A; brain energetics ID CYCLOSPORINE-A; METABOLISM; GLUCOSE; PYROPHOSPHATE; DYSFUNCTION; APOPTOSIS; DAMAGE AB The pathological consequences of traumatic head injury result largely from the opening of the mitochondrial permeability transition pore (mPTP). The mPTP opens due to a decrease in brain phosphorylation energy resulting in a further decrease in brain ATP production and a measurable increase in brain heat generation and temperature. The increase in brain temperature can be measured transcranially by near infrared spectroscopy which can be used to diagnose traumatic brain injury (TBI) and to monitor treatment. Effective therapy of TBI can be achieved by closure of the mPTP by administration of cyclosporine A or by oral administration of ketone body esters. While ketosis has previously been known to prevent damage from TBI, the availability of oral ketone esters presents the first practical modality of achieving therapeutic levels of ketone bodies. (c) 2012 IUBMB Life, 2012 C1 [Veech, Richard L.] NIAAA, Lab Metab Control, NIH, Rockville, MD 20852 USA. [Valeri, C. Robert] Naval Blood Res Lab Inc, Boston, MA USA. [VanItallie, Theodore B.] Columbia Univ, Dept Med, St Lukes Roosevelt Hosp Ctr, Coll Phys & Surg, New York, NY USA. RP Veech, RL (reprint author), NIAAA, Lab Metab Control, NIH, Rockville, MD 20852 USA. EM rveech@mail.nih.gov FU Defense Research Project Administration, DARPA FX Support for development of the ketone ester from the Defense Research Project Administration, DARPA, is gratefully acknowledged. NR 25 TC 10 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD FEB PY 2012 VL 64 IS 2 BP 203 EP 207 DI 10.1002/iub.590 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 875OE UT WOS:000299039800013 PM 22241645 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI Comment Defining Life: An Exercise in Semantics or A Route to Biological Insights? SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Editorial Material ID EVOLUTION C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 11 TC 2 Z9 2 U1 2 U2 10 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 603 EP 605 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 876SN UT WOS:000299128100004 PM 22208253 ER PT J AU Weinberger, DM Simonsen, L Jordan, R Steiner, C Miller, M Viboud, C AF Weinberger, Daniel M. Simonsen, Lone Jordan, Richard Steiner, Claudia Miller, Mark Viboud, Cecile TI Impact of the 2009 Influenza Pandemic on Pneumococcal Pneumonia Hospitalizations in the United States SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID A H1N1 INFECTION; STREPTOCOCCUS-PNEUMONIAE; BACTERIAL PNEUMONIA; DISEASE; VIRUS; ASSOCIATION; CHILDREN; COINFECTIONS; PATHOGENS; EFFICACY AB Background. Infection with influenza virus increases the risk for developing pneumococcal disease. The A/H1N1 influenza pandemic in autumn 2009 provided a unique opportunity to evaluate this relationship. Background. Infection with influenza virus increases the risk for developing pneumococcal disease. The A/H1N1 influenza pandemic in autumn 2009 provided a unique opportunity to evaluate this relationship. Methods. Using weekly age-, state-, and cause-specific hospitalizations from the US State Inpatient Databases of the Healthcare Cost and Utilization Project 2003-2009, we quantified the increase in pneumococcal pneumonia hospitalization rates above a seasonal baseline during the pandemic period. Results. We found a significant increase in pneumococcal hospitalizations from late August to mid-December 2009, which corresponded to the timing of highest pandemic influenza activity. Individuals aged 5-19 years, who have a low baseline level of pneumococcal disease, experienced the largest relative increase in pneumococcal hospitalizations (ratio, 1.6 [95% confidence interval {CI}, 1.4-1.7]), whereas the largest absolute increase was observed among individuals aged 40-64 years. In contrast, there was no excess disease in the elderly. Geographical variation in the timing of excess pneumococcal hospitalizations matched geographical patterns for the fall pandemic influenza wave. Conclusions. The 2009 influenza pandemic had a significant impact on the rate of pneumococcal pneumonia hospitalizations, with the magnitude of this effect varying between age groups and states, mirroring observed variations in influenza activity. C1 [Weinberger, Daniel M.; Simonsen, Lone; Miller, Mark; Viboud, Cecile] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Simonsen, Lone] George Washington Univ, Dept Global Hlth, Washington, DC USA. [Jordan, Richard] Social & Sci Syst Inc, Rockville, MD USA. [Jordan, Richard; Steiner, Claudia] Agcy Healthcare Res & Qual, Healthcare Cost & Utilizat Project, Rockville, MD USA. RP Weinberger, DM (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 16,16 Ctr Dr, Bethesda, MD 20892 USA. EM weinbergerdm@mail.nih.gov OI Simonsen, Lone/0000-0003-1535-8526; Weinberger, Daniel/0000-0003-1178-8086 FU International Influenza Unit, Office of Global Affairs, US Department of Health and Human Services; RAPIDD program (Research And Policy for Infectious Diseases Dynamics); Fogarty International Center, National Institutes of Health (NIH); Department of Homeland Security; Pfizer FX The MISMS study is funded by the International Influenza Unit, Office of Global Affairs, US Department of Health and Human Services. L. S. acknowledges support from the RAPIDD program (Research And Policy for Infectious Diseases Dynamics) funded by the Fogarty International Center, National Institutes of Health (NIH), and the Department of Homeland Security.; L. S. has received research support from Pfizer for an observational study of pneumococcal vaccine program benefits. All other authors report no conflicts. NR 42 TC 39 Z9 42 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2012 VL 205 IS 3 BP 458 EP 465 DI 10.1093/infdis/jir749 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 876HA UT WOS:000299097200015 PM 22158564 ER PT J AU Tobian, AAR Kigozi, G Redd, AD Serwadda, D Kong, XR Oliver, A Nalugoda, F Quinn, TC Gray, RH Wawer, MJ AF Tobian, Aaron A. R. Kigozi, Godfrey Redd, Andrew D. Serwadda, David Kong, Xiangrong Oliver, Amy Nalugoda, Fred Quinn, Thomas C. Gray, Ronald H. Wawer, Maria J. TI Male Circumcision and Herpes Simplex Virus Type 2 Infection in Female Partners: A Randomized Trial in Rakai, Uganda SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-PAPILLOMAVIRUS; HIV PREVENTION; MEN; TRANSMISSION; SYPHILIS AB Male circumcision reduces acquisition of herpes simplex virus type 2 (HSV-2) in men. We assessed whether male circumcision reduces HSV-2 infection among female partners. HSV-2-negative, human immunodeficiency virus-negative female partners of 368 males who were and 372 males who were not randomized to receive male circumcision were enrolled. The incidence of HSV-2 infection among females over a period of 2 years was 6.09 cases per 100 person-years in the intervention arm and 6.32 cases per 100 person-years in the control arm (incidence rate ratio [IRR], 0.96 [95% confidence interval {CI},.62-1.49]; P 5.87). Among female partners of HSV2- positive males, the incidence of HSV-2 infection was 9.55 cases per 100 person-years in the intervention arm and 11.17 cases per 100 person-years in the control arm (IRR, 0.85 [95% CI,.44-1.67]; P 5.62). Contrary to findings in males, male circumcision did not affect HSV-2 acquisition among female partners. C1 [Tobian, Aaron A. R.] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21287 USA. [Oliver, Amy; Quinn, Thomas C.] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21287 USA. [Tobian, Aaron A. R.; Kong, Xiangrong; Gray, Ronald H.; Wawer, Maria J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA. [Kong, Xiangrong] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21287 USA. [Redd, Andrew D.; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Kigozi, Godfrey; Serwadda, David; Nalugoda, Fred; Gray, Ronald H.; Wawer, Maria J.] Rakai Hlth Sci Program, Entebbe, Uganda. [Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. RP Tobian, AAR (reprint author), Johns Hopkins Univ, Dept Pathol, Sch Med, Carnegie 667,600 N Wolfe St, Baltimore, MD 21287 USA. EM atobian1@jhmi.edu FU Bill and Melinda Gates Foundation [22006.02]; National Institutes of Health (NIH) [U1AI51171, 1K23AI093152-01A1]; Doris Duke Charitable Foundation [2011036]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH; Fogarty International Center [5D43TW001508, D43TW00015]; Doris Duke Charitable Foundation; Johns Hopkins University FX The trials were supported by the Bill and Melinda Gates Foundation (22006.02) and the National Institutes of Health (NIH; U1AI51171); this work was supported by the Doris Duke Charitable Foundation (2011036), along with the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, for laboratory support; the Fogarty International Center (5D43TW001508 and D43TW00015), for contributions to training; and the Doris Duke Charitable Foundation, NIH (1K23AI093152-01A1 to A. A. R. T.), and Johns Hopkins University Clinician Scientist Development Award (to A. A. R. T.). NR 15 TC 13 Z9 14 U1 0 U2 1 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 486 EP 490 DI 10.1093/infdis/jir767 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 876HA UT WOS:000299097200018 PM 22147796 ER PT J AU Markt, SC Rodriguez, AC Burk, RD Hildesheim, A Herrero, R Wacholder, S Hutchinson, M Schiffman, M AF Markt, Sarah Coseo Rodriguez, Ana C. Burk, Robert D. Hildesheim, Allan Herrero, Rolando Wacholder, Sholom Hutchinson, Martha Schiffman, Mark TI Longitudinal Analysis of Carcinogenic Human Papillomavirus Infection and Associated Cytologic Abnormalities in the Guanacaste Natural History Study: Looking Ahead to Cotesting SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RISK HUMAN-PAPILLOMAVIRUS; CERVICAL-CANCER; COSTA-RICA; HPV DNA; FOLLOW-UP; WOMEN; CLEARANCE; NEOPLASIA; SMEAR; LOAD AB Background. Few studies have addressed the timing of cervical cytologic abnormalities and human papillomavirus (HPV) positivity during the course of an infection. It remains largely unknown how infections detected by HPV and cytology wax and wane relative to each other. The aim of this analysis was to assess the longitudinal relationship of abnormal cytology and HPV positivity in a 7-year prospective study of 2500 women in Guanacaste, Costa Rica. Methods. At each semiannual or annual visit, cervical specimens were screened using liquid-based cytology and tested for > 40 HPV types with use of MY09/MY11 L1 degenerate primer polymerase chain reaction-based methods. On the basis of previous work, we separated prevalent and newly detected infections in younger and older women. Results. Among newly detected HPV- and/or cytology-positive events, HPV and cytology appeared together similar to 60% of the time; when discordant, HPV tended to appear before cytology in younger and older women. Combining newly and prevalently detected events, HPV and cytology disappeared at the same time > 70% of the time. When discordant, HPV tended to disappear after cytology in younger and older women. Conclusions. Detection of HPV DNA and associated cytological abnormalities tend to come and leave together; however, when discordant, detection of HPV DNA tends to precede and/or last longer than associated cytologic abnormalities. C1 [Markt, Sarah Coseo] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Markt, Sarah Coseo; Hildesheim, Allan; Wacholder, Sholom; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Rodriguez, Ana C.; Herrero, Rolando] Fdn INCIENSA, Liberia, Costa Rica. [Burk, Robert D.] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY USA. [Hutchinson, Martha] Brown Univ, Women & Infants Hosp, Dept Pathol, Providence, RI USA. RP Markt, SC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,9th Floor, Boston, MA 02115 USA. EM scoseo@hsph.harvard.edu RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU National Institutes of Health research training grant (NIH) [R25 CA098566]; National Cancer Institute, NIH, Department of Health and Human Services [NO1-CP-21081, NO1-CP-33061, NO1-CP-40542, NO1-CP-506535] FX This work was supported in part by the National Institutes of Health research training grant (NIH, R25 CA098566 to S. C. M.). The Guanacaste Project was supported by National Cancer Institute, NIH, Department of Health and Human Services (NO1-CP-21081, NO1-CP-33061, NO1-CP-40542, and NO1-CP-506535). NR 25 TC 5 Z9 5 U1 0 U2 1 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 498 EP 505 DI 10.1093/infdis/jir746 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 876HA UT WOS:000299097200020 PM 22147792 ER PT J AU Hallett, M AF Hallett, Mark TI EMG analysis of stereotyped voluntary movements in man SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Editorial Material C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, 10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov NR 7 TC 1 Z9 1 U1 3 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD FEB PY 2012 VL 83 IS 2 BP 122 EP 123 DI 10.1136/jnnp-2011-301283 PG 2 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 877IC UT WOS:000299170100002 PM 22228784 ER PT J AU Liberski, PP Sikorska, B Lindenbaum, S Goldfarb, LG McLean, C Hainfellner, JA Brown, P AF Liberski, Pawel P. Sikorska, Beata Lindenbaum, Shirley Goldfarb, Lev G. McLean, Catriona Hainfellner, Johannes A. Brown, Paul TI Kuru: Genes, Cannibals and Neuropathology SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Review DE Kuru; Prion diseases; Transmissible spongiform encephalopathies ID CREUTZFELDT-JAKOB-DISEASE; PRION PROTEIN; SPONGIFORM ENCEPHALOPATHIES; TRANSMISSION; SCRAPIE; VARIANT; PATHOLOGY; GENOTYPE; BRAIN; CHIMPANZEES AB Kuru was the first human transmissible spongiform encephalopathy (TSE) or prion disease identified, occurring in the Fore linguistic group of Papua New Guinea. Kuru was a uniformly fatal cerebellar ataxic syndrome, usually followed by choreiform and athetoid movements. Kuru imposed a strong balancing selection on the Fore population, with individuals homozygous for the 129 Met allele of the gene (PRNP) encoding for prion protein (PrP) being the most susceptible. The decline in the incidence of kuru in the Fore has been attributed to the exhaustion of the susceptible genotype and ultimately by discontinuation of exposure via cannibalism. Neuropathologically, kuru-affected brains were characterized by widespread degeneration of neurons, astroglial and microglial proliferation, and the presence of amyloid plaques. These early findings have been confirmed and extended by recent immunohistochemical studies for the detection of the TSE-specific PrP (PrPTSE). Confocal laser microscopy also showed the concentration of glial fibrillary acidic protein-positive astrocytic processes at the plaque periphery. The fine structure of plaques corresponds to that described earlier by light microscopy. The successful experimental transmission of kuru led to the awareness of its similarity to Creutzfeldt-Jakob disease and Gerstmann-Straussler-Scheinker disease and formed a background against which the recent epidemics of iatrogenic and variant Creutzfeldt-Jakob disease could be studied. C1 [Liberski, Pawel P.; Sikorska, Beata] Med Univ Lodz, Dept Mol Pathol & Neuropathol, Lodz, Poland. [Lindenbaum, Shirley] CUNY, Grad Ctr, New York, NY USA. [Goldfarb, Lev G.] NINDS, NIH, Bethesda, MD 20892 USA. [McLean, Catriona] Alfred Hosp, Dept Anat Pathol, Melbourne, Vic, Australia. [Hainfellner, Johannes A.] Med Univ Vienna, Inst Neurol, Obersteiner Inst, Vienna, Austria. [Brown, Paul] CEA DSV iMETI SEPIA, Inst Emerging Dis, Fontenay Aux Roses, France. RP Liberski, PP (reprint author), Med Univ Lodz, Dept Mol Pathol & Neuropathol, Lodz, Poland. EM ppliber@csk.umed.lodz.pl FU Austrian Agency for International Cooperation in Education and Research (OeAD) FX Pawel Liberski, Beata Sikorska, and Johannes Hainfellner are supported by the Austrian Agency for International Cooperation in Education and Research (OeAD). NR 89 TC 5 Z9 5 U1 2 U2 59 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD FEB PY 2012 VL 71 IS 2 BP 92 EP 103 DI 10.1097/NEN.0b013e3182444efd PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 879IQ UT WOS:000299323300001 PM 22249461 ER PT J AU Ma, WLD Brenowitz, SD AF Ma, Wei-Li Diana Brenowitz, Stephan D. TI Single-neuron recordings from unanesthetized mouse dorsal cochlear nucleus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE in vivo preparation; extracellular spike; auditory physiology ID COMPLEX-SPIKING NEURONS; PHYSIOLOGICAL-RESPONSE PROPERTIES; LABELED FUSIFORM CELLS; INFERIOR COLLICULUS; SOUND LOCALIZATION; INTRACELLULAR-RECORDINGS; ULTRASONIC VOCALIZATIONS; DECEREBRATE GERBILS; DISCHARGE PATTERNS; ACOUSTIC STRIAE AB Ma WL, Brenowitz SD. Single-neuron recordings from unanesthetized mouse dorsal cochlear nucleus. J Neurophysiol 107: 824-835, 2012. First published November 9, 2011; doi:10.1152/jn.00427.2011.-Because of the availability of disease and genetic models, the mouse has become a valuable species for auditory neuroscience that will facilitate long-term goals of understanding neuronal mechanisms underlying the perception and processing of sounds. The goal of this study was to define the basic sound-evoked response properties of single neurons in the mouse dorsal cochlear nucleus (DCN). Neurons producing complex spikes were distinguished as cartwheel cells (CWCs), and other neurons were classified according to the response map scheme previously developed in DCN. Similar to observations in other rodent species, neurons of the mouse DCN exhibit relatively little sound-driven inhibition. As a result, type III was the most commonly observed response. Our findings are generally consistent with the model of DCN function that has been developed in the cat and the gerbil, suggesting that this in vivo mouse preparation will be a useful tool for future studies of auditory physiology. C1 [Ma, Wei-Li Diana; Brenowitz, Stephan D.] Natl Inst Deafness & Other Commun Disorders, Sect Synapt Transmiss, NIDCD, NIH, Bethesda, MD 20892 USA. RP Brenowitz, SD (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Synapt Transmiss, NIDCD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM brenowitzs@nidcd.nih.gov FU National Institute on Deafness and Other Communication Disorders FX Funding for this research was provided by the National Institute on Deafness and Other Communication Disorders Intramural Research Program. NR 74 TC 5 Z9 5 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2012 VL 107 IS 3 BP 824 EP 835 DI 10.1152/jn.00427.2011 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 879HI UT WOS:000299319900009 PM 22072506 ER PT J AU Jacoby, J Kreitzer, MA Alford, S Qian, HH Tchernookova, BK Naylor, ER Malchow, RP AF Jacoby, Jason Kreitzer, Matthew A. Alford, Simon Qian, Haohua Tchernookova, Boriana K. Naylor, Ethan R. Malchow, Robert Paul TI Extracellular pH dynamics of retinal horizontal cells examined using electrochemical and fluorometric methods SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE retina; feedback; lateral inhibition ID CONE PHOTORECEPTORS; CALCIUM CURRENTS; LIGHT RESPONSES; PRIMATE RETINA; FEEDBACK; INHIBITION; CATFISH; MODULATION; LANTHANUM; ATPASE AB Jacoby J, Kreitzer MA, Alford S, Qian H, Tchernookova BK, Naylor ER, Malchow RP. Extracellular pH dynamics of retinal horizontal cells examined using electrochemical and fluorometric methods. J Neurophysiol 107: 868-879, 2012. First published November 16, 2011; doi:10.1152/jn.00878.2011.-Extracellular H+ has been hypothesized to mediate feedback inhibition from horizontal cells onto vertebrate photoreceptors. According to this hypothesis, depolarization of horizontal cells should induce extracellular acidification adjacent to the cell membrane. Experiments testing this hypothesis have produced conflicting results. Studies examining carp and goldfish horizontal cells loaded with the pH-sensitive dye 5-hexadecanoylaminofluorescein (HAF) reported an extracellular acidification on depolarization by glutamate or potassium. However, investigations using H+-selective microelectrodes report an extracellular alkalinization on depolarization of skate and catfish horizontal cells. These studies differed in the species and extracellular pH buffer used and the presence or absence of cobalt. We used both techniques to examine H+ changes from isolated catfish horizontal cells under identical experimental conditions (1 mM HEPES, no cobalt). HAF fluorescence indicated an acidification response to high extracellular potassium or glutamate. However, a clear extracellular alkalinization was found using H+-selective microelectrodes under the same conditions. Confocal microscopy revealed that HAF was not localized exclusively to the extracellular surface, but rather was detected throughout the intracellular compartment. A high degree of colocalization between HAF and the mitochondrion-specific dye MitoTracker was observed. When HAF fluorescence was monitored from optical sections from the center of a cell, glutamate produced an intracellular acidification. These results are consistent with a model in which depolarization allows calcium influx, followed by activation of a Ca2+/H+ plasma membrane ATPase. Our results suggest that HAF is reporting intracellular pH changes and that depolarization of horizontal cells induces an extracellular alkalinization, which may relieve H+-mediated inhibition of photoreceptor synaptic transmission. C1 [Jacoby, Jason; Alford, Simon; Qian, Haohua; Tchernookova, Boriana K.; Malchow, Robert Paul] Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA. [Kreitzer, Matthew A.; Naylor, Ethan R.] Indiana Wesleyan Univ, Dept Biol, Marion, IN USA. [Qian, Haohua] NEI, Bethesda, MD 20892 USA. [Malchow, Robert Paul] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60607 USA. RP Malchow, RP (reprint author), Univ Illinois, Dept Biol Sci, MC 067,Rm 4083 SEL,840 W Taylor St, Chicago, IL 60607 USA. EM paulmalc@uic.edu FU National Science Foundation [0924372, 0924383, 1005378]; National Eye Institute (University ofIllinois at Chicago) [EY01792]; Marine Biological Laboratory; Midwest Eye-Banks FX This work was supported by National Science Foundation Grants 0924372, 0924383, and 1005378; National Eye Institute Grant EY01792 (University of Illinois at Chicago); a Laura and Arthur Colwin Summer Fellowship from the Marine Biological Laboratory; and the Midwest Eye-Banks. NR 42 TC 11 Z9 11 U1 0 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2012 VL 107 IS 3 BP 868 EP 879 DI 10.1152/jn.00878.2011 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 879HI UT WOS:000299319900013 PM 22090459 ER PT J AU Darbari, DS Onyekwere, O Nouraie, M Minniti, CP Luchtman-Jones, L Rana, S Sable, C Ensing, G Dham, N Campbell, A Arteta, M Gladwin, MT Castro, O Taylor, JG Kato, GJ Gordeuk, V AF Darbari, Deepika S. Onyekwere, Onyinye Nouraie, Mehdi Minniti, Caterina P. Luchtman-Jones, Lori Rana, Sohail Sable, Craig Ensing, Gregory Dham, Niti Campbell, Andrew Arteta, Manuel Gladwin, Mark T. Castro, Oswaldo Taylor, James G. Kato, Gregory J. Gordeuk, Victor TI Markers of Severe Vaso-Occlusive Painful Episode Frequency in Children and Adolescents with Sickle Cell Anemia SO JOURNAL OF PEDIATRICS LA English DT Article ID ACUTE CHEST SYNDROME; ALPHA-THALASSEMIA; ADVERSE OUTCOMES; RISK-FACTORS; DISEASE; CRISES; HYDROXYUREA; HEMOLYSIS; COHORT; HOSPITALIZATION AB Objective To identify factors associated with frequent severe vaso-occlusive pain crises in a contemporary pediatric cohort of patients with sickle cell anemia (SCA) enrolled in a prospective study of pulmonary hypertension and the hypoxic response in sickle cell disease. Study design Clinical and laboratory characteristics of children with SCA who had >= 3 severe pain crises requiring health care in the preceding year were compared with those of subjects with <3 such episodes. Results Seventy-five children (20%) reported >= 3 severe pain episodes in the preceding year, and 232 (61%) had none. Frequent pain episodes were associated with older age (OR, 1.2; 95% CI, 1.1-1.3; P < .0001), alpha-thalassemia trait (OR 3.5; 1.6-6.7; P = .002), higher median hemoglobin (OR 1.7; 95% CI: 1.2-2.4; P < .003), and lower lactate dehydrogenase concentration (OR 1.82; 95% CI: 1.07-3.11; P = .027). Children with high pain frequency also had an increased iron burden (serum ferritin, 480 vs 198 mu g/L; P = .006) and higher median tricuspid regurgitation jet velocity (2.41 vs 2.31 m/s; P = .001). Neither hydroxyurea use nor fetal hemoglobin levels were significantly different according to severe pain history. Conclusions In our cohort of children with SCA, increasing age was associated with higher frequency of severe pain episodes as were a-thalassemia, iron overload, higher hemoglobin and lower lactate dehydrogenase concentration, and higher tricuspid regurgitation velocity. (J Pediatr 2012; 160: 286-90). C1 [Darbari, Deepika S.; Minniti, Caterina P.; Taylor, James G.; Kato, Gregory J.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Onyekwere, Onyinye; Nouraie, Mehdi; Castro, Oswaldo; Gordeuk, Victor] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Darbari, Deepika S.; Luchtman-Jones, Lori] Div Pediat Hematol, Washington, DC USA. [Darbari, Deepika S.; Luchtman-Jones, Lori] Div Oncol, Washington, DC USA. [Rana, Sohail; Dham, Niti] Childrens Natl Med Ctr, Washington, DC 20010 USA. Howard Univ Hosp, Dept Pediat, Washington, DC USA. [Sable, Craig] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Ensing, Gregory] Univ Michigan, Div Pediat Hematol, Ann Arbor, MI 48109 USA. [Campbell, Andrew] Univ Michigan, Div Pediat Pulmonol, Ann Arbor, MI 48109 USA. [Arteta, Manuel] Univ Michigan, Div Pediat Cardiol, Ann Arbor, MI 48109 USA. [Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Darbari, DS (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014; OI Kato, Gregory/0000-0003-4465-3217; Taylor, James/0000-0002-4421-1809 FU National Heart, Lung, and Blood Institute [2-R25 HL003679, 1-R01 HL079912]; Howard University General Clinic Research Center; National Center for Research Resources [2MOI RR10284-10]; National Institutes of Health, Bethesda, MD; National Institutes of Health FX Supported in part by National Heart, Lung, and Blood Institute (grants 2-R25 HL003679 and 1-R01 HL079912), Howard University General Clinic Research Center, National Center for Research Resources (grant 2MOI RR10284-10), National Institutes of Health, Bethesda, MD, and the Intramural Research Program of the National Institutes of Health. The authors declare no conflicts of interest. NR 30 TC 24 Z9 26 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD FEB PY 2012 VL 160 IS 2 BP 286 EP 290 DI 10.1016/j.jpeds.2011.07.018 PG 5 WC Pediatrics SC Pediatrics GA 876MU UT WOS:000299112400026 PM 21890147 ER PT J AU Borghese, CM Blednov, YA Quan, Y Iyer, SV Xiong, W Mihic, SJ Zhang, L Lovinger, DM Trudell, JR Homanics, GE Harris, RA AF Borghese, Cecilia M. Blednov, Yuri A. Quan, Yu Iyer, Sangeetha V. Xiong, Wei Mihic, S. John Zhang, Li Lovinger, David M. Trudell, James R. Homanics, Gregg E. Harris, R. Adron TI Characterization of Two Mutations, M287L and Q266I, in the alpha 1 Glycine Receptor Subunit That Modify Sensitivity to Alcohols SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GATED ION-CHANNEL; FRAMESHIFT MUTATION; CHLORIDE CURRENTS; SINGLE-CHANNEL; HYPEREKPLEXIA; MICE; ETHANOL; MUTANT; GABA(A); RESPONSES AB Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels. Ethanol potentiates glycine activation of the GlyR, and putative binding sites for alcohol are located in the transmembrane (TM) domains between and within subunits. To alter alcohol sensitivity of GlyR, we introduced two mutations in the GlyR alpha 1 subunit, M287L (TM3) and Q266I (TM2). After expression in Xenopus laevis oocytes, both mutants showed a reduction in glycine sensitivity and glycine-induced maximal currents. Activation by taurine, another endogenous agonist, was almost abolished in the M287L GlyR. The ethanol potentiation of glycine currents was reduced in the M287L GlyR and eliminated in Q266I. Physiological levels of zinc (100 nM) potentiate glycine responses in wild-type GlyR and also enhance the ethanol potentiation of glycine responses. Although zinc potentiation of glycine responses was unchanged in both mutants, zinc enhancement of ethanol potentiation of glycine responses was absent in M287L GlyRs. The Q266I mutation decreased conductance but increased mean open time (effects not seen in M287L). Two lines of knockin mice bearing these mutations were developed. Survival of homozygous knockin mice was impaired, probably as a consequence of impaired glycinergic transmission. Glycine showed a decreased capacity for displacing strychnine binding in heterozygous knockin mice. Electrophysiology in isolated neurons of brain stem showed decreased glycine-mediated currents and decreased ethanol potentiation in homozygous knockin mice. Molecular models of the wildtype and mutant GlyRs show a smaller water-filled cavity within the TM domains of the Q266I alpha 1 subunit. The behavioral characterization of these knockin mice is presented in a companion article (J Pharmacol Exp Ther 340:317-329, 2012). C1 [Borghese, Cecilia M.; Blednov, Yuri A.; Quan, Yu; Iyer, Sangeetha V.; Harris, R. Adron] Univ Texas Austin, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA. [Iyer, Sangeetha V.] Univ Pittsburgh, Grad Program Mol Pharmacol, Pittsburgh, PA USA. [Homanics, Gregg E.] Univ Pittsburgh, Dept Anesthesiol & Pharmacol, Pittsburgh, PA USA. [Homanics, Gregg E.] Univ Pittsburgh, Dept Biol Chem, Pittsburgh, PA USA. [Xiong, Wei; Zhang, Li; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. [Trudell, James R.] Stanford Univ, Dept Anesthesia, Stanford, CA 94305 USA. [Trudell, James R.] Stanford Univ, Beckman Program Mol & Genet Med, Stanford, CA 94305 USA. RP Harris, RA (reprint author), Univ Texas Austin, Waggoner Ctr Alcohol & Addict Res, 1 Univ Stn,A4800, Austin, TX 78712 USA. EM harris@mail.utexas.edu FU National Institutes of Health National Institute of Alcohol Abuse and Alcoholism [AA06399, AA11525, AA10422]; National Institutes of Health National Institute of General Medical Sciences [GM47818] FX This work was supported by the National Institutes of Health National Institute of Alcohol Abuse and Alcoholism [Grants AA06399, AA11525, AA10422]; and the National Institutes of Health National Institute of General Medical Sciences [Grant GM47818]. NR 42 TC 16 Z9 16 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2012 VL 340 IS 2 BP 304 EP 316 DI 10.1124/jpet.111.185116 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 879IT UT WOS:000299323600009 PM 22037201 ER PT J AU Mobley, CC Stadler, DD Staten, MA El Ghormli, L Gillis, B Hartstein, J Siega-Riz, AM Virus, A AF Mobley, Connie C. Stadler, Diane D. Staten, Myrlene A. El Ghormli, Laure Gillis, Bonnie Hartstein, Jill Siega-Riz, Anna Maria Virus, Amy CA HEALTHY Study Grp TI Effect of Nutrition Changes on Foods Selected by Students in a Middle School-Based Diabetes Prevention Intervention Program: The HEALTHY Experience SO JOURNAL OF SCHOOL HEALTH LA English DT Article DE school food services; nutrition and diet; child and adolescent health ID US PUBLIC-SCHOOLS; NUTRIENT CONTENT; ENVIRONMENTS; RATIONALE; COMPONENT; DESIGN; CHILDREN; LUNCHES AB BACKGOUND: The HEALTHY primary prevention trial developed an integrated multicomponent intervention program to moderate risk factors for type 2 diabetes in middle schools. The nutrition component aimed to improve the quality of foods and beverages served to students. Changes in the School Breakfast Program (SBP), National School Lunch Program (NSLP), and a la carte venues are compared to the experience of control schools. METHODS: The intervention was implemented in 21 middle schools from winter 2007 through spring 2009 (following a cohort of students from sixth through eighth grades); 21 schools acted as observed controls. The nutrition component targeted school food service environmental change. Data identifying foods and nutrients served (selected by students for consumption) were collected over a 20-day period at baseline and end of study. Analysis compared end of study values for intervention versus control schools. RESULTS: Intervention schools more successfully limited dessert and snack food portion size in NSLP and a la carte and lowered fat content of foods served. Servings of high-fiber grain-based foods and/ or legumes were improved in SBP but not NSLP. Intervention and control schools eliminated > 1% fat milk and added-sugar beverages in SBP, but intervention schools were more successful in NSLP and a la carte. CONCLUSION: The HEALTHY program demonstrated significant changes in the nutritional quality of foods and beverages served in the SBP, NSLP, and a la carte venues, as part of an effort to decrease childhood obesity and support beneficial effects in some secondary HEALTHY study outcomes. C1 [Mobley, Connie C.] Univ Nevada, Las Vegas, NV 89106 USA. [Stadler, Diane D.] Oregon Hlth & Sci Univ, Div Hlth Promot & Sports Med, Portland, OR 97239 USA. [Stadler, Diane D.] Oregon Hlth & Sci Univ, Grad Programs Human Nutr, Portland, OR 97239 USA. [Staten, Myrlene A.] NIDDK, NIH, Bethesda, MD 20892 USA. [El Ghormli, Laure] George Washington Univ, Biostat Ctr, Rockville, MD 20852 USA. [Gillis, Bonnie] Univ Pittsburgh, Med Ctr Hlth Plan, Hlth Promot Dept, Pittsburgh, PA 15219 USA. [Hartstein, Jill] Univ Calif Irvine, Irvine, CA 92697 USA. [Siega-Riz, Anna Maria] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Virus, Amy] Temple Univ, Ctr Obes Res & Educ, Philadelphia, PA 19140 USA. RP Mobley, CC (reprint author), Univ Nevada, 1001 Shadow Lane,MS 7425, Las Vegas, NV 89106 USA. EM connie.mobley@unlv.edu; stadlerd@ohsu.edu; statenm@niddk.nih.gov; elghorml@biostat.bsc.gwu.edu; gillisbp@upmc.edu; hartstej@uci.edu; am_siegariz@unc.edu; amyvir@temple.edu OI Stadler, Diane/0000-0002-4718-2054 NR 26 TC 13 Z9 13 U1 2 U2 24 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD FEB PY 2012 VL 82 IS 2 BP 82 EP 90 DI 10.1111/j.1746-1561.2011.00670.x PG 9 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA 875PO UT WOS:000299044200004 ER PT J AU Pastrana, DV Wieland, U Silling, S Buck, CB Pfister, H AF Pastrana, Diana V. Wieland, Ulrike Silling, Steffi Buck, Christopher B. Pfister, Herbert TI Positive correlation between Merkel cell polyomavirus viral load and capsid-specific antibody titer SO MEDICAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE MCV; MCPyV; Merkel cell polyomavirus; Neutralization; Viral load; Skin ID BK-VIRUS; JC-VIRUS; DNA-SEQUENCES; HUMAN-TISSUES; INFECTION; CARCINOMA; TRANSMISSION; INDIVIDUALS; PERSISTENCE; EXCRETION AB Merkel cell polyomavirus (MCPyV or MCV) is the first polyomavirus to be clearly implicated as a causal agent underlying a human cancer, Merkel cell carcinoma (MCC). Infection with MCPyV is common in the general population, and a majority of adults shed MCPyV from the surface of their skin. In this study, we quantitated MCPyV DNA in skin swab specimens from healthy volunteers sampled at different anatomical sites over time periods ranging from 3 months to 4 years. The volunteers were also tested using a serological assay that detects antibodies specific for the MCPyV virion. There was a positive correlation between MCPyV virion-specific antibody titers and viral load at all anatomical sites tested (dorsal portion of the hands, forehead, and buttocks) (Spearman's r 0.644, P < 0.0001). The study results are consistent with previous findings suggesting that the skin is primary site of chronic MCPyV infection in healthy adults and suggest that the magnitude of an individual's seroresponsiveness against the MCPyV virion generally reflects the overall MCPyV DNA load across wide areas of the skin. In light of previous reports indicating a correlation between MCC and strong MCPyV-specific seroresponsiveness, this model suggests that poorly controlled chronic MCPyV infection might be a risk factor in the development of MCC. C1 [Pastrana, Diana V.; Buck, Christopher B.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. [Wieland, Ulrike; Silling, Steffi; Pfister, Herbert] Univ Cologne, Inst Virol, Natl Reference Ctr Papilloma & Polyomaviruses, D-50935 Cologne, Germany. RP Buck, CB (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 37,Room 4118,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Ulrike.Wieland@uni-koeln.de; BuckC@mail.nih.gov OI Buck, Christopher/0000-0003-3165-8094 FU NIH; Center for Cancer Research; NCI; German National Reference Center for Papilloma- and Polyomaviruses (German Federal Ministry of Health) [FKZ 1369-401] FX This work was funded in part by the Intramural Research Program of the NIH, with support from the Center for Cancer Research and the NCI Director's Intramural Innovation Award Program, and in part by the German National Reference Center for Papilloma- and Polyomaviruses (German Federal Ministry of Health, grant number FKZ 1369-401). NR 28 TC 18 Z9 18 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0300-8584 J9 MED MICROBIOL IMMUN JI Med. Microbiol. Immunol. PD FEB PY 2012 VL 201 IS 1 BP 17 EP 23 DI 10.1007/s00430-011-0200-7 PG 7 WC Immunology; Microbiology SC Immunology; Microbiology GA 876RN UT WOS:000299125500003 PM 21614514 ER PT J AU Thompson, J Pikis, A AF Thompson, J. Pikis, A. TI Metabolism of sugars by genetically diverse species of oral Leptotrichia SO MOLECULAR ORAL MICROBIOLOGY LA English DT Article DE dental caries; glycosyl hydrolase family 4; Leptotrichia; oral microbiology; phospho-a-glucosidase; sucrose isomers ID PHOSPHO-ALPHA-GLUCOSIDASE; GLUCOSYL-D-FRUCTOSES; STREPTOCOCCUS-MUTANS; BACILLUS-SUBTILIS; FUSOBACTERIUM-MORTIFERUM; KLEBSIELLA-PNEUMONIAE; SUCROSE ISOMERS; ACID PRODUCTION; DENTAL-CARIES; BUCCALIS AB Leptotrichia buccalis ATCC 14201 is a gram-negative, anaerobic rod-shaped bacterium resident in oral biofilm at the tooth surface. The sequenced genome of this organism reveals three contiguous genes at loci: Lebu_1525, Lebu_1526 and Lebu_1527. The translation products of these genes exhibit significant homology with phospho-a-glucosidase (Pagl), a regulatory protein (GntR) and a phosphoenol pyruvate-dependent sugar transport protein (EIICB), respectively. In non-oral bacterial species, these genes comprise the sim operon that facilitates sucrose isomer metabolism. Growth studies showed that L.buccalis fermented a wide variety of carbohydrates, including four of the five isomers of sucrose. Growth on the isomeric disaccharides elicited expression of a 50-kDa polypeptide comparable in size to that encoded by Lebu_1525. The latter gene was cloned, and the expressed protein was purified to homogeneity from Escherichia coli TOP10 cells. In the presence of two cofactors, NAD+ and Mn2+ ions, the enzyme readily hydrolyzed p-nitrophenyl-a-glucopyranoside 6-phosphate (pNPaG6P), a chromogenic analogue of the phosphorylated isomers of sucrose. By comparative sequence alignment, immunoreactivity and signature motifs, the enzyme can be assigned to the phospho-a-glucosidase (Pagl) clade of Family 4 of the glycosyl hydrolase super family. We suggest that the products of Lebu_1527 and Lebu_1525, catalyze the phosphorylative translocation and hydrolysis of sucrose isomers in L.buccalis, respectively. Four genetically diverse, but 16S rDNA-related, species of Leptotrichia have recently been described: L.goodfellowii, L.hofstadii, L.shahii and L.wadei. The phenotypic traits of these new species, with respect to carbohydrate utilization, have also been determined. C1 [Thompson, J.; Pikis, A.] NIDCR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. [Pikis, A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Thompson, J (reprint author), NIDCR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 325,Convent Dr,MSC-4350, Bethesda, MD 20892 USA. EM jthompson@dir.nidcr.nih.gov FU NIDCR, National Institutes of Health, Bethesda, MD FX We thank Rick Dreyfuss for assistance with photography and computer graphics and Nga Nguyen for microsequence analyses. This work was supported by the Intramural Research Program of the NIDCR, National Institutes of Health, Bethesda, MD. NR 42 TC 2 Z9 5 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2041-1006 J9 MOL ORAL MICROBIOL JI Mol. Oral Microbiol. PD FEB PY 2012 VL 27 IS 1 BP 34 EP 44 DI 10.1111/j.2041-1014.2011.00627.x PG 11 WC Dentistry, Oral Surgery & Medicine; Microbiology SC Dentistry, Oral Surgery & Medicine; Microbiology GA 874II UT WOS:000298948900004 PM 22230464 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 Barber, DL Andrade, BB Sereti, I Sher, A AF Barber, Daniel L. Andrade, Bruno B. Sereti, Irini Sher, Alan TI Immune reconstitution inflammatory syndrome: the trouble with immunity when you had none SO NATURE REVIEWS MICROBIOLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HIV-INFECTED PATIENTS; PNEUMOCYSTIS-CARINII-PNEUMONIA; ORGAN TRANSPLANT RECIPIENTS; CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY; RISK-FACTORS; RESTORATION DISEASE; MYCOBACTERIUM-TUBERCULOSIS; HOMEOSTATIC PROLIFERATION AB Some individuals who are infected with HIV rapidly deteriorate shortly after starting antiretroviral therapy, despite effective viral suppression. This reaction, referred to as immune reconstitution inflammatory syndrome ( IRIS), is characterized by tissue-destructive inflammation and arises as CD4(+) T cells re-emerge. It has been proposed that IRIS is caused by a dysregulation of the expanding population of CD4(+) T cells specific for a co-infecting opportunistic pathogen. Here, we argue that IRIS instead results from hyper-responsiveness of the innate immune system to T cell help, a mechanism that may be shared by the many manifestations of IRIS that occur following the reversal of other types of immunosuppression in pathogen-infected hosts. C1 [Barber, Daniel L.; Andrade, Bruno B.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Sereti, Irini] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Barber, DL (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Rm 6146,50 South Dr, Bethesda, MD 20892 USA. EM barberd@niaid.nih.gov RI Andrade, Bruno/J-9111-2012 OI Andrade, Bruno/0000-0001-6833-3811 FU US National Institute for Allergy and Infectious Diseases, National Institutes of Health FX The authors thank J. Keane for stimulating discussions during the preparation of this article. Work in the authors' laboratories is supported by the intramural research programme of the US National Institute for Allergy and Infectious Diseases, National Institutes of Health. NR 71 TC 58 Z9 60 U1 1 U2 6 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 150 EP 156 DI 10.1038/nrmicro2712 PG 7 WC Microbiology SC Microbiology GA 876NS UT WOS:000299115000014 PM 22230950 ER PT J AU Rahimi, Z Vaisi-Raygani, A Rahimi, Z Parsian, A AF Rahimi, Zohreh Vaisi-Raygani, Asad Rahimi, Ziba Parsian, Abbas TI Concomitant presence of endothelial nitric oxide 894T and angiotensin II-converting enzyme D alleles are associated with diabetic nephropathy in a Kurdish population from Western Iran SO NEPHROLOGY LA English DT Article DE ACE I; D; eNOS G894T; macroalbuminuria; microalbuminuria; type 2 diabetes mellitus ID STAGE RENAL-DISEASE; ENOS GLU298ASP POLYMORPHISM; SYNTHASE GENE; INSERTION/DELETION POLYMORPHISM; ACE GENE; TYPE-2; HYPERTENSION; RISK; CLEAVAGE; VARIANT AB Aim: The present study investigated the influence of insertion (I)/deletion (D) polymorphism of the angiotensin II-converting enzyme (ACE) gene in combination with endothelial nitric oxide (eNOS) G894T polymorphism on the predisposition to diabetic nephropathy (DN). Methods: Using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) method, the ACE and eNOS polymorphisms were genotyped in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric type 2 diabetes mellitus (T2DM) patients from Western Iran. Results: The presence of eNOS T or ACE D allele was not associated with increased risk of macroalbuminuria (odds ratio (OR) = 1.36, P = 0.27 and OR = 1.6, P = 0.062, respectively). However, in the presence of both alleles there was a trend towards increased risk of macroalbuminuria (fivefold, P = 0.05). Conclusion: Our study indicates that the concomitant presence of both ACE D and eNOS T alleles tends to be associated with an elevation risk of macroalbuminuria compared with the presence of each polymorphism alone. This risk could be attributed to the increasing activity of ACE and angiotensin II level in the presence of D allele and decreasing NO production in the presence of T allele accelerating diabetic nephropathy. C1 [Rahimi, Zohreh; Rahimi, Ziba] Kermanshah Univ Med Sci, Med Biol Res Ctr, Sch Med, Kermanshah, Iran. [Rahimi, Zohreh; Vaisi-Raygani, Asad] Kermanshah Univ Med Sci, Dept Biochem, Sch Med, Kermanshah, Iran. [Parsian, Abbas] NIAAA, Div Neurosci & Behav, NIH, Rockville, MD 20852 USA. RP Rahimi, Z (reprint author), Kermanshah Univ Med Sci, Med Biol Res Ctr, Sch Med, POB 67148-69914,Daneshgah Ave, Kermanshah, Iran. EM zrahimi@kums.ac.ir; zrahimi@kums.ac.ir OI Rahimi, Zohreh/0000-0001-7589-3307; Vaisi-Raygani, Asad/0000-0002-3042-2832 FU Kermanshah University of Medical Sciences, Kermanshah, Iran FX This work was financially supported by a grant from Vice Chancellor for Research of Kermanshah University of Medical Sciences, Kermanshah, Iran. NR 35 TC 12 Z9 12 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD FEB PY 2012 VL 17 IS 2 BP 175 EP 181 DI 10.1111/j.1440-1797.2011.01533.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 878JH UT WOS:000299252400010 PM 22026967 ER PT J AU Yan, YJ Pushparaj, A Le Strat, Y Gamaleddin, I Barnes, C Justinova, Z Goldberg, SR Le Foll, B AF Yan, Yijin Pushparaj, Abhiram Le Strat, Yann Gamaleddin, Islam Barnes, Chanel Justinova, Zuzana Goldberg, Steven R. Le Foll, Bernard TI Blockade of Dopamine D4 Receptors Attenuates Reinstatement of Extinguished Nicotine-Seeking Behavior in Rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE dopamine receptor D4; receptor antagonist; nicotine self-administration; reinstatement of nicotine-seeking behavior; tobacco smoking; relapse ID DRD4 VNTR POLYMORPHISM; CUE-INDUCED REINSTATEMENT; NUCLEUS-ACCUMBENS SHELL; D-4 RECEPTOR; MENTAL-HEALTH; SMOKING CUES; D4 RECEPTORS; TOBACCO USE; COCAINE DISCRIMINATION; PSYCHIATRIC-DISORDERS AB Since cloning of the dopamine receptor D4 (DRD4), its role in the brain has remained unclear. It has been reported that polymorphism of the DRD4 gene in humans is associated with reactivity to cues related to tobacco smoking. However, the role of DRD4 in animal models of nicotine addiction has seldom been explored. In our study, male Long-Evans rats learned to intravenously self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Effects of the selective DRD4 antagonist L-745,870 were evaluated on nicotine self-administration behavior and on reinstatement of extinguished nicotine-seeking behavior induced by nicotine-associated cues or by priming injections of nicotine. L-745,870 was also tested on reinstatement of extinguished food-seeking behavior as a control. In addition, the selective DRD4 agonist PD 168,077 was tested for its ability to reinstate extinguished nicotine-seeking behavior. Finally, L-745,870 was tested in Sprague Dawley rats trained to discriminate administration of 0.4 mg/kg nicotine from vehicle under an FR schedule of food delivery. L-745,870 significantly attenuated reinstatement of nicotine-seeking induced by both nicotine-associated cues and nicotine priming. In contrast, L-745,870 did not affect established nicotine self-administration behavior or reinstatement of food-seeking behavior induced by food cues or food priming. L-745,870 did not produce nicotine-like discriminative-stimulus effects and did not alter discriminative-stimulus effects of nicotine. PD 168,077 did not reinstate extinguished nicotine-seeking behavior. As DRD4 blockade by L-745,870 selectively attenuated both cue-and nicotine-induced reinstatement of nicotine-seeking behavior, without affecting cue-or food-induced reinstatement of food-seeking behavior, DRD4 antagonists are potential therapeutic agents against tobacco smoking relapse. Neuropsychopharmacology (2012) 37, 685-696; doi: 10.1038/npp.2011.245; published online 26 October 2011 C1 [Yan, Yijin; Pushparaj, Abhiram; Le Strat, Yann; Gamaleddin, Islam; Le Foll, Bernard] Univ Toronto, Translat Addict Res Lab, Ctr Addict & Mental Hlth Addict CAMH, Toronto, ON M5S 2S1, Canada. [Barnes, Chanel; Justinova, Zuzana; Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,US Dept HHS, Baltimore, MD USA. [Justinova, Zuzana] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA. [Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada. RP Le Foll, B (reprint author), Univ Toronto, Translat Addict Res Lab, Ctr Addict & Mental Hlth Addict CAMH, 33 Russell St, Toronto, ON M5S 2S1, Canada. EM bernard_lefoll@camh.net RI Yan, Yijin/C-2733-2012; Justinova, Zuzana/A-9109-2011; Le Foll, Bernard/K-2952-2014; OI Justinova, Zuzana/0000-0001-5793-7484; Le Foll, Bernard/0000-0002-6406-4973; Pushparaj, Abhiram/0000-0002-7109-9795 FU Canadian Tobacco Control Research Initiate (CTCRI) [20040]; Canadian Institute of Health Research (CIHR) [200810MFE-193820-172560]; National Institute on Drug Abuse FX We thank Drs John Roder and Benoit Forget for their comments on our experimental data. This study was supported partly by the Canadian Tobacco Control Research Initiate (CTCRI) Student Research Grant (no. 20040), by the Canadian Institute of Health Research (CIHR) postdoctoral fellowship (Code No. 200810MFE-193820-172560), by the CIHR Strategic Training Program in Tobacco Use in Special Populations (TUSP) postdoctoral fellowship and in part by the Intramural Research Program of the National Institute on Drug Abuse. NR 97 TC 30 Z9 30 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2012 VL 37 IS 3 BP 685 EP 696 DI 10.1038/npp.2011.245 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 876OV UT WOS:000299117900011 PM 22030716 ER PT J AU Weyerbrock, A Osterberg, N Psarras, N Baumer, B Kogias, E Werres, A Bette, S Saavedra, JE Keefer, LK Papazoglou, A AF Weyerbrock, Astrid Osterberg, Nadja Psarras, Nikolaos Baumer, Brunhilde Kogias, Evangelos Werres, Anna Bette, Stefanie Saavedra, Joseph E. Keefer, Larry K. Papazoglou, Anna TI JS-K, a Glutathione S-Transferase-Activated Nitric Oxide Donor With Antineoplastic Activity in Malignant Gliomas SO NEUROSURGERY LA English DT Article DE Glioma; GST; JS-K; Nitric oxide (NO); U87 ID CELLS IN-VITRO; SOLUBLE GUANYLYL CYCLASE; MYELOID-LEUKEMIA CELLS; CYTOCHROME-C RELEASE; FACTOR-KAPPA-B; CASPASE ACTIVATION; TUMOR PROGRESSION; DRUG-RESISTANCE; KINASE PATHWAYS; BRAIN-TUMORS AB BACKGROUND: Glutathione S-transferases (GSTs) control multidrug resistance and are upregulated in many cancers, including malignant gliomas. The diazeniumdiolate JS-K generates nitric oxide (NO) on enzymatic activation by glutathione and GST, showing promising NO-based anticancer efficacy. OBJECTIVE: To evaluate the role of NO-based antitumor therapy with JS-K in U87 gliomas in vitro and in vivo. METHODS: U87 glioma cells and primary glioblastoma cell lines were exposed to JS-K and a variety of inhibitors to study cell death by necrosis, apoptosis, and other mechanisms. GST expression was evaluated by immunocytochemistry, polymerase chain reaction, and Western blot, and NO release from JS-K was studied with a NO assay. The growth-inhibitory effect of JS-K was studied in a U87 xenograft model in vivo. RESULTS: Dose-dependent inhibition of cell proliferation was observed in human U87 glioma cells and primary glioblastoma cells in vitro. Cell death was partially induced by caspase-dependent apoptosis, which could be blocked by Z-VAD-FMK and Q-VD-OPH. Inhibition of GST by sulfasalazine, cGMP inhibition by ODQ, and MEK1/2 inhibition by UO126 attenuated the antiproliferative effect of JS-K, suggesting the involvement of various intracellular death signaling pathways. Response to JS-K correlated with mRNA and protein expression of GST and the amount of NO released by the glioma cells. Growth of U87 xenografts was reduced significantly, with immunohistochemical evidence for increased necrosis and apoptosis and reduced proliferation. CONCLUSION: Our data show for the first time the potent antiproliferative effect of JS-K in gliomas in vitro and in vivo. These findings warrant further investigation of this novel NO-releasing prodrug in gliomas. C1 [Weyerbrock, Astrid; Osterberg, Nadja; Psarras, Nikolaos; Baumer, Brunhilde; Kogias, Evangelos; Werres, Anna; Bette, Stefanie] Univ Med Ctr Freiburg, Dept Neurosurg, D-79106 Freiburg, Germany. [Saavedra, Joseph E.] NCI, SAIC Frederick, Frederick, MD 21701 USA. [Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. [Papazoglou, Anna] Univ Med Ctr Freiburg, Dept Stereotact Neurosurg, D-79106 Freiburg, Germany. RP Weyerbrock, A (reprint author), Univ Med Ctr Freiburg, Dept Neurosurg, Breisacher Str 64, D-79106 Freiburg, Germany. EM astrid.weyerbrock@uniklinik-freiburg.de RI Weyerbrock, Astrid/E-8493-2014; Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research (Dr Saavedra) and by federal funds from the National Cancer Institute, National Institutes of Health under contract HHSN261200800001E. The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article. NR 56 TC 13 Z9 16 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD FEB PY 2012 VL 70 IS 2 BP 497 EP 510 DI 10.1227/NEU.0b013e31823209cf PG 14 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 879IK UT WOS:000299322700066 PM 21849924 ER PT J AU Cai, Y Zhang, XM Macklin, LN Cai, HB Luo, XG Oddo, S LaFerla, FM Struble, RG Rose, GM Patrylo, PR Yan, XX AF Cai, Yan Zhang, Xue-Mei Macklin, Lauren N. Cai, Huaibin Luo, Xue-Gang Oddo, Salvatore LaFerla, Frank M. Struble, Robert G. Rose, Gregory M. Patrylo, Peter R. Yan, Xiao-Xin TI BACE1 Elevation is Involved in Amyloid Plaque Development in the Triple Transgenic Model of Alzheimer's Disease: Differential A beta Antibody Labeling of Early-Onset Axon Terminal Pathology SO NEUROTOXICITY RESEARCH LA English DT Article DE Amyloid plaque; Axonal pathology; Synaptoplasticity; Aging; Dementia ID BETA-SECRETASE-1 ELEVATION; CEREBRAL-CORTEX; MESSENGER-RNA; MOUSE-BRAIN; MICE; PATHOGENESIS; EXPRESSION; PRESENILIN-1; SECRETASE; IMMUNOREACTIVITY AB beta-amyloid precursor protein (APP) and presenilins mutations cause early-onset familial Alzheimer's disease (FAD). Some FAD-based mouse models produce amyloid plaques, others do not. beta-Amyloid (A beta) deposition can manifest as compact and diffuse plaques; it is unclear why the same A beta molecules aggregate in different patterns. Is there a basic cellular process governing A beta plaque pathogenesis? We showed in some FAD mouse models that compact plaque formation is associated with a progressive axonal pathology inherent with increased expression of beta-secretase (BACE1), the enzyme initiating the amyloidogenic processing of APP. A monoclonal A beta antibody, 3D6, visualized distinct axon terminal labeling before plaque onset. The present study was set to understand BACE1 and axonal changes relative to diffuse plaque development and to further characterize the novel axonal A beta antibody immunoreactivity (IR), using triple transgenic AD (3xTg-AD) mice as experimental model. Diffuse-like plaques existed in the forebrain in aged transgenics and were regionally associated with increased BACE1 labeled swollen/sprouting axon terminals. Increased BACE1/3D6 IR at axon terminals occurred in young animals before plaque onset. These axonal elements were also co-labeled by other antibodies targeting the N-terminal and mid-region of A beta domain and the C-terminal of APP, but not co-labeled by antibodies against the A beta C-terminal and APP N-terminal. The results suggest that amyloidogenic axonal pathology precedes diffuse plaque formation in the 3xTg-AD mice, and that the early-onset axonal A beta antibody IR in transgenic models of AD might relate to a cross-reactivity of putative APP beta-carboxyl terminal fragments. C1 [Cai, Yan; Luo, Xue-Gang; Yan, Xiao-Xin] Cent S Univ, Xiangya Sch Med, Dept Human Anat & Neurobiol, Changsha 410013, Hunan, Peoples R China. [Cai, Yan; Zhang, Xue-Mei; Rose, Gregory M.; Patrylo, Peter R.; Yan, Xiao-Xin] So Illinois Univ, Sch Med, Dept Anat, Carbondale, IL 62901 USA. [Cai, Yan; Macklin, Lauren N.; Patrylo, Peter R.] So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. [Zhang, Xue-Mei] Harbin Med Coll, Affiliated Hosp 2, Dept Neurol, Harbin 150086, Peoples R China. [Cai, Huaibin] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Oddo, Salvatore] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Oddo, Salvatore] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [LaFerla, Frank M.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA. [Struble, Robert G.] So Illinois Univ, Sch Med, Ctr Alzheimers Dis, Springfield, IL 62794 USA. RP Yan, XX (reprint author), Cent S Univ, Xiangya Sch Med, Dept Human Anat & Neurobiol, Changsha 410013, Hunan, Peoples R China. EM yanxiaoxin@csu.edu.cn RI Cai, Huaibin/H-3359-2013 OI Cai, Huaibin/0000-0002-8596-6108 FU Illinois Department of Public Health; National Institute of Health [1R21NS056371]; Southern Illinois University Center for Alzheimer's disease and related disorders; National Institute on Aging; Central South University FX This study was supported in part by Illinois Department of Public Health (X.X.Y.), National Institute of Health (1R21NS056371 to P.R.P.), Southern Illinois University Center for Alzheimer's disease and related disorders (X.X.Y., P.R.P., R.G.S.), intramural program of the National Institute on Aging (H.C.), and Central South University (X.X.Y.). We thank Elan Pharmaceuticals and Drs. H. Akiyama, H. Mori, E. Koo, and P. Davis for providing antibodies. NR 34 TC 20 Z9 21 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PD FEB PY 2012 VL 21 IS 2 BP 160 EP 174 DI 10.1007/s12640-011-9256-9 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 869NK UT WOS:000298604700003 PM 21725719 ER PT J AU Li, M Ivanov, V Mizuuchi, M Mizuuchi, K Craigie, R AF Li, Min Ivanov, Vassili Mizuuchi, Michiyo Mizuuchi, Kiyoshi Craigie, Robert TI DNA requirements for assembly and stability of HIV-1 intasomes SO PROTEIN SCIENCE LA English DT Article DE FRET; anisotropy; site-specific recombination; retrovirus; integrase; integration; nucleoprotein complex ID RETROVIRAL DNA; STRAND TRANSFER; INTEGRATION; COMPLEX AB Integration of viral DNA into the host genome is an essential step in retroviral replication that is mediated by a stable nucleoprotein complex comprising a tetramer of integrase bridging the two ends of the viral DNA in a stable synaptic complex (SSC) or intasome. Assembly of HIV-1 intasomes requires several hundred base pairs of nonspecific internal DNA in addition to the terminal viral DNA sequence that is protected in footprinting experiments. We find that only one of the viral DNA ends in the intasome requires long-nonspecific internal DNA for intasome assembly. Although intasomes are unstable in solution when the nonspecific internal DNA is cut off after assembly, they are stable in agarose gels. These complexes are indistinguishable from SSCs with nonspecific internal DNA in Forster resonance energy transfer (FRET) experiments suggesting the interactions with the viral DNA and integrase tetramer are the same regardless of the presence of nonspecific internal DNA. We discuss models of how the internal DNA contributes to intasome assembly and stability. FRET is exquisitely sensitive to the distance between the fluorophores and given certain assumptions can be translated to distance measurements. We anticipated that a set of such distance constraints would provide a map of the DNA path within the intasome. In reality, the constraints we could impose from the FRET data were quite weak allowing a wide envelope for the possible path. We discuss the difficulties of converting the FRET signal to absolute distance within nucleoprotein complexes. C1 [Li, Min; Ivanov, Vassili; Mizuuchi, Michiyo; Mizuuchi, Kiyoshi; Craigie, Robert] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Craigie, R (reprint author), Bldg 5,Room 301,5 Mem Dr, Bethesda, MD 20892 USA. EM bobc@helix.nih.gov FU NIDDK, NIH; Office of the Director of the NIH FX Grant sponsors: Intramural Program of NIDDK, NIH; AIDS Targeted Antiviral Program of the Office of the Director of the NIH. NR 13 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD FEB PY 2012 VL 21 IS 2 BP 249 EP 257 DI 10.1002/pro.2010 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 877UZ UT WOS:000299209500011 PM 22124978 ER PT J AU Sahlberg, AS Ruuska, M Colbert, RA Granfors, K Penttinen, MA AF Sahlberg, A. S. Ruuska, M. Colbert, R. A. Granfors, K. Penttinen, M. A. TI Altered PKR Signalling and C?/?EBP ss Expression is Associated with HLA-B27 Expression in Monocytic Cells SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE PKR; ENDOPLASMIC-RETICULUM STRESS; REACTIVE ARTHRITIS; MESSENGER-RNA; SALMONELLA-ENTERITIDIS; YERSINIA ANTIGENS; TRANSGENIC RATS; BREAST-CANCER; UP-REGULATION; B-POCKET AB Infection caused by certain gram-negative bacteria, e.g. Salmonella, can trigger inflammatory joint disease reactive arthritis (ReA). It is suggested that the disease-triggering bacteria or bacterial components persist in patients for an abnormally long time. Development of ReA is strongly associated with tissue antigen HLA-B27. Previously, we reported an enhanced replication of Salmonella enteritidis and altered p38 MAP kinase signalling in HLA-B27-expressing monocytic cells. Here we aimed to investigate the role of HLA-B27 in regulation of double-stranded RNA-activated kinase (PKR)-related signalling in Salmonella-infected or Salmonella lipopolysaccharide (LPS)-stimulated human U937 monocytic cells, as PKR has been reported to modify p38 signalling in Salmonella-infected cells. In cells expressing HLA-B27, PKR is overexpressed and hypophosphorylated, and the expression of transcription factor CCAAT enhancer binding protein beta (C/EBP beta) is increased upon Salmonella infection and LPS stimulation. The expression of C/EBP beta is PKR-dependent in LPS-stimulated mock cells, whereas in LPS-stimulated B27 cells the majority of C/EBP beta is expressed in a PKR-independent manner. Our results show that the expression of HLA-B27 disturbs the PKR-mediated signalling pathway. Moreover, altered signalling is related to misfolding-linked Glu45 in the B pocket of the HLA-B27 heavy chain. We suggest that the expression of HLA-B27 HCs modulates the intracellular environment of monocyte/macrophages and the mechanisms that are important in eliminating intracellular S. enteritidis by altering the intracellular signalling. This phenomenon is at least partly dependent on the misfolding feature of the B27 molecule. These observations offer a novel mechanism by which HLA-B27 may modulate inflammatory response induced by ReA-triggering bacteria. C1 [Sahlberg, A. S.] Natl Inst Hlth & Welf, Dept Infect Dis Surveillance & Control, FIN-20520 Turku, Finland. [Colbert, R. A.] NIAMS, NIH, Bethesda, MD USA. [Penttinen, M. A.] Univ Turku, Dept Med Microbiol, Turku, Finland. RP Sahlberg, AS (reprint author), Natl Inst Hlth & Welf, Dept Infect Dis Surveillance & Control, Kiinamyllynkatu 13, FIN-20520 Turku, Finland. EM anna.sahlberg@utu.fi FU Academy of Finland; Sigrid Juselius Foundation; National Institutes of Health (NIH) [R01-AR-46177, R01-AR-48372] FX We thank Joel D. Taurog for providing the HLA-B27 genomic DNA. Tuija Turjas and Tuula Rantasalo are warmly thanked for their skillful technical assistance. Study was supported by grants from the Academy of Finland, the Sigrid Juselius Foundation and National Institutes of Health (NIH, R01-AR-46177 and R01-AR-48372). NR 49 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD FEB PY 2012 VL 75 IS 2 BP 184 EP 192 DI 10.1111/j.1365-3083.2011.02648.x PG 9 WC Immunology SC Immunology GA 874VE UT WOS:000298985400007 PM 21988375 ER PT J AU Peters, S Kromhout, H Olsson, AC Wichmann, HE Bruske, I Consonni, D Landi, MT Caporaso, N Siemiatycki, J Richiardi, L Mirabelli, D Simonato, L Gustavsson, P Plato, N Jockel, KH Ahrens, W Pohlabeln, H Boffetta, P Brennan, P Zaridze, D Cassidy, A Lissowska, J Szeszenia-Dabrowska, N Rudnai, P Fabianova, E Forastiere, F Bencko, V Foretova, L Janout, V Stucker, I Dumitru, RS Benhamou, S Bueno-de-Mesquita, B Kendzia, B Pesch, B Straif, K Bruning, T Vermeulen, R AF Peters, Susan Kromhout, Hans Olsson, Ann C. Wichmann, Heinz-Erich Brueske, Irene Consonni, Dario Landi, Maria Teresa Caporaso, Neil Siemiatycki, Jack Richiardi, Lorenzo Mirabelli, Dario Simonato, Lorenzo Gustavsson, Per Plato, Nils Joeckel, Karl-Heinz Ahrens, Wolfgang Pohlabeln, Hermann Boffetta, Paolo Brennan, Paul Zaridze, David Cassidy, Adrian Lissowska, Jolanta Szeszenia-Dabrowska, Neonila Rudnai, Peter Fabianova, Eleonora Forastiere, Francesco Bencko, Vladimir Foretova, Lenka Janout, Vladimir Stuecker, Isabelle Dumitru, Rodica Stanescu Benhamou, Simone Bueno-de-Mesquita, Bas Kendzia, Benjamin Pesch, Beate Straif, Kurt Bruening, Thomas Vermeulen, Roel TI Occupational exposure to organic dust increases lung cancer risk in the general population SO THORAX LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; WORKERS; CARCINOGENS; EUROPE AB Background Organic dust is a complex mixture of particulate matter from microbial, plant or animal origin. Occupations with exposure to animal products have been associated with an increased lung cancer risk, while exposure to microbial components (eg, endotoxin) has been associated with a decreased risk. To date there has not been a comprehensive evaluation of the possible association between occupational organic dust exposure (and its specific constituents) and lung cancer risk in the general population. Methods The SYNERGY project has pooled information on lifetime working and smoking from 13 300 lung cancer cases and 16 273 controls from 11 case-control studies conducted in Europe and Canada. A newly developed general population job-exposure matrix (assigning no, low or high exposure to organic dust, endotoxin, and contact with animals or fresh animal products) was applied to determine level of exposure. ORs for lung cancer were estimated by logistic regression, adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk. Results Occupational organic dust exposure was associated with increased lung cancer risk. The second to the fourth quartile of cumulative exposure showed significant risk estimates ranging from 1.12 to 1.24 in a dose-dependent manner (p<0.001). This association remained in the highest quartile after restricting analyses to subjects without chronic obstructive pulmonary disease or asthma. No association was observed between lung cancer and exposure to endotoxin or contact with animals or animal products. Conclusion Occupational exposure to organic dust was associated with increased lung cancer risk in this large pooled case-control study. C1 [Peters, Susan; Kromhout, Hans; Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Environm Epidemiol Div, NL-3508 TD Utrecht, Netherlands. [Olsson, Ann C.; Brennan, Paul; Straif, Kurt] Int Agcy Res Canc, F-69372 Lyon, France. [Olsson, Ann C.; Gustavsson, Per; Plato, Nils] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Wichmann, Heinz-Erich; Brueske, Irene] Deutsch Forschungszentrum Gesundheit & Umwelt, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany. [Wichmann, Heinz-Erich] Univ Munich, Inst Med Informat Biometrie Epidemiol, Munich, Germany. [Consonni, Dario] Fdn IRCCS Ca Grandad Osped Maggiore Policlin, Epidemiol Unit, Milan, Italy. [Landi, Maria Teresa; Caporaso, Neil] NCI, Bethesda, MD 20892 USA. [Siemiatycki, Jack] Univ Montreal, Univ Montreal Hosp Ctr, Res Ctr, Montreal, PQ, Canada. [Richiardi, Lorenzo; Mirabelli, Dario] CPO Piemonte, Canc Epidemiol Unit, Turin, Italy. [Richiardi, Lorenzo; Mirabelli, Dario] Univ Turin, Turin, Italy. [Simonato, Lorenzo] Univ Padua, Sch Med, Dept Environm Med & Publ Hlth, Padua, Italy. [Joeckel, Karl-Heinz] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Ahrens, Wolfgang; Pohlabeln, Hermann] Bremen Inst Prevent Res & Social Med, Bremen, Germany. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [Zaridze, David] Russian Canc Res Ctr, Moscow, Russia. [Cassidy, Adrian] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Programme, Liverpool L69 3BX, Merseyside, England. [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Lodz, Poland. [Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary. [Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia. [Forastiere, Francesco] Reg Hlth Serv, Dept Epidemiol, Rome, Italy. [Bencko, Vladimir] Charles Univ Prague, Inst Hyg & Epidemiol, Fac Med 1, Prague, Czech Republic. [Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic. [Janout, Vladimir] Palacky Univ, Fac Med, CR-77147 Olomouc, Czech Republic. [Stuecker, Isabelle] INSERM, IFR69, U754, Villejuif, France. [Dumitru, Rodica Stanescu] Inst Publ Hlth, Bucharest, Romania. [Benhamou, Simone] INSERM, U946, Paris, France. [Bueno-de-Mesquita, Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Kendzia, Benjamin; Pesch, Beate; Bruening, Thomas] Univ Bochum, German Social Accid Insuranced Inst, Inst Prevent & Occupat Med, Bochum, Germany. [Vermeulen, Roel] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. RP Peters, S (reprint author), Univ Utrecht, Inst Risk Assessment Sci, Environm Epidemiol Div, POB 80178, NL-3508 TD Utrecht, Netherlands. EM s.peters@uu.nl RI Vermeulen, Roel/F-8037-2011; Peters, Susan/A-5845-2013; Zaridze, David/K-5605-2013; Bruske, Irene/N-3125-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; Bruning, Thomas/G-8120-2015; Benhamou, Simone/K-6554-2015; Forastiere, Francesco/J-9067-2016; Consonni, Dario/K-7943-2016; OI Peters, Susan/0000-0001-5662-1971; Ahrens, Wolfgang/0000-0003-3777-570X; richiardi, lorenzo/0000-0003-0316-9402; Vermeulen, Roel/0000-0003-4082-8163; Bruning, Thomas/0000-0001-9560-5464; Forastiere, Francesco/0000-0002-9162-5684; Consonni, Dario/0000-0002-8935-3843; Lissowska, Jolanta/0000-0003-2695-5799 FU German Social Accident Insurance (DGUV); International Agency for Research on Cancer (IARC); Institute for Prevention and Occupational Medicine of the DGUV; Institute of the Ruhr-University Bochum (IPA); Institute for Risk Assessment Sciences (IRAS) at Utrecht University FX The SYNERGY project is funded by the German Social Accident Insurance (DGUV), and is coordinated by the International Agency for Research on Cancer (IARC), the Institute for Prevention and Occupational Medicine of the DGUV, Institute of the Ruhr-University Bochum (IPA) and the Institute for Risk Assessment Sciences (IRAS) at Utrecht University. NR 22 TC 20 Z9 20 U1 1 U2 16 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 EI 1468-3296 J9 THORAX JI Thorax PD FEB PY 2012 VL 67 IS 2 BP 111 EP 116 DI 10.1136/thoraxjnl-2011-200716 PG 6 WC Respiratory System SC Respiratory System GA 879IA UT WOS:000299321700006 PM 21856697 ER PT J AU O'Donghaile, D Kelley, W Klein, HG Flegel, WA AF O'Donghaile, Diarmaid Kelley, Walter Klein, Harvey G. Flegel, Willy A. TI Recommendations for transfusion in ABO-incompatible hematopoietic stem cell transplantation SO TRANSFUSION LA English DT Letter ID PLATELETS C1 [O'Donghaile, Diarmaid; Kelley, Walter; Klein, Harvey G.; Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP O'Donghaile, D (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EM bill.flegel@nih.gov OI Flegel, Willy Albrecht/0000-0002-1631-7198 FU Intramural NIH HHS [Z99 CL999999] NR 5 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 2012 VL 52 IS 2 BP 456 EP 458 DI 10.1111/j.1537-2995.2011.03465.x PG 3 WC Hematology SC Hematology GA 875NO UT WOS:000299038200035 PM 22239215 ER PT J AU Langenkamp, E Zwiers, PJ Moorlag, HE Leenders, WP Croix, BS Molema, G AF Langenkamp, Elise Zwiers, Peter J. Moorlag, Henk E. Leenders, William P. Croix, Brad St. Molema, Grietje TI Vascular endothelial growth factor receptor 2 inhibition in-vivo affects tumor vasculature in a tumor type-dependent way and downregulates vascular endothelial growth factor receptor 2 protein without a prominent role for miR-296 SO ANTI-CANCER DRUGS LA English DT Article DE receptor tyrosine kinase inhibitors; tumor angiogenesis; vascular gene expression; vascular stabilization; vascular endothelial growth factor receptor 2 inhibition ID ANTIANGIOGENIC THERAPY; NEGATIVE REGULATOR; ANTITUMOR-ACTIVITY; KINASE INHIBITORS; FACTOR-A; VEGF; ANGIOGENESIS; CANCER; CELLS; ZD6474 AB The precise molecular effects that antiangiogenic drugs exert on tumor vasculature remain to be poorly understood. We therefore set out to investigate the molecular and architectural changes that occur in the vasculature of two different tumor types that both respond to vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor therapy. Mice bearing Lewis lung carcinoma (LLC) or B16.F10 melanoma were treated with vandetanib (ZD6474), a VEGFR2/epidermal growth factor receptor (EGFR)/REarranged during Transfection (RET) kinase inhibitor, resulting in a significant 80% reduction in tumor outgrowth. Although in LLC the vascular density was not affected by vandetanib treatment, it was significantly decreased in B16.F10. In LLC, vandetanib treatment induced a shift in vascular gene expression toward stabilization, as demonstrated by upregulation of Tie2 and N-cadherin and downregulation of Ang2 and integrin beta 3. In contrast, only eNOS and P-selectin responded to vandetanib treatment in B16.F10 vasculature. Strikingly, vandetanib reduced protein expression of VEGFR2 in both models, whereas mRNA remained unaffected. Analysis of miR-296 expression allowed us to exclude a role for the recently proposed microRNA-296 in VEGFR2 posttranslational control in LLC and B16.F10 in vivo. Our data demonstrate that VEGFR2/EGFR inhibition through vandetanib slows down both LLC and B16.F10 tumor growth. Yet, the underlying molecular changes in the vasculature that orchestrate the antitumor effect differ between tumor types. Importantly, in both models, vandetanib treatment induced loss of its pharmacological target, which was not directly related to miR-296 expression. Validation of our observations in tumor biopsies from VEGFR2 inhibitor-treated patients will be essential to unravel the effects of VEGFR2 inhibitor therapy on tumor vasculature in relation to therapeutic efficacy. Anti-Cancer Drugs 23: 161-172 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Langenkamp, Elise; Zwiers, Peter J.; Moorlag, Henk E.; Molema, Grietje] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Med Biol Sect, NL-9713 GZ Groningen, Netherlands. [Leenders, William P.] Univ Med Ctr Nijmegen, Dept Pathol, Nijmegen, Netherlands. [Croix, Brad St.] NCI, Mouse Canc Genet Program, Tumor Angiogenesis Sect, Frederick, MD 21701 USA. RP Molema, G (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Med Biol Sect, Internal Postal Code EA11,Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM g.molema01@umcg.nl OI Molema, Grietje/0000-0002-4147-6676 FU University of Groningen FX This research was funded by the University of Groningen. NR 45 TC 4 Z9 5 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD FEB PY 2012 VL 23 IS 2 BP 161 EP 172 DI 10.1097/CAD.0b013e32834dc279 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 870AY UT WOS:000298642700004 PM 22075979 ER PT J AU Malinouski, M Kehr, S Finney, L Vogt, S Carlson, BA Seravalli, J Jin, R Handy, DE Park, TJ Loscalzo, J Hatfield, DL Gladyshev, VN AF Malinouski, Mikalai Kehr, Sebastian Finney, Lydia Vogt, Stefan Carlson, Bradley A. Seravalli, Javier Jin, Richard Handy, Diane E. Park, Thomas J. Loscalzo, Joseph Hatfield, Dolph L. Gladyshev, Vadim N. TI High-Resolution Imaging of Selenium in Kidneys: A Localized Selenium Pool Associated with Glutathione Peroxidase 3 SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID NAKED MOLE-RAT; PREVENTION TRIAL SELECT; TUBULE CELLS; VITAMIN-E; CANCER; MOUSE; SPERMATOGENESIS; SELENOPROTEINS; SELENOCYSTEINE; RESISTANCE AB Aim: Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Results: Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA([Ser]Sec) and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts of the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. Innovation: We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. Conclusion: XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution. Antioxid. Redox Signal. 16, 185-192. C1 [Gladyshev, Vadim N.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Malinouski, Mikalai; Jin, Richard; Handy, Diane E.; Loscalzo, Joseph; Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Malinouski, Mikalai; Kehr, Sebastian; Seravalli, Javier] Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA. [Finney, Lydia; Vogt, Stefan] Argonne Natl Lab, X Ray Sci Div, Argonne, IL 60439 USA. [Finney, Lydia] Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. [Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Park, Thomas J.] Univ Illinois, Dept Biol Sci, Chicago, IL 60680 USA. RP Gladyshev, VN (reprint author), Harvard Univ, Sch Med, Dept Med, New Res Bldg,Room 435,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vgladyshev@rics.bwh.harvard.edu RI Gladyshev, Vadim/A-9894-2013; Vogt, Stefan/B-9547-2009; Vogt, Stefan/J-7937-2013 OI Vogt, Stefan/0000-0002-8034-5513; Vogt, Stefan/0000-0002-8034-5513 FU National Institutes of Health [GM061603, CA080946, HL061795, HL070819, HL048743]; National Institutes of Health, National Cancer Institute, Center for Cancer Research; U.S. DOE [DE-AC02-06CH11357] FX We thank Drs. Raymond Burk and Kristina Hill (Vanderbilt University) for providing tissues of SelP knockout mice. This work was supported by National Institutes of Health grants to VNG (GM061603 and CA080946) and JL (HL061795, HL070819, and HL048743), and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, to DLH. Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. NR 33 TC 22 Z9 22 U1 3 U2 11 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD FEB PY 2012 VL 16 IS 3 BP 185 EP 192 DI 10.1089/ars.2011.3997 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 863HM UT WOS:000298153400001 PM 21854231 ER PT J AU Rose, EJ Ross, TJ Salmeron, BJ Lee, M Shakleya, DM Huestis, M Stein, EA AF Rose, Emma Jane Ross, Thomas J. Salmeron, Betty Jo Lee, Mary Shakleya, Diaa M. Huestis, Marilyn Stein, Elliot A. TI Chronic Exposure to Nicotine Is Associated with Reduced Reward-Related Activity in the Striatum but not the Midbrain SO BIOLOGICAL PSYCHIATRY LA English DT Article DE fMRI; nicotine; reward; smoking; striatum; temporal difference error ID VENTRAL TEGMENTAL AREA; EVENT-RELATED FMRI; CIGARETTE-SMOKING; DOPAMINE RELEASE; ACETYLCHOLINE-RECEPTORS; TEMPORAL PREDICTION; DECISION-MAKING; NEURAL RESPONSE; FAGERSTROM TEST; HUMAN BRAIN AB Background: The reinforcing effects of nicotine are mediated by brain regions that also support temporal difference error (TDE) processing; yet, the impact of nicotine on TDE is undetermined. Methods: Dependent smokers (n = 21) and matched control subjects (n = 21) were trained to associate a juice reward with a visual cue in a classical conditioning paradigm. Subjects subsequently underwent functional magnetic resonance imaging sessions in which they were exposed to trials where they either received juice as temporally predicted or where the juice was withheld (negative TDE) and later received unexpectedly (positive TDE). Subjects were scanned in two sessions that were identical, except that smokers had a transdermal nicotine (21 mg) or placebo patch placed before scanning. Analysis focused on regions along the trajectory of mesocorticolimbic and nigrostriatal dopaminergic pathways. Results: There was a reduction in TDE-related function in smokers in the striatum, which did not differ as a function of patch manipulation but was predicted by the duration (years) of smoking. Activation in midbrain regions was not impacted by group or drug condition. Conclusions: These data suggest a differential effect of smoking status on the neural substrates of reward in distinct dopaminergic pathway regions, which may be partially attributable to chronic nicotine exposure. The failure of transdermal nicotine to alter reward-related functional processes, either within smokers or between smokers and control subjects, implies that acute nicotine patch administration is insufficient to modify reward processing, which has been linked to abstinence-induced anhedonia in smokers and may play a critical role in smoking relapse. C1 [Rose, Emma Jane; Ross, Thomas J.; Salmeron, Betty Jo; Lee, Mary; Stein, Elliot A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD USA. [Shakleya, Diaa M.; Huestis, Marilyn] Natl Inst Drug Abuse, Chem & Drug Metab Branch, NIH, Baltimore, MD USA. RP Rose, EJ (reprint author), Trinity Coll Dublin, Dept Psychiat, Neuropsychiat Genet Grp, Dublin, Ireland. EM rosee@tcd.ie RI Ross, Thomas/B-7469-2008; Rose, Emma/A-9960-2010; Salmeron, Betty Jo/M-1793-2016 OI Ross, Thomas/0000-0002-7745-3572; Rose, Emma/0000-0001-5365-4794; Salmeron, Betty Jo/0000-0003-1699-9333 FU National Institute on Drug Abuse (NIDA) FX This study was supported by the National Institute on Drug Abuse (NIDA), Intramural Research Program. NR 79 TC 25 Z9 25 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 2012 VL 71 IS 3 BP 206 EP 213 DI 10.1016/j.biopsych.2011.09.013 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 875DP UT WOS:000299010900006 PM 22032832 ER PT J AU Elking, DM Perera, L Pedersen, LG AF Elking, Dennis M. Perera, Lalith Pedersen, Lee G. TI HPAM: Hirshfeld partitioned atomic multipoles SO COMPUTER PHYSICS COMMUNICATIONS LA English DT Article DE Atomic multipoles; Hirshfeld charges; Dipole; Quadrupole ID MOLECULAR ELECTROSTATIC POTENTIALS; FORCE-FIELD; CHARGE-DISTRIBUTION; FLUCTUATING CHARGE; WATER; SIMULATION; MOMENTS; QUANTUM; MODELS; PARAMETERIZATION AB An implementation of the Hirshfeld (HD) and Hirshfeld-Iterated (HD-I) atomic charge density partitioning schemes is described. Atomic charges and atomic multipoles are calculated from the HD and HD-I atomic charge densities for arbitrary atomic multipole rank I(max) on molecules of arbitrary shape and size. The HD and HD-I atomic charges/multipoles are tested by comparing molecular multipole moments and the electrostatic potential (ESP) surrounding a molecule with their reference ab initio values. In general. the HD-I atomic charges/multipoles are found to better reproduce ab initio electrostatic properties over HD atomic charges/multipoles. A systematic increase in precision for reproducing ab initio electrostatic properties is demonstrated by increasing the atomic multipole rank from I(max) = 0 (atomic charges) to I(max) = 4 (atomic hexadecapoles). Both HD and HD-I atomic multipoles up to rank I(max) are shown to exactly reproduce ab initio molecular multipole moments of rank L for L <= I(max) In addition, molecular dipole moments calculated by HD, HD-I, and ChelpG atomic charges only (I(max) = 0) are compared with reference ab initio values. Significant errors in reproducing ab initio molecular dipole moments are found if only HD or HD-I atomic charges used. Program summary Program title: HPAM Catalogue identifier: AEKP_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEKP_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License v2 No. of lines in distributed program, including test data, etc.: 500 809 No. of bytes in distributed program, including test data, etc.: 13 424 494 Distribution format: tarp Programming language: C Computer: Any Operating system: Linux RAM: Typically, a few hundred megabytes Classification: 16.13 External routines: The program requires 'formatted checkpoint' files obtained from the Gaussian 03 or Gaussian 09 quantum chemistry program. Nature of problem: An ab initio molecular charge density rho(mol)(r) is partitioned into Hirshfeld (HD) and Hirshfeld-lterated (HD-I) atomic charge densities rho(a)(r) on a grid. Atomic charges q(a) and multipoles Q(lm)(a) are calculated from the partitioned atomic charge densities rho(a)(r) by numerical integration. Solution method: Molecular and isolated atomic grids are generated for the molecule of interest. The ab initio density matrix P(mu nu) and basis functions chi(mu)(r) are read in from 'formatted checkpoint' files obtained from the Gaussian 03 or 09 quantum chemistry programs. The ab initio density is evaluated for the molecule and the isolated atoms/atomic ions on grids and used to construct Hirshfeld (HD) and Hirshfeld-1 (HD-I) partitioned atomic charges densities rho(a)(r), which are used to calculate atomic charges qa and atomic multipoles Q(lm)(a), by integration. Restrictions: The ab initio density matrix can be calculated at the HF, DEL MP2, or CCSD levels with ab initio Gaussian basis sets that include up to s, p, d, f, g functions for either closed shell or open shell molecules. Running time: The running time varies with the size of the molecule, the size of the ab initio basis set, and the coarseness of the desired grid. The run time can range from a minute or less for water to similar to 15 minutes for neopentane. (C) 2011 Elsevier B.V. All rights reserved. C1 [Elking, Dennis M.; Pedersen, Lee G.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Perera, Lalith; Pedersen, Lee G.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Elking, DM (reprint author), Openeye Sci Software, 9 Bisbee Court,Suite D, Santa Fe, NM 87508 USA. EM denny@eyesopen.com RI perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013 OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861 FU National Institute of Health [HL-06350]; National Science Foundation [FRG DMR 084549]; NIH-National Institute of Environmental Health Sciences [Z01 ES125392] FX This research was supported by the National Institute of Health (HL-06350) and National Science Foundation (FRG DMR 084549) to LGP This research was supported (in part) by the Intramural Research Program of the NIH-National Institute of Environmental Health Sciences (Z01 ES125392). DME thanks the NIEHS, RIP, NC for providing visitor status for the year this work was accomplished. NR 51 TC 7 Z9 7 U1 1 U2 26 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-4655 J9 COMPUT PHYS COMMUN JI Comput. Phys. Commun. PD FEB PY 2012 VL 183 IS 2 BP 390 EP 397 DI 10.1016/j.cpc.2011.10.003 PG 8 WC Computer Science, Interdisciplinary Applications; Physics, Mathematical SC Computer Science; Physics GA 868OA UT WOS:000298531400020 PM 22140274 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 Augusto, DG Zehnder-Alves, L Pincerati, MR Martin, MP Carrington, M Petzl-Erler, ML AF Augusto, D. G. Zehnder-Alves, L. Pincerati, M. R. Martin, M. P. Carrington, M. Petzl-Erler, Maria Luiza TI Diversity of the KIR gene cluster in an urban Brazilian population SO IMMUNOGENETICS LA English DT Article DE KIR genes; KIR diversity; Brazilian population; HLA ligands; 2DL4 allele frequencies ID IMMUNOGLOBULIN-LIKE RECEPTOR; NATURAL-KILLER-CELLS; CHROMOSOME 19Q13.4; HAPLOTYPE ANALYSIS; NK CELLS; HLA-C; KIR2DL4; ALLELES; POLYMORPHISMS; DISEASE AB The activity of natural killer cells depends on the balance between activating and inhibitory signals coming from their receptors. Among these are the killer cell immunoglobulin-like receptors (KIR) that recognize specific HLA class I allotypes. Here we characterized KIR genetic diversity and their HLA ligands in the population of Curitiba, Parana State (n = 164), and compared it with other worldwide populations. The distribution of 2DL4 alleles was also analyzed. The Curitiba population did not differ significantly from European and Euro-descendant populations, but as an admixed population showed higher genetic diversity. We found 27 KIR profiles, many of them uncommon in European populations, in agreement with the elevated historically recent gene flow in the study population. The frequencies of KIR genes and their respective HLA ligands were distributed independently and none of the analyzed individuals lacked functional KIR-HLA ligand combinations. KIR gene frequencies of 33 worldwide populations were consistent with geographic and ethnic distribution, in agreement with demography being the major factor shaping the observed gene content diversity of the KIR locus. C1 [Augusto, D. G.; Zehnder-Alves, L.; Petzl-Erler, Maria Luiza] Univ Fed Parana, Dept Genet, Lab Genet Mol Humana, BR-81531980 Curitiba, Parana, Brazil. [Pincerati, M. R.] Univ Sao Paulo, Dept Genet & Biol Evolut, BR-05508090 Sao Paulo, Brazil. [Martin, M. P.; Carrington, M.] NCI Frederick, SAIC Frederick Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD 21702 USA. [Carrington, M.] MIT, Gen Hosp, Ragon Inst Massachusetts, Boston, MA 02114 USA. RP Petzl-Erler, ML (reprint author), Univ Fed Parana, Dept Genet, Lab Genet Mol Humana, Caixa Postal 19071, BR-81531980 Curitiba, Parana, Brazil. EM perler@ufpr.br RI Augusto, Danillo/F-3147-2013; Petzl-Erler, Maria-Luiza/H-8221-2012 OI Petzl-Erler, Maria-Luiza/0000-0002-0345-5276 FU Laboratory of Human Molecular Genetics at the Department of Genetics of the Federal University of Parana; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); PRONEX; Institutos do Milenio; Fundacao Araucaria; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX We thank the staff of the Laboratory of Human Molecular Genetics at the Department of Genetics of the Federal University of Parana for assistance and support. Special thanks to Liana Alves de Oliveira for her expertise and valuable comments. We also thank Fuh-Mei Duh and Colm O'huigin for helpful advice and Maria Dias da Silva for reading this manuscript. This project received financial support from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), PRONEX, Institutos do Milenio, Fundacao Araucaria, Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES). This project was funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 52 TC 13 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD FEB PY 2012 VL 64 IS 2 BP 143 EP 152 DI 10.1007/s00251-011-0565-1 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 876AT UT WOS:000299079900007 PM 21850526 ER PT J AU Little, MP Kleinerman, RA Stiller, CA Li, GQ Kroll, ME Murphy, MFG AF Little, Mark P. Kleinerman, Ruth A. Stiller, Charles A. Li, Guangquan Kroll, Mary E. Murphy, Michael F. G. TI Analysis of retinoblastoma age incidence data using a fully stochastic cancer model SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE retinoblastoma; carcinogenesis modeling; two-hit theory; stochastic MVK model; RB1 gene ID HEREDITARY RETINOBLASTOMA; GENOMIC INSTABILITY; CHILDHOOD-CANCER; RB1 MUTATIONS; GENE; CARCINOGENESIS; HITS; HETEROZYGOSITY; IDENTIFICATION; PROGRESSION AB Retinoblastoma (RB) is an important ocular malignancy of childhood. It has been commonly accepted for some time that knockout of the two alleles of the RB1 gene is the principal molecular target associated with the occurrence of RB. In this article, we examine the validity of the two-hit theory for RB by comparing the fit of a stochastic model with two or more mutational stages. Unlike many such models, our model assumes a fully stochastic stem cell compartment, which is crucial to its behavior. Models are fitted to a population-based dataset comprising 1,553 cases of RB for the period 1962-2000 in Great Britain (England, Scotland and Wales). The population incidence of RB is best described by a fully stochastic model with two stages, although models with a deterministic stem cell compartment yield equivalent fit; models with three or more stages fit much less well. The results strongly suggest that knockout of the two alleles of the RB1 gene is necessary and may be largely sufficient for the development of RB, in support of Knudson's two-hit hypothesis. C1 [Little, Mark P.; Kleinerman, Ruth A.] NCI, Radiat Epidemiol Branch, DHHS, NIH,Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. [Stiller, Charles A.; Kroll, Mary E.; Murphy, Michael F. G.] Univ Oxford, Dept Paediat, Childhood Canc Res Grp, Oxford, England. [Li, Guangquan] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Kroll, Mary E.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, DHHS, NIH,Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. EM mark.little@nih.gov OI Kleinerman, Ruth/0000-0001-7415-2478; Little, Mark/0000-0003-0980-7567 FU European Commission [FI6R-CT-2003-508842, FP6-036465]; National Institutes of Health; National Cancer Institute; Division of Cancer Epidemiology and Genetics; Department of Health and the Scottish Ministers; Children with Leukaemia; Higher Education Funding Council for England FX Grant sponsor: European Commission; Grant numbers: FI6R-CT-2003-508842 (RISC-RAD), FP6-036465 (NOTE); Grant sponsors: National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics (Intramural Research Program), Department of Health and the Scottish Ministers, Children with Leukaemia, Higher Education Funding Council for England (Overseas Research Students Awards Schemes) NR 49 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 1 PY 2012 VL 130 IS 3 BP 631 EP 640 DI 10.1002/ijc.26039 PG 10 WC Oncology SC Oncology GA 869MP UT WOS:000298602500015 PM 21387305 ER PT J AU Lin, FR Maas, P Chien, W Carey, JP Ferrucci, L Thorpe, R AF Lin, Frank R. Maas, Paige Chien, Wade Carey, John P. Ferrucci, Luigi Thorpe, Roland TI Association of Skin Color, Race/Ethnicity, and Hearing Loss Among Adults in the USA SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE hearing loss; race; melanocytes; epidemiology ID PIGMENTED GUINEA-PIGS; THRESHOLD SHIFT; DIFFERENTIAL SUSCEPTIBILITY; STRIA VASCULARIS; HUMAN ALBINOS; NOISE; MELANIN; PREVALENCE; CISPLATIN; HEALTH AB Epidemiologic studies of hearing loss in adults have demonstrated that the odds of hearing loss are substantially lower in black than in white individuals. The basis of this association is unknown. We hypothesized that skin pigmentation as a marker of melanocytic functioning mediates this observed association and that skin pigmentation is associated with hearing loss independent of race/ethnicity. We analyzed cross-sectional data from 1,258 adults (20-59 years) in the 2003-2004 cycle of the National Health and Nutritional Examination Survey who had assessment of Fitzpatrick skin type and pure-tone audiometric testing. Audiometric thresholds in the worse hearing ear were used to calculate speech- (0.5-4 kHz) and high-frequency (3-8 kHz) pure-tone averages (PTA). Regression models were stratified by Fitzpatrick skin type or race/ethnicity to examine the association of each factor with hearing loss independent of the other. Models were adjusted for potential confounders (demographic, medical, and noise exposure covariates). Among all participants, race/ethnicity was associated with hearing thresholds (black participants with the best hearing followed by Hispanics and then white individuals), but these associations were not significant in analyses stratified by skin color. In contrast, in race-stratified analyses, darker-skinned Hispanics had better hearing than lighter-skinned Hispanics by an average of -2.5 dB hearing level (HL; 95% CI, -4.8 to -0.2) and -3.1 dB HL (95% CI, -5.3 to -0.8) for speech and high-frequency PTA, respectively. Associations between skin color and hearing loss were not significant in white and black participants. Our results demonstrate that skin pigmentation is independently associated with hearing loss in Hispanics and suggest that skin pigmentation as a marker of melanocytic functioning may mediate the strong association observed between race/ethnicity and hearing loss. C1 [Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA. [Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Aging & Hlth, Baltimore, MD 21287 USA. [Lin, Frank R.; Chien, Wade; Carey, John P.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. [Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Aging & Hlth, Baltimore, MD 21205 USA. [Maas, Paige] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Baltimore, MD 21225 USA. [Thorpe, Roland] Johns Hopkins Bloomberg Sch Publ Hlth, Johns Hopkins Ctr Hlth Dispar Solut, Baltimore, MD 21205 USA. [Thorpe, Roland] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD 21205 USA. RP Lin, FR (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 2024 Monument St,Suite 2-700, Baltimore, MD 21287 USA. EM flin1@jhmi.edu FU NIDCD NIH HHS [K23 DC011279] NR 35 TC 19 Z9 19 U1 2 U2 8 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 109 EP 117 DI 10.1007/s10162-011-0298-8 PG 9 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 876FF UT WOS:000299092200009 PM 22124888 ER PT J AU Lozito, TP Tuan, RS AF Lozito, Thomas P. Tuan, Rocky S. TI Endothelial cell microparticles act as centers of matrix metalloproteinsase-2 (MMP-2) activation and vascular matrix remodeling SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID MESENCHYMAL STEM-CELLS; IN-VITRO; TISSUE INHIBITORS; MEMBRANE; SURFACE; MT1-MMP; GENERATION; COMPONENTS; MECHANISM; DISEASE AB Endothelial cell (EC)-derived microparticles (MPs) are small membrane vesicles associated with various vascular pathologies. Here, we investigated the role of MPs in matrix remodeling by analyzing their interactions with the extracellular matrix. MPs were shown to bind preferentially to surfaces coated with matrix molecules, and MPs bound fibronectin via integrin aV. MPs isolated from EC-conditioned medium (Sup) were significantly enriched for matrix-altering proteases, including matrix metalloproteinases (MMPs). MPs lacked the MMP inhibitors TIMP-1 and TIMP-2 found in the Sup and, while Sup strongly inhibited MMP activities but MPs did not. In fact, MPs were shown to bind and activate both endogenous and exogenous proMMP-2. Taken together, these results indicate that MPs interact with extracellular matrices, where they localize and activate MMP-2 to modify the surrounding matrix molecules. These findings provide insights into the cellular mechanisms of vascular matrix remodeling and identify new targets of vascular pathologies. J. Cell. Physiol. 227: 534549, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Lozito, Thomas P.; Tuan, Rocky S.] Univ Pittsburgh, Sch Med, Ctr Cellular & Mol Engn, Dept Orthopaed Surg, Pittsburgh, PA 15219 USA. [Lozito, Thomas P.; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), Univ Pittsburgh, Sch Med, Ctr Cellular & Mol Engn, Dept Orthopaed Surg, 450 Technol Dr,Room 221, Pittsburgh, PA 15219 USA. EM rst13@pitt.edu FU NIAMS IRP [Z01AR41131] FX Contract grant sponsor: NIAMS IRP;; Contract grant number: Z01AR41131. NR 33 TC 19 Z9 22 U1 2 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 534 EP 549 DI 10.1002/jcp.22744 PG 16 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 862LQ UT WOS:000298092800016 PM 21437907 ER PT J AU Bornstein, MH Putnick, DL Suwalsky, JTD Venuti, P de Falco, S de Galperin, CZ Gini, M Tichovolsky, MH AF Bornstein, Marc H. Putnick, Diane L. Suwalsky, Joan T. D. Venuti, Paola de Falco, Simona Zingman de Galperin, Celia Gini, Motti Tichovolsky, Marianne Heslington TI Emotional Relationships in Mothers and Infants: Culture-Common and Community-Specific Characteristics of Dyads From Rural and Metropolitan Settings in Argentina, Italy, and the United States SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article DE cultural psychology; child/adolescent development; social development ID EUROPEAN-AMERICAN FAMILIES; CHILD-REARING VALUES; AVAILABILITY SCALES; PRESCHOOL-CHILDREN; YOUNG-CHILDREN; ATTACHMENT; PERSPECTIVE; BEHAVIOR; QUALITY; PERCEPTION AB This study uses country and regional contrasts to examine culture-common and community-specific variation in mother-infant emotional relationships. Altogether, 220 Argentine, Italian, and U.S. American mothers and their daughters and sons, living in rural and metropolitan settings, were observed at home at infant age 5 months. Both variable- and person-centered perspectives of dyadic emotional relationships were analyzed. Supporting the notion that adequate emotional relationships are a critical and culture-common characteristic of human infant development, across all samples most dyads scored in the adaptive range in terms of emotional relationships. Giving evidence of community-specific characteristics, Italian mothers were more sensitive, and Italian infants more responsive, than Argentine and U.S. mothers and infants; in addition, rural mothers were more intrusive than metropolitan mothers and rural dyads more likely than expected to be classified as midrange in emotional relationships and less likely to be classified as high in emotional relationships. Adaptive emotional relationships appear to be a culture-common characteristic of mother-infant dyads near the beginning of life, but this relational construct is moderated by a community-specific (country and regional) context. C1 [Bornstein, Marc H.; Putnick, Diane L.; Suwalsky, Joan T. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Venuti, Paola; de Falco, Simona] Univ Trent, Cognit Sci & Educ Dept, Trento, Italy. [Zingman de Galperin, Celia] Univ Belgrano, Buenos Aires, DF, Argentina. [Gini, Motti] Univ Haifa, IL-31999 Haifa, Israel. [Tichovolsky, Marianne Heslington] Univ Massachusetts, Amherst, MA 01003 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Dept Hlth & Human Serv, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov OI Putnick, Diane/0000-0002-6323-749X FU Intramural NIH HHS [Z99 HD999999] NR 138 TC 11 Z9 11 U1 3 U2 19 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD FEB PY 2012 VL 43 IS 2 BP 171 EP 197 DI 10.1177/0022022110388563 PG 27 WC Psychology, Social SC Psychology GA 873XN UT WOS:000298918900001 PM 22247569 ER PT J AU Setse, R Siberry, GK Moss, WJ Gravitt, P Wheeling, T Bohannon, B Dominguez, K AF Setse, Rosanna Siberry, George K. Moss, William J. Gravitt, Patti Wheeling, Travis Bohannon, Beverly Dominguez, Kenneth CA Legacy Consortium TI Cervical Pap Screening Cytological Abnormalities among HIV-Infected Adolescents in the LEGACY Cohort SO JOURNAL OF PEDIATRIC AND ADOLESCENT GYNECOLOGY LA English DT Article DE Cervical Pap screening; HIV infection; Adolescents ID HUMAN-IMMUNODEFICIENCY-VIRUS; SQUAMOUS INTRAEPITHELIAL LESIONS; HUMAN-PAPILLOMAVIRUS INFECTION; CANCER-SOCIETY GUIDELINE; RISK-FACTORS; PAPANICOLAOU SMEARS; SEROPOSITIVE WOMEN; NEGATIVE WOMEN; UNITED-STATES; SELF-REPORT AB Objectives: To determine the prevalence of cervical Pap screening (CPAP-S), identify factors associated with CPAP-S, and explore risk factors for abnormal cervical cytology in female adolescents with perinatally and behaviorally acquired HIV infection. Design: Cross-sectional. Setting: LEGACY is a national observational cohort chart review study of 1478 HIV-infected persons (0% (consistent with a cytostatic effect) were observed in 8 cell lines and 15 cell lines showed Relative I/O values ranging from -4.7 to -92.2% (consistent with varying degrees of cytotoxic activity). In vivo AZD8055 induced significant differences in EFS distribution compared to controls in 23 of 36 (64%) evaluable solid tumor xenografts, and 1 of 6 evaluable ALL xenografts. Intermediate activity for the time to event activity measure (EFS T/C >2) was observed in 5 of 32 (16%) solid tumor xenografts evaluable. The best response was stable disease. PD2 (progressive disease with growth delay) was observed in 20 of 36 (55.6%) evaluable solid tumor xenografts. AZD8055 significantly inhibited 4E-BP1, S6, and Akt phosphorylation following day 1 and day 4 dosing, but suppression of mTORC1 or mTORC2 signaling did not predict tumor sensitivity. C1 [Houghton, Peter J.] Nationwide Childrens Hosp, Ctr Childhood Canc, Columbus, OH 43204 USA. [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Lock, Richard; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. [Morton, Christopher L.; Billups, Catherine] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Maris, John M.] Univ Penn, Childrens Hosp, Sch Med, Philadelphia, PA 19104 USA. [Maris, John M.] Univ Penn, Childrens Hosp, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Houghton, PJ (reprint author), Nationwide Childrens Hosp, Ctr Childhood Canc, 700 Childrens Dr, Columbus, OH 43204 USA. EM peter.houghton@nationwidechildrens.org RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013; OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C. Patrick/0000-0002-2827-8536 FU National Cancer Institute [NO1-CM-42216, NO1-CM91001-03, CA21765, CA108786] FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216; NO1-CM91001-03; CA21765; CA108786. NR 34 TC 19 Z9 20 U1 0 U2 2 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2012 VL 58 IS 2 BP 191 EP 199 DI 10.1002/pbc.22935 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 864RZ UT WOS:000298259000008 PM 21337679 ER PT J AU Houghton, PJ Lock, R Carol, H Morton, CL Gorlick, R Kolb, EA Keir, ST Reynolds, CP Kang, H Maris, JM Billups, CA Zhang, MX Madden, SL Teicher, BA Smith, MA AF Houghton, Peter J. Lock, Richard Carol, Hernan Morton, Christopher L. Gorlick, Richard Kolb, E. Anders Keir, Stephen T. Reynolds, C. Patrick Kang, H. Maris, John M. Billups, Catherine A. Zhang, Mindy X. Madden, Stephen L. Teicher, Beverly A. Smith, Malcolm A. TI Testing of the topoisomerase 1 inhibitor Genz-644282 by the pediatric preclinical testing program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE developmental therapeutics; Genz-644282; preclinical testing ID REFRACTORY SOLID TUMORS; PHASE-I TRIAL; CANCER MODELS; IRINOTECAN; TOPOTECAN; XENOGRAFTS; CAMPTOTHECIN; EFFICACY; DRUG; CHILDREN AB Background Genz-644282 is a novel non-camptothecin topoisomerase I poison that is in clinical development. Procedures. Genz-644282 was tested against the PPTP in vitro panel (0.1 nM to 1 mu M), and in vivo using three times per week x 2 schedule repeated at day 21 at its maximum tolerated dose (MTD) of 4 mg/kg. Subsequently Genz-644282 was tested at 4, 3, 2, and 1 mg/kg in 3 models to assess the dose-response relationship. mRNA gene signatures predictive for Genz-644282 response in vitro were applied to select 15 tumor models that were evaluated prospectively. Results. In vitro, Genz-644282 demonstrated potent cytotoxic activity with a median IC(50) of 1.2 nM (range 0.2-21.9 nM). In vivo, Genz-644282 at its MTD (4 mg/kg) induced maintained complete responses (MCR) in 6/6 evaluable solid tumor models. At 2 mg/kg Genz-644282 induced CR or MCR in 3/3 tumor models relatively insensitive to topotecan, but there were no objective responses at 1 mg/kg. Further testing at 2 mg/kg showed that Genz-644282 induced objective regressions in 7 of 17 (41%) models. There was a significant correlation between predictive response scores based on Affymetrix U133Plus2 baseline tumor expression profiles and the observed in vivo responses to Genz-644282. Conclusions. Genz-644282 was highly active within a narrow dose range (2-4 mg/kg), typical of other topoisomerase I poisons. As with other topoisomerase I poisons, how accurately these data will translate to clinical activity will depend upon the drug exposures that can be achieved in children treated with this agent. Pediatr Blood Cancer 2012; 58: 200-209. (C) 2011 Wiley Periodicals, Inc. C1 [Houghton, Peter J.] Nationwide Childrens Hosp, Ctr Childhood Canc, Res Inst, Columbus, OH 43205 USA. [Lock, Richard; Carol, Hernan; Billups, Catherine A.] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. [Morton, Christopher L.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Reynolds, C. Patrick; Kang, H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Maris, John M.] Univ Penn, Childrens Hosp, Sch Med, Philadelphia, PA 19104 USA. [Maris, John M.] Univ Penn, Childrens Hosp, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Zhang, Mindy X.; Madden, Stephen L.] Genzyme Corp, Framingham, MA 01701 USA. [Teicher, Beverly A.] NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Houghton, PJ (reprint author), Nationwide Childrens Hosp, Ctr Childhood Canc, Res Inst, 700 Childrens Dr, Columbus, OH 43205 USA. EM Peter.Houghton@nationwidechildrens.org RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013; OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C. Patrick/0000-0002-2827-8536 FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786] FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216, CA21765, CA108786. NR 39 TC 2 Z9 2 U1 0 U2 2 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2012 VL 58 IS 2 BP 200 EP 209 DI 10.1002/pbc.23016 PG 10 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 864RZ UT WOS:000298259000009 PM 21548007 ER PT J AU Phipps, S Buckholdt, KE Fernandez, L Wiener, L Kupst, MJ Madan-Swain, A Mullins, L Robert, R Sahler, OJ Vincent, N Noll, RB AF Phipps, Sean Buckholdt, Kelly E. Fernandez, Laly Wiener, Lori Kupst, Mary Jo Madan-Swain, Avi Mullins, Larry Robert, Rhonda Sahler, Olle Jane Vincent, Nicole Noll, Robert B. TI Pediatric oncologists' practices of prescribing selective serotonin reuptake inhibitors (SSRIs) for children and adolescents with cancer: A multi-site study SO PEDIATRIC BLOOD & CANCER LA English DT Article DE antidepressants; depression; FDA; psychology; supportive care ID DEPRESSIVE SYMPTOMS; ADAPTIVE STYLE; METAANALYSIS; PREVALENCE; MEDICATION AB Objective To survey pediatric oncologists regarding prescription of selective serotonin reuptake inhibitors (SSRIs) and related medications for the treatment of depression and anxiety disorders in children with cancer. Specifically, we sought to determine (a) how frequently pediatric oncologists prescribed SSRIs and what were the most commonly prescribed agents; (b) how decisions were made to prescribe, particularly whether mental health professionals were consulted; (c) how patients were monitored while on the agents; and (d) how the FDA black box warning has affected prescribing practices. Method. Oncologists from nine children's cancer centers (N = 151) from across the U.S. were surveyed, responding to either on- line or paper versions of a questionnaire developed for this study. Results. A majority of oncologists (71%) reported prescribing SSRIs for their patients. Oncologists reported difficulties differentiating symptoms of depression from aspects of cancer treatment. Mental health practitioners are consulted occasionally but not routinely, and oncologists reported a need for increased mental health resources. Approximately half of oncologists (51%) reported that the FDA black box warning had not affected their practice. In addition, only 28% reported monitoring patients on SSRIs at FDA recommended intervals, and only 9% indicated assessing for suicidality. Conclusions. Prescription of SSRIs is a common practice of pediatric oncologists, often without consultation with mental health professionals. Post- prescription monitoring appears to be suboptimal, and does not follow FDA guidelines. Pediatr Blood Cancer. Pediatr Blood Cancer 2012: 58: 210- 215. (C) 2011 Wiley Periodicals, Inc. C1 [Phipps, Sean; Buckholdt, Kelly E.] St Jude Childrens Res Hosp, Dept Behav Med, Memphis, TN 38105 USA. [Fernandez, Laly; Noll, Robert B.] Childrens Hosp Pittsburgh, Child Dev Unit, Pittsburgh, PA 15213 USA. [Wiener, Lori] NCI, Bethesda, MD 20892 USA. [Kupst, Mary Jo] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Madan-Swain, Avi] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. [Mullins, Larry] Oklahoma State Univ, Dept Psychol, Stillwater, OK 74078 USA. [Robert, Rhonda] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Sahler, Olle Jane] Univ Rochester, Med Ctr, Golisano Childrens Hosp, Rochester, NY 14642 USA. [Vincent, Nicole] Childrens Hosp Orange Cty, Orange, CA 92668 USA. RP Phipps, S (reprint author), St Jude Childrens Res Hosp, Dept Psychol, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM sean.phipps@stjude.org NR 21 TC 4 Z9 4 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2012 VL 58 IS 2 BP 210 EP 215 DI 10.1002/pbc.22788 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 864RZ UT WOS:000298259000010 PM 21284076 ER PT J AU Wilson, ST Stanley, B Brent, DA Oquendo, MA Huang, YY Haghighi, F Hodgkinson, CA Mann, JJ AF Wilson, Scott T. Stanley, Barbara Brent, David A. Oquendo, Maria A. Huang, Yung-yu Haghighi, Fatemeh Hodgkinson, Colin A. Mann, J. John TI Interaction between tryptophan hydroxylase I polymorphisms and childhood abuse is associated with increased risk for borderline personality disorder in adulthood SO PSYCHIATRIC GENETICS LA English DT Article DE A218C; borderline personality disorder; childhood abuse; G-6526A; suicide; tryptophan hydroxylase I ID POSTTRAUMATIC-STRESS-DISORDER; DELIBERATE SELF-HARM; DORSAL RAPHE NUCLEUS; A218C POLYMORPHISM; SUICIDAL-BEHAVIOR; COMMUNITY SAMPLE; MESSENGER-RNA; TPH GENE; SEROTONIN; PSYCHOPATHOLOGY AB Introduction Borderline personality disorder (BPD) is a severe disorder with high morbidity and mortality, but unknown etiology. Childhood abuse has been proposed as an etiological factor, but the mechanism by which an abuse history could influence the risk for BPD has not been determined. The aim of this study was to determine whether the tryptophan hydroxylase 1 (TPH1) gene is related to BPD in a clinical sample, and whether TPH1 genotypes or haplotypes moderate the relationship between abuse history and BPD. Methods Three hundred and ninety-eight patients diagnosed with mood disorders were genotyped for TPH1 G-6526A promoter polymorphism (rs4537731) and the A218C intron 7 polymorphism (rs1800532) and a set of ancestry informative markers, assessed for Diagnostic and Statistical Manual of Mental Disorders, 4th edition diagnoses, and assessed for a history of physical and sexual abuse. Results Patients with a diagnosis of BPD were more likely to be risk allele carriers (A alleles at both loci) than the non-BPD group. Logistic regression analysis predicting BPD diagnosis with both single-nucleotide polymorphisms and haplotypes showed significant interaction effects between genotype and abuse history. Poisson regression predicting the number of BPD diagnostic criteria met with the same predictor set also included a significant interaction term. Risk allele carriers with a history of abuse had an increased likelihood of a BPD diagnosis. Conclusion Variation in TPH1may increase risk for developing BPD as a result of childhood abuse. Elements of BPD pathology may be due in part to a genetically influenced serotonergic dysfunction, which in turn may lead to a differential response to environmental stressors. Psychiatr Genet 22: 15-24 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Wilson, Scott T.] New York State Psychiat Inst & Hosp, Dept Mol Imaging & Neuropathol, Unit 42, Div Mol Imaging & Neuropathol, New York, NY 10032 USA. [Wilson, Scott T.; Stanley, Barbara; Oquendo, Maria A.; Huang, Yung-yu; Mann, J. John] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Stanley, Barbara] CUNY, John Jay Coll, Dept Psychol, New York, NY 10021 USA. [Brent, David A.] Univ Pittsburgh, Med Ctr, Dept Psychiat, New York, NY USA. [Hodgkinson, Colin A.] NIAAA, Neurogenet Lab, New York, NY USA. RP Wilson, ST (reprint author), New York State Psychiat Inst & Hosp, Dept Mol Imaging & Neuropathol, Unit 42, Div Mol Imaging & Neuropathol, 1051 Riverside Dr, New York, NY 10032 USA. EM stw16@columbia.edu RI Stanley, Barbara/J-8736-2013 FU National Institute of Mental Health [MH 48514, MH62185, MH59710, MH61017, MH62665]; National Institute on Alcohol Abuse and Alcoholism [AA15630] FX This study was funded in part by grants from the National Institute of Mental Health (MH 48514, MH62185, MH59710, MH61017, and MH62665) and the National Institute on Alcohol Abuse and Alcoholism (AA15630). NR 62 TC 10 Z9 10 U1 2 U2 10 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 15 EP 24 DI 10.1097/YPG.0b013e32834c0c4c PG 10 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 866JN UT WOS:000298376800002 PM 21989108 ER PT J AU Feng, Y He, XZ Yang, YL Chao, DM Lazarus, LH Xia, Y AF Feng, Yuan He, Xiaozhou Yang, Yilin Chao, Dongman Lazarus, Lawrence H. Xia, Ying TI Current Research on Opioid Receptor Function SO CURRENT DRUG TARGETS LA English DT Article DE Opioids; opioid receptors; neurotransmitters; function; brain; heart; lung; ionic homeostasis; neuroprotection; hibernation; pain; hypoxia; ischemia ID MESSENGER-RNA EXPRESSION; INTRACELLULAR FREE CALCIUM; DIET-INDUCED OBESITY; GUINEA-PIG HEART; PROTEIN-KINASE-C; HIPPOCAMPAL HYPOXIA/HYPOGLYCEMIA MODEL; NOCICEPTIN/ORPHANIN FQ RECEPTOR; MORPHINE-INDUCED ANALGESIA; ACUTE CEREBRAL-ISCHEMIA; TEMPORAL-LOBE EPILEPSY AB The use of opioid analgesics has a long history in clinical settings, although the comprehensive action of opioid receptors is still less understood. Nonetheless, recent studies have generated fresh insights into opioid receptor-mediated functions and their underlying mechanisms. Three major opioid receptors (mu-opioid receptor, MOR; delta-opioid receptor, DOR; and kappa-opioid receptor, KOR) have been cloned in many species. Each opioid receptor is functionally sub-classified into several pharmacological subtypes, although, specific gene corresponding each of these receptor subtypes is still unidentified as only a single gene has been isolated for each opioid receptor. In addition to pain modulation and addiction, opioid receptors are widely involved in various physiological and pathophysiological activities, including the regulation of membrane ionic homeostasis, cell proliferation, emotional response, epileptic seizures, immune function, feeding, obesity, respiratory and cardiovascular control as well as some neurodegenerative disorders. In some species, they play an essential role in hibernation. One of the most exciting findings of the past decade is the opioid-receptor, especially DOR, mediated neuroprotection and cardioprotection. The upregulation of DOR expression and DOR activation increase the neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers (depending on stress duration and severity) different mechanisms at multiple levels to preserve neuronal survival, including the stabilization of homeostasis and increased pro-survival signaling (e.g., PKC-ERK-Bcl 2) and anti-oxidative capacity. In the heart, PKC and KATP channels are involved in the opioid receptor-mediated cardioprotection. The DOR-mediated neuroprotection and cardioprotection have the potential to significantly alter the clinical pharmacology in terms of prevention and treatment of life-threatening conditions like stroke and myocardial infarction. The main purpose of this article is to review the recent work done on opioids and their receptor functions. It shall provide an informative reference for better understanding the opioid system and further elucidation of the opioid receptor function from a physiological and pharmacological point of view. C1 [Feng, Yuan; Chao, Dongman; Xia, Ying] Yale Univ, Sch Med, New Haven, CT USA. [He, Xiaozhou; Yang, Yilin] Soochow Univ, Clin Coll 3, Changzhou, Jiangsu, Peoples R China. [Chao, Dongman; Xia, Ying] Univ Texas Houston, Med Sch Houston, Houston, TX 77030 USA. [Lazarus, Lawrence H.] NIEHS, Res Triangle Pk, NC 27709 USA. [Feng, Yuan] Nanjing Med Univ, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China. RP Xia, Y (reprint author), Univ Texas Houston, Med Sch Houston, 6431 Fannin St, Houston, TX 77030 USA. EM ying.xia@uth.tmc.edu FU NIH [HD-34852, AT-004422]; Vivian L Smith Neurologic Foundation; Intramural Research Program of the NIH; NIEHS FX This work was supported by NIH (HD-34852 and AT-004422), Vivian L Smith Neurologic Foundation and in part by the Intramural Research Program of the NIH and NIEHS. NR 314 TC 69 Z9 78 U1 2 U2 28 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD FEB PY 2012 VL 13 IS 2 BP 230 EP 246 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 204ND UT WOS:000323371100009 PM 22204322 ER PT J AU Hoffert, JD Pisitkun, T Saeed, F Song, JH Chou, CL Knepper, MA AF Hoffert, Jason D. Pisitkun, Trairak Saeed, Fahad Song, Jae H. Chou, Chung-Lin Knepper, Mark A. TI Dynamics of the G Protein-coupled Vasopressin V2 Receptor Signaling Network Revealed by Quantitative Phosphoproteomics SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID MEDULLARY COLLECTING DUCT; RENAL PRINCIPAL CELLS; BETA-CATENIN; KINASE-A; IN-VIVO; AQUAPORIN-2 TRAFFICKING; LC-MS/MS; PHOSPHORYLATION; IDENTIFICATION; ACTIVATION AB G protein-coupled receptors (GPCRs) regulate diverse physiological processes, and many human diseases are due to defects in GPCR signaling. To identify the dynamic response of a signaling network downstream from a prototypical G(s)-coupled GPCR, the vasopressin V2 receptor, we have carried out multireplicate, quantitative phosphoproteomics with iTRAQ labeling at four time points following vasopressin exposure at a physiological concentration in cells isolated from rat kidney. A total of 12,167 phosphopeptides were identified from 2,783 proteins, with 273 changing significantly in abundance with vasopressin. Two-dimensional clustering of phosphopeptide time courses and Gene Ontology terms revealed that ligand binding to the V2 receptor affects more than simply the canonical cyclic adenosine monophosphate-protein kinase A and arrestin pathways under physiological conditions. The regulated proteins included key components of actin cytoskeleton remodeling, cell-cell adhesion, mitogen-activated protein kinase signaling, Wnt/beta-catenin signaling, and apoptosis pathways. These data suggest that vasopressin can regulate an array of cellular functions well beyond its classical role in regulating water and solute transport. These results greatly expand the current view of GPCR signaling in a physiological context and shed new light on potential roles for this signaling network in disorders such as polycystic kidney disease. Finally, we provide an online resource of physiologically regulated phosphorylation sites with dynamic quantitative data (http://helixweb.nih.gov/ESBL/Database/TiPD/index.html). Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.014613, 1-15, 2012. C1 [Hoffert, Jason D.; Pisitkun, Trairak; Saeed, Fahad; Song, Jae H.; Chou, Chung-Lin; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hoffert, JD (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr, Bethesda, MD 20892 USA. EM hoffertj@nhlbi.nih.gov RI Saeed, Fahad/D-1545-2013; OI Pisitkun, Trairak/0000-0001-6677-2271 FU National Institutes of Health, NHLBI [ZO1-HL001285] FX This work was supported by the National Institutes of Health, NHLBI intramural budget Grant ZO1-HL001285. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 79 TC 9 Z9 9 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD FEB PY 2012 VL 11 IS 2 AR M111.014613 DI 10.1074/mcp.M111.014613 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 889EL UT WOS:000300056200027 PM 22108457 ER PT J AU Wilke, M Dechent, P Schmidt-Samoa, C AF Wilke, Melanie Dechent, Peter Schmidt-Samoa, Carsten TI Experimental models for spatials Neglect (Studies in humans and non-humans Primates) SO NEUROFORUM LA German DT Article DE spatial neglect; pulvinar; eye movements; visual awareness; attention AB Spatial neglect is a debilitating neuropsychological disorder that is characterized by an impaired or lost ability to explore the space contralateral to the lesion and to react to stimuli presented on this side. Lesion sites that have been implicated in spatial neglect form a widely distributed network consisting of a number of cortical (i.e. fronto-parietal) and subcortical (i.e. thalamic) areas which are in healthy individuals activated during attentional and visuomotor tasks. While a detailed understanding of the brain circuits and mechanisms involved in spatial neglect is a prerequisite for the development of effective therapies, this has proven to be difficult in human patients, partly due to the extent and variability between lesion sites. Therefore, experimental models where pre-defined brain regions can be systematically inactivated are of great advantage. Neglect models have been developed in non-human primates where it is possible to pharmacologically inactivate small brain regions and in humans by means of non-invasive stimulation/inactivation methods such as transcranial magnetic stimulation. In this paper, we discuss theories about the mechanisms of spatial neglect such as the hemispheric imbalance model and the supporting experimental evidence, with an emphasis on imaging experiments that combined lesions with measures of dynamic brain activity. C1 [Wilke, Melanie] NIMH, Bethesda, MD 20892 USA. [Wilke, Melanie] CALTECH, Pasadena, CA 91125 USA. [Wilke, Melanie] UMG, Abt Kognit Neurol, D-37075 Gottingen, Germany. [Dechent, Peter] Biomed NMR Forsch GmbH, Munich, Germany. [Dechent, Peter] UMG, Abt Kognit Neurol, Forsch Grp, D-37075 Gottingen, Germany. [Schmidt-Samoa, Carsten] UMG, D-37075 Gottingen, Germany. RP Wilke, M (reprint author), UMG, Abt Kognit Neurol, Robert Koch Str 40, D-37075 Gottingen, Germany. EM melanie.wilke@med.uni-goettingen.de; pdechen@gwdg.de; casten.schmidt-samoa@med.uni-goettingen.de NR 9 TC 0 Z9 0 U1 1 U2 2 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 0947-0875 EI 1868-856X J9 NEUROFORUM JI Neuroforum PD FEB PY 2012 VL 18 IS 1 BP 178 EP + PG 11 WC Neurosciences SC Neurosciences & Neurology GA V33SH UT WOS:000209038000002 ER PT J AU Guo, M Lu, Y Garza, JC Li, Y Chua, SC Zhang, W Lu, B Lu, XY AF Guo, M. Lu, Y. Garza, J. C. Li, Y. Chua, S. C. Zhang, W. Lu, B. Lu, X-Y TI Forebrain glutamatergic neurons mediate leptin action on depression-like behaviors and synaptic depression SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE behavioral depression; GluN2B subunit; glutamatergic neurons; leptin receptor; NMDA receptors; synaptic depression ID LONG-TERM DEPRESSION; PITUITARY-ADRENOCORTICAL AXIS; D-ASPARTATE ANTAGONIST; TAIL SUSPENSION TEST; IN-VIVO; MOOD DISORDERS; RECEPTOR GENE; ANIMAL-MODEL; ANTIDEPRESSANT ACTIVITY; HIPPOCAMPAL FUNCTION AB The glutamatergic system has been implicated in the pathophysiology of depression and the mechanism of action of antidepressants. Leptin, an adipocyte-derived hormone, has antidepressant-like properties. However, the functional role of leptin receptor (Lepr) signaling in glutamatergic neurons remains to be elucidated. In this study, we generated conditional knockout mice in which the long form of Lepr was ablated selectively in glutamatergic neurons located in the forebrain structures, including the hippocampus and prefrontal cortex (Lepr cKO). Lepr cKO mice exhibit normal growth and body weight. Behavioral characterization of Lepr cKO mice reveals depression-like behavioral deficits, including anhedonia, behavioral despair, enhanced learned helplessness and social withdrawal, with no evident signs of anxiety. In addition, loss of Lepr in forebrain glutamatergic neurons facilitates N-methyl-D-aspartate (NMDA)-induced hippocampal long-term synaptic depression (LTD), whereas conventional LTD or long-term potentiation (LTP) was not affected. The facilitated LTD induction requires activation of the NMDA receptor GluN2B (NR2B) subunit as it was completely blocked by a selective GluN2B antagonist. Moreover, Lepr cKO mice are highly sensitive to the antidepressant-like behavioral effects of the GluN2B antagonist but resistant to leptin. These results support important roles for Lepr signaling in glutamatergic neurons in regulating depression-related behaviors and modulating excitatory synaptic strength, suggesting a possible association between synaptic depression and behavioral manifestation of behavioral depression. Translational Psychiatry (2012) 2, e83; doi:10.1038/tp.2012.9; published online 21 February 2012 C1 [Guo, M.; Garza, J. C.; Zhang, W.; Lu, X-Y] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Lu, Y.; Lu, B.] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Li, Y.] Univ Alabama Birmingham, Sch Med, Dept Neurol, Birmingham, AL USA. [Chua, S. C.] Albert Einstein Coll Med, Dept Med, New York, NY USA. [Chua, S. C.] Albert Einstein Coll Med, Dept Neurosci, New York, NY USA. [Lu, B.] GlaxoSmithKline, R&D China, Shanghai 201203, Peoples R China. [Lu, X-Y] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. RP Lu, XY (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM bai.b.lu@gsk.com; lux3@uthscsa.edu RI Li, Yuqing/G-1596-2011; Lu, Xin-Yun/M-8657-2016 OI Li, Yuqing/0000-0003-1211-5529; FU NIH [NIMH 076929, NIMH 073844]; NRSA [NIMH 83442]; NICHD; NIMH FX This work was supported by the NIH Grants NIMH 076929 and NIMH 073844 (to X-YL), the NRSA predoctoral fellowship award NIMH 83442 (to JCG) and funds from intramural research programs of the NICHD and NIMH (to BL). NR 113 TC 30 Z9 31 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD FEB PY 2012 VL 2 AR e83 DI 10.1038/tp.2012.9 PG 15 WC Psychiatry SC Psychiatry GA 104JW UT WOS:000315989800008 PM 22408745 ER PT J AU Ambatipudi, S Gerstung, M Pandey, M Samant, T Patil, A Kane, S Desai, RS Schaffer, AA Beerenwinkel, N Mahimkar, MB AF Ambatipudi, Srikant Gerstung, Moritz Pandey, Manishkumar Samant, Tanuja Patil, Asawari Kane, Shubhada Desai, Rajiv S. Schaeffer, Alejandro A. Beerenwinkel, Niko Mahimkar, Manoj B. TI Genome-wide expression and copy number analysis identifies driver genes in gingivobuccal cancers SO GENES CHROMOSOMES & CANCER LA English DT Article ID SQUAMOUS-CELL CARCINOMA; LYMPH-NODE METASTASIS; ORAL-CANCER; MICROARRAY ANALYSIS; TUMOR-ANGIOGENESIS; DNA AMPLIFICATION; CDNA MICROARRAY; DOWN-REGULATION; POOR SURVIVAL; TONGUE CANCER AB The molecular mechanisms contributing to the development and progression of gingivobuccal complex (GBC) cancersa sub-site of oral cancer, comprising the buccal mucosa, the gingivobuccal sulcus, the lower gingival region, and the retromolar trigoneremain poorly understood. Identifying the GBC cancer-related gene expression signature and the driver genes residing on the altered chromosomal regions is critical for understanding the molecular basis of its pathogenesis. Genome-wide expression profiling of 27 GBC cancers with known chromosomal alterations was performed to reveal differentially expressed genes. Putative driver genes were identified by integrating copy number and gene expression data. A total of 315 genes were found differentially expressed (P = 0.05, logFC > 2.0) of which 11 genes were validated by real-time quantitative reverse transcriptase-PCR (qRT-PCR) in tumors (n = 57) and normal GBC tissues (n = 18). Overexpression of LY6K, in chromosome band 8q24.3, was validated by immunohistochemical (IHC) analysis. We found that 78.5% (2,417/3,079) of the genes located in regions of recurrent chromosomal alterations show copy number dependent expression indicating that copy number alteration has a direct effect on global gene expression. The integrative analysis revealed BIRC3 in 11q22.2 as a candidate driver gene associated with poor clinical outcome. Our study identified previously unreported differentially expressed genes in a homogeneous subtype of oral cancer and the candidate driver genes that may contribute to the development and progression of the disease. (C) 2011 Wiley Periodicals, Inc. C1 [Ambatipudi, Srikant; Pandey, Manishkumar; Samant, Tanuja; Mahimkar, Manoj B.] TMC, ACTREC, CRI, Kharghar 410210, Navi Mumbai, India. [Gerstung, Moritz; Beerenwinkel, Niko] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland. [Gerstung, Moritz; Beerenwinkel, Niko] Swiss Inst Bioinformat, CH-4058 Basel, Switzerland. [Patil, Asawari; Kane, Shubhada] Tata Mem Hosp, TMC, Dept Pathol, Bombay 400012, Maharashtra, India. [Desai, Rajiv S.] Nair Hosp Dent Coll, Dept Oral Pathol & Microbiol, Bombay 400008, Maharashtra, India. [Schaeffer, Alejandro A.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, DHHS, Bethesda, MD 20894 USA. RP Mahimkar, MB (reprint author), TMC, ACTREC, CRI, Kharghar 410210, Navi Mumbai, India. EM mmahimkar@actrec.gov.in RI Schaffer, Alejandro/F-2902-2012; Ambatipudi, Srikant/J-4648-2012; OI Gerstung, Moritz/0000-0001-6709-963X; AMBATIPUDI, SRIKANT/0000-0003-3102-3603 FU Lady Tata Memorial Trust, Mumbai; Council of Scientific and Industrial Research [27(0207)/09/EMR-II]; National Institutes of Health, NLM; SystemsX.ch [2009/024] FX Supported by: Lady Tata Memorial Trust, Mumbai, and the Council of Scientific and Industrial Research, Grant number: 27(0207)/09/EMR-II; Intramural Research program of the National Institutes of Health, NLM; SystemsX.ch, Grant number: 2009/024. NR 61 TC 17 Z9 18 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD FEB PY 2012 VL 51 IS 2 BP 161 EP 173 DI 10.1002/gcc.20940 PG 13 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 857QS UT WOS:000297734400006 PM 22072328 ER PT J AU Follmann, D Proschan, M AF Follmann, Dean Proschan, Michael TI A test of location for exchangeable multivariate normal data with unknown correlation SO JOURNAL OF MULTIVARIATE ANALYSIS LA English DT Article DE Confidence interval; Within cluster resampling; Likelihood ratio test ID MULTIPLE END-POINTS; P-VALUES AB We consider the problem of testing whether the common mean of a single n-vector of multivariate normal random variables with known variance and unknown common correlation rho is zero. We derive the standardized likelihood ratio test for known rho and explore different ways of proceeding with rho unknown. We evaluate the performance of the standardized statistic where rho is replaced with an estimate of rho and determine the critical value c(n) that controls the type I error rate for the least favorable rho in [0,1]. The constant c(n) increases with n and this procedure has pathological behavior if rho depends on n and rho(n) converges to zero at a certain rate. As an alternate approach, we replace rho with the upper limit of a (1 - beta(n)) confidence interval chosen so that c(n) = c for all n. We determine beta(n) so that the type I error rate is exactly controlled for all rho in [0,1]. We also investigate a simpler approach where we bound the type I error rate. The former method performs well for all n while the less powerful bound method may be a useful in some settings as a simple approach. The proposed tests can be used in different applications, including within-cluster resampling and combining exchangeable p-values. Published by Elsevier Inc. C1 [Follmann, Dean; Proschan, Michael] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Follmann, D (reprint author), NIAID, Biostat Res Branch, 6700B Rockledge Dr,MSC 7609, Bethesda, MD 20892 USA. EM dfollmann@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 8 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0047-259X J9 J MULTIVARIATE ANAL JI J. Multivar. Anal. PD FEB PY 2012 VL 104 IS 1 BP 115 EP 125 DI 10.1016/j.jmva.2011.07.003 PG 11 WC Statistics & Probability SC Mathematics GA 826KR UT WOS:000295353500008 PM 22125347 ER PT J AU Tyagi, M Thangudu, RR Zhang, DC Bryant, SH Madej, T Panchenko, AR AF Tyagi, Manoj Thangudu, Ratna R. Zhang, Dachuan Bryant, Stephen H. Madej, Thomas Panchenko, Anna R. TI Homology Inference of Protein-Protein Interactions via Conserved Binding Sites SO PLOS ONE LA English DT Article ID INTERACTION NETWORKS; PREDICTION; SEQUENCE; CLASSIFICATION; ANNOTATION; DIVERGENCE; INTEROLOGS; COMPLEXES; DATABASE; SERVER AB The coverage and reliability of protein-protein interactions determined by high-throughput experiments still needs to be improved, especially for higher organisms, therefore the question persists, how interactions can be verified and predicted by computational approaches using available data on protein structural complexes. Recently we developed an approach called IBIS (Inferred Biomolecular Interaction Server) to predict and annotate protein-protein binding sites and interaction partners, which is based on the assumption that the structural location and sequence patterns of protein-protein binding sites are conserved between close homologs. In this study first we confirmed high accuracy of our method and found that its accuracy depends critically on the usage of all available data on structures of homologous complexes, compared to the approaches where only a non-redundant set of complexes is employed. Second we showed that there exists a trade-off between specificity and sensitivity if we employ in the prediction only evolutionarily conserved binding site clusters or clusters supported by only one observation (singletons). Finally we addressed the question of identifying the biologically relevant interactions using the homology inference approach and demonstrated that a large majority of crystal packing interactions can be correctly identified and filtered by our algorithm. At the same time, about half of biological interfaces that are not present in the protein crystallographic asymmetric unit can be reconstructed by IBIS from homologous complexes without the prior knowledge of crystal parameters of the query protein. C1 [Tyagi, Manoj; Thangudu, Ratna R.; Zhang, Dachuan; Bryant, Stephen H.; Madej, Thomas; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Tyagi, M (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM madej@ncbi.nlm.nih.gov; panch@ncbi.nlm.nih.gov RI Tyagi, Manoj/K-8438-2014 FU National Institutes of Health/Department of Health and Human Services of the National Library of Medicine FX This work was supported by the National Institutes of Health/Department of Health and Human Services Intramural Research program of the National Library of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 12 Z9 12 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 31 PY 2012 VL 7 IS 1 AR e28896 DI 10.1371/journal.pone.0028896 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 912BY UT WOS:000301770700003 PM 22303436 ER PT J AU Todd, CA Greene, KM Yu, XS Ozaki, DA Gao, HM Huang, YD Wang, M Li, G Brown, R Wood, B D'Souza, MP Gilbert, P Montefiori, DC Sarzotti-Kelsoe, M AF Todd, Christopher A. Greene, Kelli M. Yu, Xuesong Ozaki, Daniel A. Gao, Hongmei Huang, Yunda Wang, Maggie Li, Gary Brown, Ronald Wood, Blake D'Souza, M. Patricia Gilbert, Peter Montefiori, David C. Sarzotti-Kelsoe, Marcella TI Development and implementation of an international proficiency testing program for a neutralizing antibody assay for HIV-1 in TZM-bl cells SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Neutralizing; Antibody; Assay; Proficiency; HIV; TZM-bl ID IMMUNODEFICIENCY-VIRUS TYPE-1; FUSION INHIBITOR T-20; ENV CLONES; INFECTIONS; NETWORK; CCR5 AB Recent advances in assay technology have led to major improvements in how HIV-1 neutralizing antibodies are measured. A luciferase reporter gene assay performed in TZM-bl (JC53bl-13) cells has been optimized and validated. Because this assay has been adopted by multiple laboratories worldwide, an external proficiency testing program was developed to ensure data equivalency across laboratories performing this neutralizing antibody assay for HIV/AIDS vaccine clinical trials. The program was optimized by conducting three independent rounds of testing, with an increased level of stringency from the first to third round. Results from the participating domestic and international laboratories improved each round as factors that contributed to interassay variability were identified and minimized. Key contributors to increased agreement were experience among laboratories and standardization of reagents. A statistical qualification rule was developed using a simulation procedure based on the three optimization rounds of testing, where a laboratory qualifies if at least 25 of the 30 ID50 values lie within the acceptance ranges. This ensures no more than a 20% risk that a participating laboratory fails to qualify when it should, as defined by the simulation procedure. Five experienced reference laboratories were identified and tested a series of standardized reagents to derive the acceptance ranges for pass-fail criteria. This Standardized Proficiency Testing Program is the first available for the evaluation and documentation of assay equivalency for laboratories performing HIV-1 neutralizing antibody assays and may provide guidance for the development of future proficiency testing programs for other assay platforms. (C) 2011 Elsevier B.V. All rights reserved. C1 [Todd, Christopher A.; Greene, Kelli M.; Ozaki, Daniel A.; Gao, Hongmei; Montefiori, David C.; Sarzotti-Kelsoe, Marcella] Duke Univ, Med Ctr, Durham, NC 27705 USA. [Yu, Xuesong; Huang, Yunda; Wang, Maggie; Wood, Blake; Gilbert, Peter] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. [Li, Gary; Brown, Ronald] Qual Biol Inc, Gaithersburg, MD USA. [D'Souza, M. Patricia] NIAID, NIH, Div Aids, Bethesda, MD 20892 USA. RP Sarzotti-Kelsoe, M (reprint author), Duke Univ, Med Ctr, 2812 Erwin Rd,Ste 301,Erwin Terrace 2, Durham, NC 27705 USA. EM chris.todd@duke.edu; kelli.greene@duke.edu; xyu@scharp.org; daniel.ozaki@dm.duke.edu; hongmei.gao@duke.edu; yunda@scharp.org; maggie@fhcrc.org; lig@qualitybiological.com; brownr@qualitybiological.com; geebeewood@gmail.com; pdsouza@niaid.nih.gov; pgilbert@scharp.org; monte@duke.edu; marcella.sarzottikelsoe@dm.duke.edu FU Bill & Melinda Gates Foundation [38619]; Collaboration for AIDS Vaccine Discovery/Vaccine Immunology Statistical Center [38744]; National Institutes of Health [AI30034]; NIH/NIAID, Quality Biological, Inc. FX This program is jointly supported by the Bill & Melinda Gates Foundation's Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody Vaccine Immune Monitoring Consortium, grant number 38619, Collaboration for AIDS Vaccine Discovery/Vaccine Immunology Statistical Center, grant number 38744, National Institutes of Health grant AI30034, and the NIH/NIAID Reagent Resource Support Program for AIDS Vaccine Development, Quality Biological, Inc., Gaithersburg, MD. This paper was submitted by one author in her capacity as an employee of NIH, but the views expressed in this paper do not necessarily represent those of NIH. We also thank all of the laboratories that participated in the development of this program. NR 17 TC 18 Z9 18 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JAN 31 PY 2012 VL 375 IS 1-2 BP 57 EP 67 DI 10.1016/j.jim.2011.09.007 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 900TO UT WOS:000300913300008 PM 21968254 ER PT J AU Weiss, GE Ndungu, FM McKittrick, N Li, SP Kimani, D Crompton, PD Marsh, K Pierce, SK AF Weiss, Greta E. Ndungu, Francis M. McKittrick, Noah Li, Shanping Kimani, Domtila Crompton, Peter D. Marsh, Kevin Pierce, Susan K. TI High efficiency human memory B cell assay and its application to studying Plasmodium falciparum-specific memory B cells in natural infections SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Memory B cells; B cell ELISPOT; Plasmodium falciparum; Malaria ID MALARIA-ENDEMIC AREA; PLASMA-CELLS; DIFFERENTIATION; INDIVIDUALS; ANTIGENS; IMMUNITY AB Memory B cells (MBCs) are a key component of long term humoral immunity to many human infectious diseases. Despite their importance, we know little about the generation or maintenance of antigen-(Ag)-specific MBCs in humans in response to infection. A frequently employed method for quantifying Ag-specific MBCs in human peripheral blood (Crotty et al., 2004) relies on the ability of MBCs but not naive B cells to differentiate into antibody secreting cells (ASCs) in response to polyclonal activators and Toll-like receptor agonists in vitro and the measurement of Ag-specific ASCs by ELISPOT assays. Here we report on studies to optimize the efficiency of this ELISPOT-based assay and to apply this assay to the detection of Plasmodium falciparum (PP-specific MBCs in adults living in a malaria endemic area where immunity to Pf is acquired through natural infection. We show that the addition of IL-10 to in vitro cultures of human peripheral blood mononuclear cells increased the efficiency of the assay from 10% to over 90% without increasing the ASC burst size and without any substantial increase in background from naive B cells or plasma cells (PCs). Using this assay we were able to quantify the frequency of Pf-specific MBCs in peripheral blood of adults living in a malaria endemic area. Thus, this highly efficient assay appears to be well suited to field studies of the generation and maintenance of MBCs where the volumes of blood obtainable are often limiting. (C) 2011 Elsevier B.V. All rights reserved. C1 [Weiss, Greta E.; Li, Shanping; Crompton, Peter D.; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Ndungu, Francis M.; Kimani, Domtila; Marsh, Kevin] Kenya Govt Med Res Ctr, Ctr Geog Med Res Coast, Kilifi 80108, Kenya. [McKittrick, Noah] Univ Penn, Philadelphia, PA 19104 USA. RP Weiss, GE (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr,Room 213, Rockville, MD 20852 USA. EM weiss@burnet.edu.au RI Crompton, Peter/N-1130-2016; OI McKittrick, Noah/0000-0001-6277-2733 FU Intramural NIH HHS [ZIA AI000949-06]; Wellcome Trust [092654] NR 20 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JAN 31 PY 2012 VL 375 IS 1-2 BP 68 EP 74 DI 10.1016/j.jim.2011.09.006 PG 7 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 900TO UT WOS:000300913300009 PM 21963949 ER PT J AU Memon, SA Sportes, C Flomerfelt, FA Gress, RE Hakim, FT AF Memon, Sarfraz A. Sportes, Claude Flomerfelt, Francis A. Gress, Ronald E. Hakim, Frances T. TI Quantitative analysis of T cell receptor diversity in clinical samples of human peripheral blood SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE TCR V beta CDR3 repertoire diversity in human peripheral blood; Spectratype; Immune reconstitution; Hematopoietic stem cell transplantation ID TUMOR-INFILTRATING LYMPHOCYTES; MULTIPLE-SCLEROSIS PATIENTS; V-BETA REPERTOIRE; MARROW-TRANSPLANTATION; ANTIRETROVIRAL THERAPY; IMMUNE RECONSTITUTION; STATISTICAL-ANALYSIS; SPECTRATYPE ANALYSIS; CLONAL DOMINANCE; THYMIC FUNCTION AB The analysis of T cell receptor diversity provides a clinically relevant and sensitive marker of repertoire loss, gain, or skewing. Spectratyping is a broadly utilized technique to measure global TCR diversity by the analysis of the lengths of CDR3 fragments in each V beta family. However the common use of large numbers of T cells to obtain a global view of TCR V beta CDR3 diversity has restricted spectratyping analyses when limited T-cell numbers are available in clinical setting, such as following transplant regimens. We here demonstrate that one hundred thousand T cells are sufficient to obtain a robust, highly reproducible measure of the global TCR V beta repertoire diversity among twenty V beta families in human peripheral blood. We also show that use of lower cell number results not in a dwindling of observed diversity but rather in non-reproducible patterns in replicate spectratypes. Finally, we report here a simple to use but sensitive method to quantify repertoire divergence in patient samples by comparison to a standard repertoire profile we generated from fifteen normal donors. We provide examples using this method to statistically evaluate the changes in the global TCR V beta repertoire diversity that may take place during T subset immune reconstitution after hematopoietic stem cell transplantation or after immune modulating therapies. Published by Elsevier B.V. C1 [Memon, Sarfraz A.; Sportes, Claude; Flomerfelt, Francis A.; Gress, Ronald E.; Hakim, Frances T.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Memon, SA (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,CRC Room 3-3288, Bethesda, MD 20892 USA. EM memons@mail.nih.gov RI Memon, Sarfraz/E-1198-2013; OI Memon, Sarfraz/0000-0002-0164-9739 FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 51 TC 9 Z9 9 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JAN 31 PY 2012 VL 375 IS 1-2 BP 84 EP 92 DI 10.1016/j.jim.2011.09.012 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 900TO UT WOS:000300913300011 PM 21986106 ER PT J AU Oliveira, TY Resch, W Jankovic, M Casellas, R Nussenzweig, MC Klein, IA AF Oliveira, Thiago Y. Resch, Wolfgang Jankovic, Mila Casellas, Rafael Nussenzweig, Michel C. Klein, Isaac A. TI Translocation capture sequencing: A method for high throughput mapping of chromosomal rearrangements SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Chromosomal translocations; Genomic instability; Activation-induced cytidine deaminase; B lymphocytes; Lymphoma ID CLASS-SWITCH RECOMBINATION; CYTIDINE DEAMINASE AID; DOUBLE-STRAND BREAKS; SOMATIC HYPERMUTATION; B-LYMPHOCYTES; CELL LYMPHOMAS; IG GENES; C-MYC; ACTIVATION; DNA AB Chromosomal translocations require formation and joining of DNA double strand breaks (DSBs). These events disrupt the integrity of the genome and are involved in producing leukemias, lymphomas and sarcomas. Translocations are frequent, clonal and recurrent in mature B cell lymphomas, which bear a particularly high DNA damage burden by virtue of activation-induced cytidine deaminase (AID) expression. Despite the ubiquity of genomic rearrangements, the forces that underlie their genesis are not well understood. Here, we provide a detailed description of a new method for studying these events, translocation capture sequencing (TC-Seq). TC-Seq provides the means to document chromosomal rearrangements genome-wide in primary cells, and to discover recombination hotspots. Demonstrating its effectiveness, we successfully estimate the frequency of c-myc/IgH translocations in primary B cells, and identify hotspots of AID-mediated recombination. Furthermore. TC-Seq can be adapted to generate genome-wide rearrangement maps in any cell type and under any condition. (C) 2011 Elsevier B.V. All rights reserved. C1 [Oliveira, Thiago Y.; Jankovic, Mila; Nussenzweig, Michel C.; Klein, Isaac A.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. [Resch, Wolfgang; Casellas, Rafael] NIAMS, NIH, Bethesda, MD 20892 USA. [Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Oliveira, Thiago Y.] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Genet, Natl Inst Sci & Technol Stem Cells & Cell Therapy, BR-14051140 Ribeirao Preto, SP, Brazil. [Oliveira, Thiago Y.] Ctr Cell Based Therapy, BR-14051140 Ribeirao Preto, SP, Brazil. [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. RP Klein, IA (reprint author), Rockefeller Univ, Lab Mol Immunol, 1230 York Ave,Box 220, New York, NY 10065 USA. EM iklein@rockefeller.edu OI Oliveira, Thiago/0000-0002-2654-0879 FU NIH [AI037526]; NYSTEM [C023046]; The Starr Cancer Consortium; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health; NIH MSTP [GM07739] FX We thank all the members of the Nussenzweig and Casellas labs for valuable input and advice, Klara Velinzon and Svetlana Mazel for FACSorting and David Bosque and Thomas Eisenreich for animal management. We also thank Scott Dewell of the Rockefeller Genomics Resource Center and Gustavo Gutierrez of the NIAMS genome facility for high-throughput sequencing and guidance. This work was supported by NIH grant #AI037526 to M.C.N., NYSTEM #C023046, The Starr Cancer Consortium and the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. M.C.N. is an HHMI investigator. I.A.K. was supported by NIH MSTP grant GM07739, and is a Cancer Research Institute Predoctoral Fellow and a William Randolph Hearst Foundation Fellow. NR 27 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JAN 31 PY 2012 VL 375 IS 1-2 BP 176 EP 181 DI 10.1016/j.jim.2011.10.007 PG 6 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 900TO UT WOS:000300913300021 PM 22033343 ER PT J AU Gao, Y Baccarelli, A Shu, XO Ji, BT Yu, K Tarantini, L Yang, G Li, HL Hou, L Rothman, N Zheng, W Gao, YT Chow, WH AF Gao, Y. Baccarelli, A. Shu, X. O. Ji, B-T Yu, K. Tarantini, L. Yang, G. Li, H-L Hou, L. Rothman, N. Zheng, W. Gao, Y-T Chow, W-H TI Blood leukocyte Alu and LINE-1 methylation and gastric cancer risk in the Shanghai Women's Health Study SO BRITISH JOURNAL OF CANCER LA English DT Article DE gastric cancer; DNA methylation; leukocyte ID GLOBAL DNA METHYLATION; HELICOBACTER-PYLORI INFECTION; CPG ISLAND METHYLATION; GENOMIC DNA; PROMOTER METHYLATION; ENVIRONMENTAL EPIGENOMICS; DISEASE SUSCEPTIBILITY; BLADDER-CANCER; GENE PROMOTER; BREAST-CANCER AB BACKGROUND: Recent data suggest a link between blood leukocyte DNA methylation, and cancer risk. However, reports on DNA methylation from a prospective study are unavailable for gastric cancer. METHODS: We explored the association between methylation in pre-diagnostic blood leukocyte DNA and gastric cancer risk in a case-control study nested in the prospective Shanghai Women's Health Study cohort. Incident gastric cancer cases (n = 192) and matched controls (n = 384) were included in the study. Methylation of Alu and long interspersed nucleotide elements (LINE)-1 were evaluated using bisulphite pyrosequencing. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated from logistic regression adjusting for potential confounders. RESULTS: Alu methylation was inversely associated with gastric cancer risk, mainly among cases diagnosed one or more years after blood collection. After excluding cases diagnosed during the first year of follow-up, the ORs for the third, second, and first quartiles of Alu methylation compared with the highest quartile were 2.43 (1.43-4.13), 1.47 (0.85-2.57), and 2.22 (1.28-3.84), respectively. This association appeared to be modified by dietary intake, particularly isoflavone. In contrast, LINE-1 methylation levels were not associated with gastric cancer risk. CONCLUSION: Evidence from this prospective study is consistent with the hypothesis that DNA hypomethylation in blood leukocytes may be related to cancer risk, including risk of gastric cancer. British Journal of Cancer (2012) 106, 585-591. doi: 10.1038/bjc.2011.562 www.bjcancer.com Published online 15 December 2011 (C) 2012 Cancer Research UK C1 [Gao, Y.; Ji, B-T; Yu, K.; Li, H-L; Rothman, N.; Chow, W-H] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Baccarelli, A.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Shu, X. O.; Yang, G.; Zheng, W.] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA. [Tarantini, L.] Univ Milan, Mangiagalli & Regina Elena IRCCS Fdn, Maggiore Policlin Hosp, Dept Environm & Occupat Hlth,Ctr Mol & Genet Epid, I-20122 Milan, Italy. [Hou, L.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Hou, L.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Gao, Y-T] Shanghai Canc Inst, Dept Epidemiol, Shanghai 200032, Peoples R China. RP Gao, Y (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Bldg EPS,Room 7110, Bethesda, MD 20892 USA. EM gaoying@mail.nih.gov OI Baccarelli, Andrea/0000-0002-3436-0640 FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health; NIEHS [ES00002] FX This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. Dr Baccarelli is partially supported by New Investigator funding from NIEHS (ES00002). Finally, we acknowledge the study participants for donating their time and making this study possible. NR 54 TC 30 Z9 32 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 31 PY 2012 VL 106 IS 3 BP 585 EP 591 DI 10.1038/bjc.2011.562 PG 7 WC Oncology SC Oncology GA 892RC UT WOS:000300302300021 PM 22173668 ER PT J AU Blank, MM Wentzensen, N Murphy, MA Hollenbeck, A Park, Y AF Blank, M. M. Wentzensen, N. Murphy, M. A. Hollenbeck, A. Park, Y. TI Dietary fat intake and risk of ovarian cancer in the NIH-AARP Diet and Health Study SO BRITISH JOURNAL OF CANCER LA English DT Article DE dietary fat; ovarian cancer; cohort studies ID RETIRED-PERSONS DIET; AMERICAN-ASSOCIATION; LOGISTIC-REGRESSION; NATIONAL-INSTITUTES; HISTOLOGIC TYPE; COHORT; METAANALYSIS; VALIDATION AB BACKGROUND: Fat intake has been postulated to increase risk of ovarian cancer, but previous studies have reported inconsistent results. METHODS: The NIH-AARP Diet and Health Study, a large prospective cohort, assessed diet using a food frequency questionnaire at baseline in 1995-1996. During an average of 9 years of follow-up, 695 ovarian cancer cases were ascertained through the state cancer registry database. The relative risks (RRs) and 95% confidence interval (CI) were estimated using a Cox proportional hazard model. RESULTS: Women in the highest vs the lowest quintile of total fat intake had a 28% increased risk of ovarian cancer (RRQ5 (vs Q1) = 1.28, 95% CI: 1.01-1.63). Fat intake from animal sources (RRQ5 (vs Q1) = 1.30; 95% CI: 1.02-1.66), but not from plant sources, was positively associated with ovarian cancer risk. Saturated and monounsaturated fat intakes were not related to risk of ovarian cancer, but polyunsaturated fat intake showed a weak positive association. The association between total fat intake and ovarian cancer was stronger in women who were nulliparous or never used oral contraceptives. CONCLUSION: Fat intake, especially from animal sources, was related to an increased risk of ovarian cancer. The association may be modified by parity and oral contraceptive use, which warrants further investigation. British Journal of Cancer (2012) 106, 596-602. doi: 10.1038/bjc.2011.572 www.bjcancer.com Published online 5 January 2012 (C) 2012 Cancer Research UK C1 [Blank, M. M.; Wentzensen, N.; Murphy, M. A.; Park, Y.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Murphy, M. A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hollenbeck, A.] AARP, Washington, DC 20049 USA. RP Park, Y (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Rockville, MD 20852 USA. EM parkyik@mail.nih.gov OI Park, Yikyung/0000-0002-6281-489X FU Florida Department of Health (FDOH); National Cancer Institute, National Institutes of Health; NIH [5 T32 CA09001-35] FX Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University. Cancer incidence data from California were collected by the California Department of Health Services, Cancer Surveillance Section. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (FCDC) under contract with the Florida Department of Health (FDOH). Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Medical Center in New Orleans. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health and Senior Services. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations or conclusions. Cancer incidence data from Arizona were collected by the Arizona Cancer Registry, Division of Public Health Services, Arizona Department of Health Services. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services. We are indebted to the participants in the NIH-AARP Diet and Health Study for their outstanding cooperation. We also thank Sigurd Hermansen and Kerry Grace Morrissey from Westat for study outcomes ascertainment and management and Leslie Carroll at Information Management Services for data support and analysis. We are deeply saddened by the loss of Dr Arthur Schatzkin, the principal investigator for the NIH-AARP Diet and Health Study, who passed away on 20 January 2011. The study was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. Megan A Murphy is supported in part by a training grant NIH 5 T32 CA09001-35. NR 27 TC 11 Z9 11 U1 1 U2 7 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 31 PY 2012 VL 106 IS 3 BP 596 EP 602 DI 10.1038/bjc.2011.572 PG 7 WC Oncology SC Oncology GA 892RC UT WOS:000300302300023 PM 22223086 ER PT J AU Ferrucci, LM Sinha, R Huang, WY Berndt, SI Katki, HA Schoen, RE Hayes, RB Cross, AJ AF Ferrucci, L. M. Sinha, R. Huang, W-Y Berndt, S. I. Katki, H. A. Schoen, R. E. Hayes, R. B. Cross, A. J. TI Meat consumption and the risk of incident distal colon and rectal adenoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE colorectal adenoma; diet; meat; haeme iron; meat mutagens; nitrate; nitrite ID COLORECTAL-CANCER RISK; EPOXIDE HYDROLASE POLYMORPHISMS; HETEROCYCLIC AMINE CONTENT; N-NITROSO COMPOUNDS; BODY IRON STORES; GRILLED RED MEAT; DIETARY IRON; WELL-DONE; HEME IRON; ALCOHOL-CONSUMPTION AB BACKGROUND: Most studies of meat and colorectal adenoma have investigated prevalent events from a single screening, thus limiting our understanding of the role of meat and meat-related exposures in early colorectal carcinogenesis. METHODS: Among participants in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who underwent baseline and follow-up sigmoidoscopy (n = 17 072), we identified 1008 individuals with incident distal colorectal adenoma. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between meat and meat-related components and incident distal colorectal adenoma using multivariate logistic regression. RESULTS: We observed suggestive positive associations for red meat, processed meat, haeme iron, and nitrate/nitrite with distal colorectal adenoma. Grilled meat (OR = 1.56, 95% CI = 1.04-2.36), well or very well-done meat (OR = 1.59, 95% CI = 1.05-2.43), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b] pyridine (PhIP) (OR = 1.75, 95% CI = 1.17-2.64), benzo[a] pyrene (OR = 1.53, 95% CI = 1.06-2.20), and total mutagenic activity (OR = 1.57, 95% CI = 1.03-2.40) were positively associated with rectal adenoma. Total iron (diet and supplements) (OR = 0.69, 95% CI = 0.56-0.86) and iron from supplements (OR = 0.65, 95% CI = 0.44-0.97) were inversely associated with any distal colorectal adenoma. CONCLUSION: Our findings indicate that several meat-related components may be most relevant to early neoplasia in the rectum. In contrast, total iron and iron from supplements were inversely associated with any distal colorectal adenoma. British Journal of Cancer (2012) 106, 608-616. doi: 10.1038/bjc.2011.549 www.bjcancer.com Published online 13 December 2011 (C) 2012 Cancer Research UK C1 [Ferrucci, L. M.; Sinha, R.; Huang, W-Y; Berndt, S. I.; Katki, H. A.; Cross, A. J.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Ferrucci, L. M.] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT USA. [Schoen, R. E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Hayes, R. B.] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. RP Cross, AJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM crossa@mail.nih.gov RI Katki, Hormuzd/B-4003-2015; Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Hayes, Richard/0000-0002-0918-661X FU National Institutes of Health, National Cancer Institute; National Cancer Institute [TU2 CA105666]; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, by grant TU2 CA105666 from the National Cancer Institute, and by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. We thank Drs Christine Berg, Paul Pinsky, and Philip Prorok, Division of Cancer Prevention, National Cancer Institute, the Screening Center investigators and staff of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, and Mr Tom Riley and staff, Information Management Services Inc. NR 63 TC 21 Z9 21 U1 0 U2 18 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 31 PY 2012 VL 106 IS 3 BP 608 EP 616 DI 10.1038/bjc.2011.549 PG 9 WC Oncology SC Oncology GA 892RC UT WOS:000300302300025 PM 22166801 ER PT J AU Xia, D Esser, L Tang, WK Zhang, MQ Yu, LD Yu, CA AF Xia, Di Esser, Lothar Tang, Wai-kwan Zhang, Mingquan Yu, Linda Yu, Chang-an TI Redox Coupled Conformational Changes in Cytochrome BC1 Complex: Implication to the Bifurcated Electron Transfer at the Quinol Oxidation Site 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 [Xia, Di] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. [Esser, Lothar; Tang, Wai-kwan] NCI, Bethesda, MD 20892 USA. [Zhang, Mingquan; Yu, Linda; Yu, Chang-an] Oklahoma State Univ, Stillwater, OK 74078 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 3A EP 3A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200015 ER PT J AU Hammer, JA Wagner, W Brenowitz, SD Wu, XFS Jung, G AF Hammer, John A. Wagner, Wolfgang Brenowitz, Stefan D. Wu, Xufeng S. Jung, Goeh TI Myosin V as a Point-to-Point Organelle Transporter 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 [Hammer, John A.] NIH, Cell Biol Lab, Bethesda, MD 20892 USA. [Wagner, Wolfgang; Brenowitz, Stefan D.; Wu, Xufeng S.; Jung, Goeh] NIH, Bethesda, MD 20892 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 5A EP 5A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200028 ER PT J AU Taraska, JW AF Taraska, Justin W. TI Imaging the Nanometer-Scale Architecture of Microvesicle Release and Recapture 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 [Taraska, Justin W.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 9A EP 9A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200048 ER PT J AU Koefinger, J Hummer, G AF Koefinger, Juergen Hummer, Gerhard TI Simple and Efficient Calculation of Scattering Intensities of Proteins in Solution from Atomistically Detailed Structures 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 [Koefinger, Juergen; Hummer, Gerhard] NIDDK, NIH, Bethesda, MD 20892 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 21A EP 21A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200109 ER PT J AU Kraft, ML Frisz, JF Lou, KY Klitzing, HA Hanafin, WP Weber, PK Zimmerberg, J AF Kraft, Mary L. Frisz, Jessica F. Lou, Kaiyan Klitzing, Haley A. Hanafin, William P. Weber, Peter K. Zimmerberg, Joshua TI Chemical Imaging of the Lipid and Cholesterol Distribution in the Plasma Membranes of Intact 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 [Kraft, Mary L.; Frisz, Jessica F.; Lou, Kaiyan; Klitzing, Haley A.; Hanafin, William P.] Univ Illinois, Urbana, IL 61801 USA. [Weber, Peter K.] Lawrence Livermore Natl Lab, Livermore, CA USA. [Zimmerberg, Joshua] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 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 26A EP 26A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200132 ER PT J AU King, KE Blaih-Isler, YE Jiang, ZP Gericke, A AF King, Katrice E. Blaih-Isler, Yasmin E. Jiang, Zhiping Gericke, Arne TI Cholesterol Dependent and Independent Domain Formation in Mixed Phosphatidylinositol/Phosphoinositide Model Membranes 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 [King, Katrice E.; Gericke, Arne] Worcester Polytech, Worcester, MA USA. [Blaih-Isler, Yasmin E.] Kent State Univ, Kent, OH 44242 USA. [Jiang, Zhiping] NIH, Bethesda, MD 20892 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 27A EP 27A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200135 ER PT J AU Itoh, SG Damjanovic, A Brooks, BR AF Itoh, Satoru G. Damjanovic, Ana Brooks, Bernard R. TI pH Replica-Exchange Method Based on Discrete Protonation States 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 [Itoh, Satoru G.] Inst Mol Sci, Okazaki, Aichi 444, Japan. [Itoh, Satoru G.] Grad Univ Adv Studies, Okazaki, Aichi, Japan. [Damjanovic, Ana] Johns Hopkins Univ, Baltimore, MD USA. [Damjanovic, Ana; Brooks, Bernard R.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 40A EP 40A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200200 ER PT J AU Maciejewski, M Tjandra, N Barlow, PN AF Maciejewski, Mateusz Tjandra, Nico Barlow, Paul N. TI Decoding the Components of Dynamics in Three-Domain Proteins 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 [Maciejewski, Mateusz; Tjandra, Nico] NIH, Bethesda, MD 20892 USA. [Maciejewski, Mateusz; Barlow, Paul N.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. 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 53A EP 53A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200264 ER PT J AU Wu, H McCauley, MJ Gorelick, RJ Rouzina, I Musier-Forsyth, K Williams, MC AF Wu, Hao McCauley, Micah J. Gorelick, Robert J. Rouzina, Ioulia Musier-Forsyth, Karin Williams, Mark C. TI Nucleic Acid Chaperone Activity of Wild Type and Mutant FIV Nucleocapsid Proteins 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 [Wu, Hao; McCauley, Micah J.; Williams, Mark C.] Northeastern Univ, Boston, MA 02115 USA. [Gorelick, Robert J.] SAIC Frederick Inc, AIDS & Canc Virus Program, NCI Frederick, Frederick, MD USA. [Rouzina, Ioulia] Univ Minnesota, Minneapolis, MN USA. [Musier-Forsyth, Karin] Ohio State Univ, Columbus, OH 43210 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 60A EP 60A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200304 ER PT J AU Perera, HD Keffer, J Bewley, C AF Perera, Hettiarachchige D. Keffer, Jessica Bewley, Carole TI The Mode of Action of FtsZ Inhibitors 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 [Perera, Hettiarachchige D.; Keffer, Jessica; Bewley, Carole] NIH, Rockville, MD 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 64A EP 64A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200325 ER PT J AU Jensen, MK Fei, JY Richard, AC Sternberg, SH Gonzalez, RL AF Jensen, Madeleine K. Fei, Jingyi Richard, Arianne C. Sternberg, Samuel H. Gonzalez, Ruben L., Jr. TI The Magnesium Dependence of Ribosome and tRNA Dynamics in Single Pre-Translocation Ribosomal Complexes 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 [Jensen, Madeleine K.; Richard, Arianne C.; Sternberg, Samuel H.; Gonzalez, Ruben L., Jr.] Columbia Univ, New York, NY USA. [Fei, Jingyi] Univ Illinois, Urbana, IL 61801 USA. [Richard, Arianne C.] NIH, Bathesda, MD USA. [Sternberg, Samuel H.] Univ Calif Berkeley, Berkeley, CA 94720 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 69A EP 69A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200347 ER PT J AU Dimitriadis, EK Qian, Z Adhya, S AF Dimitriadis, Emilios K. Qian, Zhong Adhya, Sankar TI GalR Mediated Interactions Across the E. Coli Chromosome 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 [Dimitriadis, Emilios K.] NIBIB, NIH, Bethesda, MD USA. [Qian, Zhong; Adhya, Sankar] NCI, NIH, Bethesda, MD 20892 USA. RI Qian, Zhong/N-2266-2014 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 73A EP 73A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200370 ER PT J AU DeRouchey, JE Rau, D AF DeRouchey, Jason E. Rau, Donald TI Role of Amino Acid Insertions on Intermolecular Forces Between Arginine Peptide Condensed DNA Helices: Implications for Protamine-DNA Packaging in Sperm 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 [DeRouchey, Jason E.] Univ Kentucky, Lexington, KY USA. [Rau, Donald] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 75A EP 75A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200380 ER PT J AU Walker, RL Pfefferkorn, CM He, Y Lee, JC AF Walker, Robert L. Pfefferkorn, Candace M. He, Yi Lee, Jennifer C. TI Tryptophan Probes at the Apolipoprotein C-III and Membrane Interface 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 [Walker, Robert L.; Pfefferkorn, Candace M.; He, Yi; Lee, Jennifer C.] NHLBI, NIH, Bethesda, MD 20892 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 77A EP 77A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200389 ER PT J AU Rostovtseva, TK Gurnev, PA Jacobs, D Weinrich, M Weinrich, M Bezrukov, SM AF Rostovtseva, Tatiana K. Gurnev, Philip A. Jacobs, Daniel Weinrich, Michael Weinrich, Michael Bezrukov, Sergey M. TI Interaction of Novel Anticancer Drug Erastin with Lipid Bilayers Probed by Gramicidin A 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 [Rostovtseva, Tatiana K.; Gurnev, Philip A.; Jacobs, Daniel; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD USA. [Weinrich, Michael; Weinrich, Michael] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Ctr Med Rehabil Res, Bethesda, MD 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 85A EP 85A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200430 ER PT J AU Roark, TC Palacio, LA Gurnev, PA Ray, BD Petrache, HI AF Roark, Torri C. Palacio, Luis A. Gurnev, Philip A. Ray, Bruce D. Petrache, Horia I. TI Interactions of Lithium Ions with Lipid Membranes 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 [Roark, Torri C.; Palacio, Luis A.; Ray, Bruce D.; Petrache, Horia I.] Indiana Univ Purdue Univ Indianapolis, Indianapolis, IN USA. [Gurnev, Philip A.] NIH, Bethesda, MD 20892 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 96A EP 96A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200484 ER PT J AU Song, KC Venable, RM Maliniak, A Im, W Gawrisch, K Pastor, RW AF Song, Kevin C. Venable, Richard M. Maliniak, Arnold Im, Wonpil Gawrisch, Klaus Pastor, Richard W. TI Molecular Dynamics Simulation, 31P-NMR Spectroscopy, and Microelectrophoretic Studies of Cardiolipin Bilayers 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 [Song, Kevin C.; Im, Wonpil] Univ Kansas, Lawrence, KS 66045 USA. [Venable, Richard M.] NIH, Betheda, MD USA. [Maliniak, Arnold] Stockholm Univ, S-10691 Stockholm, Sweden. [Gawrisch, Klaus; Pastor, Richard W.] NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 3 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 97A EP 97A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200490 ER PT J AU Monfredi, O Lakatta, EG Maltsev, VA AF Monfredi, Oliver Lakatta, Edward G. Maltsev, Victor A. TI Synchronization of Local Calcium Releases by Beta-Adrenergic Stimulation in Cardiac Pacemaker 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 [Monfredi, Oliver] Univ Manchester, Manchester, Lancs, England. [Monfredi, Oliver; Lakatta, Edward G.; Maltsev, Victor A.] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 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 103A EP 103A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200519 ER PT J AU Kumar, J Zhang, JJ Mayer, ML AF Kumar, Janesh Zhang, Jinjin Mayer, Mark L. TI Optimization of Constructs for Expression, Purification and Crystallization of Glutamate Receptor Ion Channels 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 [Kumar, Janesh; Zhang, Jinjin; Mayer, Mark L.] NICHD, NIH, Bethesda, MD 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 116A EP 116A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200584 ER PT J AU Lopez-Rodriguez, AM Holmgren, M AF Lopez-Rodriguez, Angelica M. Holmgren, Miguel TI Rescuing Proper Trafficking of Cysteine Mutant Proteins 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 [Lopez-Rodriguez, Angelica M.; Holmgren, Miguel] NIH, Bethesda, MD 20892 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 130A EP 130A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200654 ER PT J AU Raghunathan, M Zubovski, Y Venable, RM Pastor, RW Nagle, JF Tristram-Nagle, S AF Raghunathan, Mohit Zubovski, Yuriy Venable, Richard M. Pastor, Richard W. Nagle, John F. Tristram-Nagle, Stephanie TI Structure and Elasticity of Genistein and Daidzein in Lipid Membranes using X-Ray Scattering and MD Simulations 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 [Raghunathan, Mohit; Zubovski, Yuriy; Nagle, John F.; Tristram-Nagle, Stephanie] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Venable, Richard M.; Pastor, Richard W.] NHLBI, Bethesda, MD 20892 USA. RI Nagle, John/B-1917-2015; Tristram-Nagle, Prof. Stephanie/N-7811-2014 OI Nagle, John/0000-0002-9844-5934; Tristram-Nagle, Prof. Stephanie/0000-0003-2271-7056 NR 1 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 136A EP 136A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561200683 ER PT J AU Gurnev, PA Martin, MQ Aguilella, VM Rostovtseva, TK Bezrukov, SM AF Gurnev, Philip A. Martin, Maria Queralt Aguilella, Vicente M. Rostovtseva, Tatiana K. Bezrukov, Sergey M. TI Tubulin-Blocked State of VDAC Probed by Polymer Partitioning and Bilayer Surface Charge 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 [Gurnev, Philip A.; Rostovtseva, Tatiana K.; Bezrukov, Sergey M.] NICHHD, Bethesda, MD 20892 USA. [Martin, Maria Queralt; Aguilella, Vicente M.] Univ Jaume 1, Dept Phys, Lab Mol Biophys, Castellon De La Plama 12071, Castellon, Spain. RI Aguilella, Vicente/B-7592-2008 OI Aguilella, Vicente/0000-0002-2420-2649 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 161A EP 161A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201103 ER PT J AU Hermida, OT Bezrukov, SM Rostovtseva, TK AF Hermida, Oscar Teijido Bezrukov, Sergey M. Rostovtseva, Tatiana K. TI A Putative Role of Voltage-Dependent Anion Channel in Ischemia 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 [Hermida, Oscar Teijido; Bezrukov, Sergey M.; Rostovtseva, Tatiana K.] NIH, Bethesda, MD 20892 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 161A EP 161A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201101 ER PT J AU Rostovtseva, TK Sheldon, KL Gurnev, PA Bezrukov, SM AF Rostovtseva, Tatiana K. Sheldon, Kely L. Gurnev, Philip A. Bezrukov, Sergey M. TI VDAC Regulation by Tubulin and its Physiological Implications 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 [Rostovtseva, Tatiana K.; Sheldon, Kely L.; Gurnev, Philip A.; Bezrukov, Sergey M.] NICHD, NIH, Bethesda, MD 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 161A EP 161A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201102 ER PT J AU Wu, XW Hodoscek, M Brooks, BR AF Wu, Xiongwu Hodoscek, Milan Brooks, Bernard R. TI Replica Exchange of Self-Guided Langevin Dynamics Simulation 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 [Wu, Xiongwu; Brooks, Bernard R.] NIH, Bethesda, MD 20892 USA. [Hodoscek, Milan] Natl Inst Chem, Hajdrihova, Slovenia. NR 0 TC 0 Z9 0 U1 0 U2 4 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 171A EP 171A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201153 ER PT J AU Zhao, HY Brown, PH Magone, MT Schuck, P AF Zhao, Huaying Brown, Patrick H. Magone, M. Teresa Schuck, Peter TI The Molecular Refractive Function of Lens Gamma Crystallins 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 [Zhao, Huaying; Brown, Patrick H.; Magone, M. Teresa; Schuck, Peter] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 185A EP 185A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201230 ER PT J AU Lee, JY Tokumasu, F Sackett, D Nossal, R Hwang, J AF Lee, Ji Youn Tokumasu, Fuyuki Sackett, Dan Nossal, Ralph Hwang, Jeeseong TI Label-Free Hyperspectral Imaging of Intracellular Hemoglobin in Human Erythrocytes 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 [Lee, Ji Youn; Hwang, Jeeseong] NIST, Gaithersburg, MD 20899 USA. [Tokumasu, Fuyuki; Sackett, Dan; Nossal, Ralph] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 195A EP 195A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201280 ER PT J AU Chung, HS Gopich, IV McHale, K Louis, JM Eaton, WA AF Chung, Hoi Sung Gopich, Irina V. McHale, Kevin Louis, John M. Eaton, William A. TI Measurement of Average Transition-Path Time for Protein Folding in Single Molecule FRET Experiments 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 [Chung, Hoi Sung; Gopich, Irina V.; McHale, Kevin; Louis, John M.; Eaton, William A.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 5 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 217A EP 218A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201400 ER PT J AU Johnson, ME Hummer, G AF Johnson, Margaret E. Hummer, Gerhard TI Refining Protein Interaction Networks with Protein Structure and Kinetic Modeling 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 [Johnson, Margaret E.; Hummer, Gerhard] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 226A EP 226A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201442 ER PT J AU Stasevich, TJ Hayashi-Takanaka, Y Nozaki, N McNally, JG Kimura, H AF Stasevich, Timothy J. Hayashi-Takanaka, Yoko Nozaki, Naohito McNally, James G. Kimura, Hiroshi TI Visualizing the Transcription Cycle of Endogenous RNA Polymerase II in Single Living 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 [Stasevich, Timothy J.; Hayashi-Takanaka, Yoko; Kimura, Hiroshi] Osaka Univ, Osaka, Japan. [Nozaki, Naohito] MAB Inst Inc, Sapporo, Hokkaido, Japan. [McNally, James G.] NCI, Bethesda, MD 20892 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 228A EP 228A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201452 ER PT J AU Adhya, S AF Adhya, Sankar TI Bacterial Chromosome Structure and Function 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 [Adhya, Sankar] NIH, Bethesda, MD 20892 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 233A EP 233A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201475 ER PT J AU Gopich, IV Szabo, A AF Gopich, Irina V. Szabo, Attila TI Single-Molecule FRET: Theory and Analysis of Photon Sequences 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 [Gopich, Irina V.; Szabo, Attila] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 235A EP 235A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201487 ER PT J AU Nguyen, TA Sarkar, P Veetil, JV Koushik, SV Thaler, C Vogel, SS AF Nguyen, Tuan A. Sarkar, Pabak Veetil, Jithesh V. Koushik, Srinagesh V. Thaler, Christopher Vogel, Steven S. TI Polarized Fluorescence Correlation Spectroscopy (pFCS): A Single-Molecule Method for Simultaneously Measuring Homo-FRET, Brightness, and the Diffusion of Protein Complexes in Living 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 [Nguyen, Tuan A.; Sarkar, Pabak; Veetil, Jithesh V.; Koushik, Srinagesh V.; Thaler, Christopher; Vogel, Steven S.] NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 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 235A EP 235A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201485 ER PT J AU Renner, LD Eswaramoorthy, P Ramamurthi, KS Weibel, DB AF Renner, Lars D. Eswaramoorthy, Prahathees Ramamurthi, Kumaran S. Weibel, Douglas B. TI Curvature as a Mechanism for Biomolecule Localization in Bacterial 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 [Renner, Lars D.; Weibel, Douglas B.] Univ Wisconsin, Madison, WI USA. [Eswaramoorthy, Prahathees; Ramamurthi, Kumaran S.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 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 237A EP 237A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201498 ER PT J AU Kimura, T Macke, L Gawrisch, K Yeliseev, A AF Kimura, Tomohiro Macke, Laura Gawrisch, Klaus Yeliseev, Alexei TI Effect of Anionic Lipids on Structure and Function of Cannabinoid CB2 Receptor in Micelles and in Reconstituted Liposomes 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 [Kimura, Tomohiro; Macke, Laura; Gawrisch, Klaus; Yeliseev, Alexei] NIAAA, NIH, Bethesda, MD 90034 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 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 240A EP 240A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201513 ER PT J AU Brown, PH AF Brown, Patrick H. TI Density Contrast Sedimentation Velocity for the Determination of Protein Partial-Specific Volumes 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 [Brown, Patrick H.] NIBIB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 3 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 258A EP 258A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561201609 ER PT J AU Ishibashi, T Bintu, L Dangkulwanich, M Gloria, W Lubkowska, L Kashlev, M Bustamante, C AF Ishibashi, Toyotaka Bintu, Lacramioara Dangkulwanich, Manchuta Gloria, Wu Lubkowska, Lucyna Kashlev, Mikhail Bustamante, Carlos TI Dissecting the Nucleosomal Barrier to Transcription 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 [Ishibashi, Toyotaka; Bintu, Lacramioara; Dangkulwanich, Manchuta; Gloria, Wu; Bustamante, Carlos] Univ Calif Berkeley, Berkeley, CA USA. [Lubkowska, Lucyna; Kashlev, Mikhail] NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. [Bustamante, Carlos] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. OI Ishibashi, Toyotaka/0000-0001-8015-2319 NR 0 TC 0 Z9 0 U1 0 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 284A EP 284A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202027 ER PT J AU Nanda, H Weinrich, M Majkrzak, CF Maranville, BB Worcester, DL Bezrukov, SM AF Nanda, Hirsh Weinrich, Michael Majkrzak, Charles F. Maranville, Brian B. Worcester, David L. Bezrukov, Sergey M. TI Anesthetic Concentrations of Halothane Change the Domain Structure of Mixed Lipid Membranes 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 [Nanda, Hirsh; Majkrzak, Charles F.; Maranville, Brian B.; Worcester, David L.; Bezrukov, Sergey M.] NIST, Gaithersburg, MD 20899 USA. [Weinrich, Michael] NIH, Bethesda, MD 20892 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 288A EP 288A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202049 ER PT J AU Sodt, AJ Pastor, RW AF Sodt, Alex J. Pastor, Richard W. TI Lipid Mechanical Properties from Computer Simulation 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 [Sodt, Alex J.; Pastor, Richard W.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 291A EP 291A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202065 ER PT J AU Galimzyanov, TR Molotkovsky, RJ Jimmerberg, J Akimov, SA Cohen, FS AF Galimzyanov, Timur R. Molotkovsky, Rodion J. Jimmerberg, Joshua Akimov, Sergey A. Cohen, Fredric S. TI Elastic Deformations at a Boundary Stabilizes Opposion of Monolayer Rafts in the Structure of a Bilayer Raft 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 [Galimzyanov, Timur R.] Natl Univ Sci & Technol MISiS, Moscow, Russia. [Molotkovsky, Rodion J.; Akimov, Sergey A.] Russian Acad Sci, AN Frumkin Inst Phys Chem & Electrochem, Moscow, Russia. [Jimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD USA. [Cohen, Fredric S.] Rush Univ, Med Ctr, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA. RI Akimov, Sergey/L-2001-2013; Galimzyanov, Timur/I-6297-2015; Akimov, Sergey/I-6432-2015 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 295A EP 295A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202088 ER PT J AU Lee, KI Kim, T Pastor, RW Andersen, OS Im, W AF Lee, Kyu Il Kim, Taehoon Pastor, Richard W. Andersen, Olaf S. Im, Wonpil TI Assessment of Membrane Deformation Continuum Elastic Models Based on Molecular Simulations of Gramicidin A 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 [Lee, Kyu Il; Kim, Taehoon; Im, Wonpil] Univ Kansas, Lawrence, KS 66045 USA. [Pastor, Richard W.] NIH, Bethesda, MD 20892 USA. [Andersen, Olaf S.] Weill Cornell Med Coll, New York, NY 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 296A EP 296A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202090 ER PT J AU Lizunov, VA Stenkula, K Cushman, S Zimmerberg, J AF Lizunov, Vladimir A. Stenkula, Karin Cushman, Samuel Zimmerberg, Joshua TI Fence Model for Dynamic Exchange and Retention of GLUT4 in Plasma Membrane Domains 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 [Lizunov, Vladimir A.; Cushman, Samuel; Zimmerberg, Joshua] NIH, Bethesda, MD 20892 USA. [Stenkula, Karin] Lund Univ, Lund, Sweden. 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 320A EP 321A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202206 ER PT J AU Banerjee, A Nossal, R AF Banerjee, Anand Nossal, Ralph TI Stochastic Nature of Clathrin-Coated Pit Assembly 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 [Banerjee, Anand; Nossal, Ralph] NIH, Bethesda, MD 20892 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 321A EP 321A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202209 ER PT J AU Hinshaw, JE Chappie, JS Mears, JA Fang, SM Leonard, M Schmid, SL Milligan, RA Dyda, F AF Hinshaw, Jenny E. Chappie, Joshua S. Mears, Jason A. Fang, Shunming Leonard, Marilyn Schmid, Sandra L. Milligan, Ronald A. Dyda, Fred TI Structural Analysis of Dynamin Reveals Power Stroke 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 [Hinshaw, Jenny E.; Chappie, Joshua S.; Fang, Shunming; Dyda, Fred] NIDDK, NIH, Bethesda, MD USA. [Mears, Jason A.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Leonard, Marilyn; Schmid, Sandra L.; Milligan, Ronald A.] Scripps Res Inst, La Jolla, CA 92037 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 321A EP 321A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202211 ER PT J AU Shnyrova, A Bashkirov, PV Hortelano, ER Zimmerberg, J Frolov, VA AF Shnyrova, Anna Bashkirov, Pavel V. Rodriguez Hortelano, Eva Zimmerberg, Joshua Frolov, Vadim A. TI Spatio-Temporal Organization of a Minimal Dynamin Machinery Producing Membrane Fission 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 [Shnyrova, Anna; Rodriguez Hortelano, Eva; Frolov, Vadim A.] Univ Basque Country, Dept Bioquim, EHU, Unidad Biofis,Ctr Mixto,CSIC,UPV, E-48080 Bilbao, Spain. [Bashkirov, Pavel V.] AN Frumkin Inst Phys Chem & Elecrochem, Moscow, Russia. [Zimmerberg, Joshua] Eunice Kennedy Schriver Natl Inst Child Hlth & Hu, Program Phys Biol, NIH, Bethesda, MD USA. [Frolov, Vadim A.] Basque Fdn Sci, IKERBASQUE, Bilbao, Spain. NR 0 TC 0 Z9 0 U1 1 U2 3 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 322A EP 322A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202214 ER PT J AU Bosmans, F Swartz, KJ AF Bosmans, Frank Swartz, Kenton J. TI Sodium Channel Voltage Sensor Movements Are Influenced by the Auxiliary beta 1 Subunit 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 [Bosmans, Frank; Swartz, Kenton J.] NIH, Bethesda, MD 20892 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 326A EP 326A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202235 ER PT J AU Berger, AJ Brown, P Zhao, HY Schuck, P Mayer, M AF Berger, Anthony J. Brown, Patrick Zhao, Huaying Schuck, Peter Mayer, Mark TI Analysis of Oligomer Assembly for the GluA2 Amino Terminal Domain 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 ID CRYSTAL-STRUCTURE C1 [Berger, Anthony J.; Brown, Patrick; Zhao, Huaying; Schuck, Peter; Mayer, Mark] NIH, Bethesda, MD 20892 USA. NR 3 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 335A EP 336A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202282 ER PT J AU Li, MF Silberberg, SD Swartz, KJ AF Li, Mufeng Silberberg, Shai D. Swartz, Kenton J. TI Subtype Specific Activation of P2X Receptors by Free and Magnesium-Bound ATP 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 [Li, Mufeng; Silberberg, Shai D.; Swartz, Kenton J.] NINDS, NIH, Bethesda, MD 20892 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 336A EP 337A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202287 ER PT J AU Khadra, A AF Khadra, Anmar TI Understanding the Kinetics of ATP-Activated P2X2A and P2X2B Receptor Channels using a Markov State Model 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 [Khadra, Anmar] NIH, Bethesda, MD USA. [Khadra, Anmar] McGill Univ, Montreal, PQ, Canada. 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 337A EP 337A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202289 ER PT J AU Ladt, KC Bae, C Yu, J Kim, JI Swartz, K AF Ladt, Kelsey C. Bae, Chanhyung Yu, JeongHeon Kim, Jae Il Swartz, Kenton TI Activation of TRPV1 by a Recombinant Double-Knot Toxin from a Chinese Bird Spider 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 [Ladt, Kelsey C.; Swartz, Kenton] NIH, Bethesda, MD 20892 USA. [Bae, Chanhyung; Yu, JeongHeon; Kim, Jae Il] Gwangju Inst Sci & Technol, Kwangju, South Korea. 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 342A EP 342A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202312 ER PT J AU Smith, DB Liu, J AF Smith, Daniel B. Liu, Jian TI The Geometry of Branching Actin Networks from Capping Branching and Filament Growth 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 [Smith, Daniel B.] Univ Pittsburgh, Pittsburgh, PA USA. [Liu, Jian] NHBLI, NIH, Bethesda, MD 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 348A EP 348A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202348 ER PT J AU Toepfer, C Caorsi, V Mansfield, C West, TG Kampourakis, T Leung, J Sellers, JR Ferenczi, MA AF Toepfer, Christopher Caorsi, Valentina Mansfield, Catherine West, Timothy G. Kampourakis, Thomas Leung, Judy Sellers, James R. Ferenczi, Michael A. TI A Method to Exchange Recombinant Differentially Phosphorylated Rhodamine-Labeled Cardiac RLC into Permeabilized Cardiac Trabeculae 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 [Toepfer, Christopher; Caorsi, Valentina; Mansfield, Catherine; Leung, Judy; Ferenczi, Michael A.] Univ London Imperial Coll Sci Technol & Med, London, England. [West, Timothy G.] Univ London Royal Vet Coll, London, England. [Kampourakis, Thomas] Kings Coll London, London WC2R 2LS, England. [Sellers, James R.] NIH, Bethesda, MD 20892 USA. RI Ferenczi, Michael/F-9510-2015 OI Ferenczi, Michael/0000-0002-0349-331X 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 359A EP 359A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202398 ER PT J AU Vecchiarelli, A Mizuuchi, K AF Vecchiarelli, Anthony Mizuuchi, Kiyoshi TI Visualizing Bacterial DNA Segregation in a Cell Free System 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 [Vecchiarelli, Anthony; Mizuuchi, Kiyoshi] NIH, Bethesda, MD 20892 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 380A EP 381A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202514 ER PT J AU Hwang, LC Han, YW Vecchiarelli, AG Harada, Y Funnell, BE Mizuuchi, K AF Hwang, Ling Chin Han, Yong-Woon Vecchiarelli, Anthony G. Harada, Yoshie Funnell, Barbara E. Mizuuchi, Kiyoshi TI Dynamic Self-Organization of Bacterial DNA Segregation Machinery in a Cell-Free Reaction 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 [Hwang, Ling Chin; Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi] NIH, Bethesda, MD 20892 USA. [Han, Yong-Woon; Harada, Yoshie] Inst Integrated Cell Mat Sci, Kyoto, Japan. [Funnell, Barbara E.] Dept Mol Genet, Toronto, ON, Canada. RI Hwang, Ling Chin/G-4078-2014 NR 0 TC 0 Z9 0 U1 0 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 381A EP 381A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202515 ER PT J AU Sharma, G Stupina, V Pallesen, J Shapiro, B Simon, A Dinman, J Frank, J AF Sharma, Gyanesh Stupina, Vera Pallesen, Jesper Shapiro, Bruce Simon, Anne Dinman, Jonathan Frank, Joachim TI Cryo-Electron Microscopy (Cryo-EM) Structure of a Cap-Independent Translational Enhancer of the Turnip Crinkle Virus (TCV) Bound to the Eukaryotic Ribosome 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 [Sharma, Gyanesh; Pallesen, Jesper; Frank, Joachim] Columbia Univ, New York, NY USA. [Stupina, Vera; Simon, Anne; Dinman, Jonathan] Univ Maryland, College Pk, MD 20742 USA. [Shapiro, Bruce] NCI, Frederick, MD 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 393A EP 393A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202575 ER PT J AU Sousa, AA Winters, CA Cox, D Chen, XB Reese, TS Leapman, RD AF Sousa, Alioscka A. Winters, Christine A. Cox, Daniel Chen, Xiaobing Reese, Thomas S. Leapman, Richard D. TI Three-Dimensional Ultrastructure of Micrometer Thick Cellular Subvolumes by STEM Tomography 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 [Sousa, Alioscka A.; Cox, Daniel; Leapman, Richard D.] NIBIB, NIH, Bethesda, MD USA. [Winters, Christine A.; Chen, Xiaobing; Reese, Thomas S.] NINDS, NIH, Bethesda, MD 20892 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 393A EP 393A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202574 ER PT J AU Hayakawa, EH Tokumasu, F Usukura, J Tsuboi, T Matsuoka, H Wellems, TE AF Hayakawa, Eri H. Tokumasu, Fuyuki Usukura, Jiro Tsuboi, Takafumi Matsuoka, Hiroyuki Wellems, Thomas E. TI Three Dimensional Imaging of Maurer's Clefts in "Unroofed" Plasmodium Falciparum-Infected Erythrocytes by Transmission Electron Microscopy 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 [Hayakawa, Eri H.; Matsuoka, Hiroyuki] Jichi Med Univ, Dept Infect & Immun, Lab Med Zool & Parasitol, Shimotsuke, Japan. [Tokumasu, Fuyuki; Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Usukura, Jiro] Nagoya Univ, Div Integrated Project, EcoTopia Sci Inst, Nagoya, Aichi 4648601, Japan. [Tsuboi, Takafumi] Ehime Univ, Cell Free Sci & Technol Res Ctr, Malaria Res Unit, Matsuyama, Ehime, Japan. 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 395A EP 395A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202585 ER PT J AU Heymann, J Fontainhas, A Fang, SM Hinshaw, JE AF Heymann, Jurgen Fontainhas, Aurora Fang, Shunming Hinshaw, Jenny E. TI Molecular Architecture of OPA1, the Dynamin-Related GTPase Involved in Mitochondrial Fusion 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 [Heymann, Jurgen; Fontainhas, Aurora; Fang, Shunming; Hinshaw, Jenny E.] NIDDK, NIH, LCBB, Bethesda, MD USA. NR 1 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 395A EP 395A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202587 ER PT J AU Drobizhev, M Hughes, TE Rebane, A Davis, B Topol, I Scott, N Callis, PR AF Drobizhev, Mikhail Hughes, Thomas E. Rebane, Aleksander Davis, Bret Topol, Igor Scott, Nathan Callis, Patrik R. TI Unified Description of Optical Properties and Photostability of Fluorescent Proteins by Means of the Chromophore-Protein Electrostatic Interactions 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 [Drobizhev, Mikhail; Hughes, Thomas E.; Rebane, Aleksander; Davis, Bret; Scott, Nathan; Callis, Patrik R.] Montana State Univ, Bozeman, MT 59717 USA. [Topol, Igor] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 403A EP 404A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202630 ER PT J AU Yu, XZ Taraska, J AF Yu, Xiaozhen Taraska, Justin TI High-Throughput Protein Structural Mapping using Transition Metal FRET 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 [Yu, Xiaozhen; Taraska, Justin] NIH, Bethesda, MD 20892 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 403A EP 403A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202625 ER PT J AU Teague, WE Soubias, O Fuller, NL Rand, RP Gawrisch, K AF Teague, Walter E. Soubias, Olivier Fuller, Nola L. Rand, R. Peter Gawrisch, Klaus TI Curvature Elastic Properties of Phosphatidylethanolamines with Mono- and Polyunsaturated Hydrocarbon Chains - An NMR and X-Ray Diffraction Study 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 [Teague, Walter E.; Soubias, Olivier; Gawrisch, Klaus] NIAAA, NIH, Bethesda, MD 90034 USA. [Fuller, Nola L.; Rand, R. Peter] Brock Univ, St Catharines, ON L2S 3A1, Canada. NR 0 TC 0 Z9 0 U1 1 U2 3 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 413A EP 413A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561202676 ER PT J AU Renz, M Daniels, B Vamosi, G Arias, I Lippincott-Schwartz, J AF Renz, Malte Daniels, Brian Vamosi, Gyorgy Arias, Irwin Lippincott-Schwartz, Jennifer TI Plasticity of the Asialoglycoprotein Receptor Deciphered by Ensemble FRET and Single-Molecule Counting PALM 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 [Renz, Malte; Daniels, Brian; Arias, Irwin; Lippincott-Schwartz, Jennifer] NIH, Bethesda, MD 20892 USA. [Vamosi, Gyorgy] Univ Debrecen, H-4012 Debrecen, Hungary. 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 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 31 PY 2012 VL 102 IS 3 SU 1 BP 430A EP 430A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203052 ER PT J AU Jiang, ZP McGlinchey, RP Pfefferkorn, CM Lee, JC AF Jiang, Zhiping McGlinchey, Ryan P. Pfefferkorn, Candace M. Lee, Jennifer C. TI Effects of Lipids on the Conformation and Aggregation of the Repeat Domain of a Functional Amyloid, Pmel17 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 [Jiang, Zhiping; McGlinchey, Ryan P.; Pfefferkorn, Candace M.; Lee, Jennifer C.] NHLBI, NIH, Bethesda, MD 20892 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 434A EP 434A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203072 ER PT J AU Soubias, O Teague, WE Hines, KG Gawrisch, K AF Soubias, Olivier Teague, Walter E. Hines, Kirk G. Gawrisch, Klaus TI Cholesterol Enhances or Reduces Metarhodopsin II Formation Depending on Bilayer Thickness 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 [Soubias, Olivier; Teague, Walter E.; Hines, Kirk G.; Gawrisch, Klaus] NIH, Rockville, MD 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 434A EP 435A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203075 ER PT J AU Sheldon, KL Maldonado, EN Lemasters, JJ Bezrukov, SM Rostovtseva, TK AF Sheldon, Kely L. Maldonado, Eduardo N. Lemasters, John J. Bezrukov, Sergey M. Rostovtseva, Tatiana K. TI VDAC Phosphorylation in Control of Mitochondrial Respiration 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 [Sheldon, Kely L.; Bezrukov, Sergey M.; Rostovtseva, Tatiana K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA. [Sheldon, Kely L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Maldonado, Eduardo N.; Lemasters, John J.] Med Univ S Carolina, Charleston, SC 29425 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 436A EP 437A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203084 ER PT J AU Dejean, LM Renault, TT Teijido, O Velours, G Ganesan, YT Camougrand, N Antonsson, B Manon, S AF Dejean, Laurent M. Renault, Thibaud T. Teijido, Oscar Velours, Gisele Ganesan, Yogesh Tengarai Camougrand, Nadine Antonsson, Bruno Manon, Stephen TI Bcl-xL Increases Bax Mitochondrial Localization and Activation in Non-Apoptotic 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 [Dejean, Laurent M.] Calif State Univ Fresno, Fresno, CA 93740 USA. [Renault, Thibaud T.; Velours, Gisele; Camougrand, Nadine; Manon, Stephen] CNRS, Inst Biochim & Genet Cellulaires, Bordeaux, France. [Teijido, Oscar] NICHD, NIH, Bethesda, MD USA. [Ganesan, Yogesh Tengarai] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Antonsson, Bruno] Merck Serrono SA, Geneva Res Ctr, Geneva, Switzerland. RI Manon, Stephen/C-7088-2017 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 437A EP 437A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203088 ER PT J AU Jang, H Capone, R Kotler, SA Arce, FT Connelly, L Ramachandran, S Kagan, BL Lal, R Nussinov, R AF Jang, Hyunbum Capone, Ricardo Kotler, Samuel A. Arce, Fernando Teran Connelly, Laura Ramachandran, Srinivasan Kagan, Bruce L. Lal, Ratnesh Nussinov, Ruth TI Modeling Alzheimer's Ion Channel Structures in Lipid Bilayers Formed by D- and L-Enantiomers of Beta-Amyloid (1-42) Peptide 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 [Jang, Hyunbum; Nussinov, Ruth] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Capone, Ricardo; Kotler, Samuel A.; Arce, Fernando Teran; Connelly, Laura; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, La Jolla, CA 92093 USA. [Kagan, Bruce L.] Univ Calif Los Angeles, Los Angeles, CA USA. RI Ramachandran, Srinivasan/G-5300-2010 OI Ramachandran, Srinivasan/0000-0002-4912-0279 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 440A EP 440A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203101 ER PT J AU Musselman, CA Ramirez, J Sims, JK Mansfield, RE Oliver, SS Denu, JM Mackay, JP Wade, PA Hagman, J Kutateladze, TG AF Musselman, Catherine A. Ramirez, Julita Sims, Jennifer K. Mansfield, Robyn E. Oliver, Samuel S. Denu, John M. Mackay, Joel P. Wade, Paul A. Hagman, James Kutateladze, Tatiana G. TI Bivalent Recognition of a Single Nucleosome by the Tandem PHD Fingers of CHD4 is Required for CHD4-Mediated Repression 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 [Musselman, Catherine A.; Kutateladze, Tatiana G.] Univ Colorado Denver, Aurora, CO USA. [Ramirez, Julita; Hagman, James] Natl Jewish Hlth, Denver, CO USA. [Sims, Jennifer K.; Wade, Paul A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Mansfield, Robyn E.; Mackay, Joel P.] Univ Sydney, Sydney, NSW 2006, Australia. [Oliver, Samuel S.; Denu, John M.] Univ Wisconsin, Madison, WI 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 480A EP 480A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203312 ER PT J AU Zhurkin, V Nikitina, T Wang, DF Cui, F Gomberg, M Grigoryev, S AF Zhurkin, Victor Nikitina, Tatiana Wang, Difei Cui, Feng Gomberg, Michael Grigoryev, Sergei TI Sequence-Specific Asymmetric Binding of Linker Histone to Nucleosome 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 [Zhurkin, Victor; Nikitina, Tatiana; Wang, Difei; Cui, Feng] NIH, Bethesda, MD 20892 USA. [Gomberg, Michael; Grigoryev, Sergei] Penn State Univ, Coll Med, Hershey, PA USA. RI Wang, Difei/E-7066-2010 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 481A EP 481A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203319 ER PT J AU Ma, BY Xu, Y Nussinov, R AF Ma, Buyong Xu, Yu Nussinov, Ruth TI Structural and Functional Consequences of Phosphate-Arsenate Substitutions in Selected Nucleotides: DNA, RNA, and ATP 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 [Ma, Buyong; Nussinov, Ruth] NCI, SAIC Frederick, NIH, Frederick, MD 21701 USA. [Xu, Yu] Minzu Univ China, Beijing, Peoples R China. 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 483A EP 483A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203329 ER PT J AU Sidorova, NY Hung, S Rau, DC AF Sidorova, Nina Y. Hung, Stevephen Rau, Donald C. TI Stabilizing Labile DNA-Protein Complexes in Polyacrylamide Gels 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 [Sidorova, Nina Y.; Hung, Stevephen; Rau, Donald C.] NIH, Bethesda, MD 20892 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 484A EP 484A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203336 ER PT J AU Seol, Y Zhang, HL Dalla Rosa, I Pommier, Y Neuman, KC AF Seol, Yeonee Zhang, Hongliang Dalla Rosa, Ilaria Pommier, Yves Neuman, Keir C. TI Distinct Uncoiling Mechanisms of Human Nuclear and Mitochondrial Type IB Topoisomerases 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 [Seol, Yeonee; Neuman, Keir C.] NHLBI, NIH, Bethesda, MD 20892 USA. [Zhang, Hongliang; Dalla Rosa, Ilaria; Pommier, Yves] NCI, NIH, Bethesda, MD 20892 USA. RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 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 485A EP 485A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203339 ER PT J AU Seol, Y Hardin, AH Charvin, G Neuman, KC AF Seol, Yeonee Hardin, Ashley H. Charvin, Gilles Neuman, Keir C. TI Non-Equilibrium Topology Simplification by Type II Topoisomerases: A Test of Kinetic Proofreading 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 ID DNA C1 [Seol, Yeonee; Hardin, Ashley H.; Neuman, Keir C.] NIH, Bethesda, MD 20892 USA. [Charvin, Gilles] Inst Biol Mol & Cellulaire, Illkirch Graffenstaden, France. RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 NR 2 TC 0 Z9 0 U1 0 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 486A EP 487A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203348 ER PT J AU Franquelim, HG Veiga, AS Santos, NC Castanho, MA AF Franquelim, Henri G. Veiga, A. Salome Santos, Nuno C. Castanho, Miguel A. TI Decoding Distinct Membrane Interactions of HIV-1 Inhibitors Enfuvirtide and T-1249 using Atomic Force Microscopy Combined with Fluorescence Methodologies 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 [Franquelim, Henri G.; Veiga, A. Salome; Santos, Nuno C.; Castanho, Miguel A.] Inst Mol Med, Lisbon, Portugal. [Veiga, A. Salome] NCI, Frederick, MD 21701 USA. RI Santos, Nuno/N-7248-2013 OI Santos, Nuno/0000-0002-0580-0475 NR 0 TC 0 Z9 0 U1 0 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 490A EP 490A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203365 ER PT J AU Zhang, LQ Sodt, A Venable, R Pastor, RW Buck, M AF Zhang, Liqun Sodt, Alexander Venable, Rick Pastor, Richard W. Buck, Matthias TI Molecular Dynamics Prediction and Refinement of Transmembrane Helix Dimers 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 [Zhang, Liqun; Buck, Matthias] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Sodt, Alexander; Venable, Rick] NHLBI, Bethesda, MD 20892 USA. [Pastor, Richard W.] NHBLI, Bethesda, MD 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 497A EP 498A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203402 ER PT J AU Chen, Y Lippincott-Schwartz, J AF Chen, Yu Lippincott-Schwartz, Jennifer TI Tirfing Insulin-Stimulated GLUT4 Translocation with a Quench-Based Mehtod 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 [Chen, Yu; Lippincott-Schwartz, Jennifer] NIH, Bethesda, MD 20892 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 500A EP 500A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203418 ER PT J AU Molotkovsky, R Zimmerberg, J Cohen, FS Akimov, S AF Molotkovsky, Rodion Zimmerberg, Joshua Cohen, Fredric S. Akimov, Sergey TI A Quantitative Model for Formation of Protein-Mediated Protrusions, Based on Continuum Elasticity Theory 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 [Molotkovsky, Rodion; Akimov, Sergey] RAS, IPCE, Moscow 117901, Russia. [Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Cohen, Fredric S.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RI Akimov, Sergey/L-2001-2013 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 500A EP 500A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203417 ER PT J AU Vinogradova, TM Lakatta, EG AF Vinogradova, Tatiana M. Lakatta, Edward G. TI Basal PKC Activity Regulates Spontaneous Firing of Cardiac Pacemaker 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 [Vinogradova, Tatiana M.; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 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 511A EP 511A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203473 ER PT J AU Yaniv, Y Maltsev, VA Lakatta, EG AF Yaniv, Yael Maltsev, Victor A. Lakatta, Edward G. TI How Ca2+-Activated, cAMP/PKA-Dependent Phosphorylation Signaling Mediates Pacemaker Cell Activity: Experimental and In Silico Biochemical and Biophysics Perspectives 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 [Yaniv, Yael; Maltsev, Victor A.; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 USA. RI Yaniv, Yael/B-3311-2015 OI Yaniv, Yael/0000-0002-5183-6284 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 511A EP 511A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203474 ER PT J AU Kalia, J Swartz, KJ AF Kalia, Jeet Swartz, Kenton J. TI Mechanism of Inhibition of Voltage-Gated Potassium Channels by Guanidine Compounds 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 [Kalia, Jeet; Swartz, Kenton J.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 533A EP 533A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203584 ER PT J AU Ganapathi, SB Wei, SG Lamb, FS Shears, SB AF Ganapathi, Sindura B. Wei, Shun-Guang Lamb, Fred S. Shears, Stephen B. TI Functional Regulation of ClC-3 in the Migration of Vascular Smooth Muscle 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 [Ganapathi, Sindura B.; Shears, Stephen B.] NIEHS, Res Triangle Pk, NC 27709 USA. [Wei, Shun-Guang] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Lamb, Fred S.] Vanderbilt Univ, Nashville, TN 37235 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 549A EP 549A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561203661 ER PT J AU Sunyer, R Jin, AJ Nossal, R Sackett, DL AF Sunyer, Raimon Jin, Albert J. Nossal, Ralph Sackett, Dan L. TI Fabrication of Hydrogels with Gradient of Compliance: Application to Cell Mechanotaxis and Durotaxis 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 [Sunyer, Raimon; Jin, Albert J.; Nossal, Ralph; Sackett, Dan L.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 565A EP 565A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204033 ER PT J AU Wu, ZH Plotnikov, S Waterman, CM Liu, J AF Wu, Zhanghan Plotnikov, Sergey Waterman, Clare M. Liu, Jian TI A Mechanochemistry Model of Focal Adhesion Dynamics in Cell Migration 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 [Wu, Zhanghan; Plotnikov, Sergey; Waterman, Clare M.; Liu, Jian] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 8 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 566A EP 566A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204037 ER PT J AU Swenson, AM Trivedi, D Takagi, Y Sellers, JR Yengo, CM AF Swenson, Anja M. Trivedi, Darshan Takagi, Yasuharu Sellers, James R. Yengo, Christopher M. TI Differential Impact of Temperature and Magnesium on Myosin V and Myosin II 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 [Swenson, Anja M.] Gustavus Adolphus Coll, St Peter, MN 56082 USA. [Trivedi, Darshan; Yengo, Christopher M.] Penn State Univ, Coll Med, Hershey, PA USA. [Takagi, Yasuharu; Sellers, James R.] NHLBI, NIH, Bethesda, MD 20892 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 567A EP 567A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204043 ER PT J AU Bond, LM Kendrick-Jones, J Buss, F Sellers, JR AF Bond, Lisa M. Kendrick-Jones, John Buss, Folma Sellers, James R. TI Examination of the Kinetics of Myosin VI during Endocytosis 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 [Bond, Lisa M.] Univ Cambridge, NIH, Bethesda, MD USA. [Kendrick-Jones, John] MRC, Mol Biol Lab, Cambridge CB2 2QH, England. [Buss, Folma] Univ Cambridge, Cambridge, England. [Sellers, James R.] NIH, Bethesda, MD 20892 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 569A EP 569A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204056 ER PT J AU Maldonado, EN DeHart, DN Patnaik, JR Sheldon, KL Rostovtseva, TK Manevich, Y Townsend, D Lemasters, JJ AF Maldonado, Eduardo N. DeHart, David N. Patnaik, Jyoti R. Sheldon, Kely L. Rostovtseva, Tatiana K. Manevich, Yefim Townsend, Danyelle Lemasters, John J. TI Voltage Dependent Anion Channel-3 (VDAC3) is the Major Isoform Contributing to Mitochondrial Metabolism in HepG2 Cells and is Regulated by Free Tubulin and Erastin 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 [Maldonado, Eduardo N.; DeHart, David N.; Patnaik, Jyoti R.; Lemasters, John J.] Med Univ S Carolina, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Maldonado, Eduardo N.; DeHart, David N.; Patnaik, Jyoti R.; Manevich, Yefim; Townsend, Danyelle; Lemasters, John J.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Sheldon, Kely L.; Rostovtseva, Tatiana K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Sheldon, Kely L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, W Harry Feinstein Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Lemasters, John J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 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 573A EP 573A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204072 ER PT J AU Connelly, LS Arce, FT Jang, H Capone, R Kotler, S Kagan, B Nussinov, R Lal, R AF Connelly, Laura S. Arce, Fernando Teran Jang, Hyunbum Capone, Ricardo Kotler, Samuel Kagan, Bruce Nussinov, Ruth Lal, Ratnesh TI Alzheimer's beta-Amyloid All-D-Enantiomers and Native All-L-Enantiomers Exhibit Similar Pore Structures in Lipid Bilayers: Atomic Force Microscopy 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 [Connelly, Laura S.; Arce, Fernando Teran; Capone, Ricardo; Kotler, Samuel; Lal, Ratnesh] Univ Calif San Diego, San Diego, CA 92103 USA. [Jang, Hyunbum; Nussinov, Ruth] SAIC Frederick Inc, Ctr Canc Res, Nanobiol Program, NCI Frederick, Frederick, MD USA. [Kagan, Bruce] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Dept Psychiat, Los Angeles, CA 90095 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Human Mol Genet & Biochem 4Dept, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 2 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 588A EP 589A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204156 ER PT J AU Chaurasiya, KR Geertsema, H Qualley, DF Wu, TY Iwatani, Y Chan, D Hertz, A Levin, JG Musier-Forsyth, K Rouzina, I Williams, MC AF Chaurasiya, Kathy R. Geertsema, Hylkje Qualley, Dominic F. Wu, Tiyun Iwatani, Yasumasa Chan, Denise Hertz, Amber Levin, Judith G. Musier-Forsyth, Karin Rouzina, Ioulia Williams, Mark C. TI Oligomerization of HIV-1 Restriction Factor APOBEC3G Transforms it from a Fast Enzyme to a Slow Nucleic Acid Binding Protein 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 [Chaurasiya, Kathy R.; Geertsema, Hylkje; Williams, Mark C.] Northeastern Univ, Boston, MA 02115 USA. [Qualley, Dominic F.; Musier-Forsyth, Karin] Ohio State Univ, Columbus, OH 43210 USA. [Wu, Tiyun; Iwatani, Yasumasa; Hertz, Amber; Levin, Judith G.] NIH, Bethesda, MD 20892 USA. [Iwatani, Yasumasa] Natl Hosp Org Nagoya Med Ctr, Nagoya, Aichi, Japan. [Chan, Denise] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Rouzina, Ioulia] Univ Minnesota, Minneapolis, MN 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 601A EP 601A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204217 ER PT J AU Bhatnagar, J Sim, HM Georgieva, E Kapoor, K Chufan, E Ohnuma, S Borbat, PP Freed, JH Sauna, ZE Ambudkar, SV AF Bhatnagar, Jaya Sim, Hong-May Georgieva, Elka Kapoor, Khyati Chufan, Eduardo Ohnuma, Shinobu Borbat, Peter P. Freed, Jack H. Sauna, Zuben E. Ambudkar, Suresh V. TI Mapping Conformational Changes Associated with the Catalytic Cycle of Human P-Glycoprotein (ABCB1) 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 [Bhatnagar, Jaya; Sim, Hong-May; Kapoor, Khyati; Chufan, Eduardo; Ohnuma, Shinobu; Ambudkar, Suresh V.] NCI, NIH, Bethesda, MD 20892 USA. [Georgieva, Elka; Borbat, Peter P.; Freed, Jack H.] Cornell Univ, Natl Biomed Ctr Adv ESR Technol, ACERT, Ithaca, NY USA. [Sauna, Zuben E.] US FDA, Div Hematol, CBER, Bethesda, MD 20014 USA. RI Borbat, Petr/A-8658-2014; borbat, peter/B-1616-2016 NR 0 TC 0 Z9 0 U1 0 U2 3 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 606A EP 607A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204245 ER PT J AU Sandtner, W Egwolf, B Khalili-Araghi, F Sanchez-Rodriguez, JE Roux, B Bezanilla, F Holmgren, M AF Sandtner, Walter Egwolf, Bernhard Khalili-Araghi, Fatemeh Sanchez-Rodriguez, Jorge E. Roux, Benoit Bezanilla, Francisco Holmgren, Miguel TI Ouabain Binding Site in a Functioning Na plus /K plus -ATPase 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 [Sandtner, Walter] Med Univ Vienna, Vienna, Austria. [Egwolf, Bernhard] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany. [Khalili-Araghi, Fatemeh; Sanchez-Rodriguez, Jorge E.; Roux, Benoit; Bezanilla, Francisco] Univ Chicago, Chicago, IL 60637 USA. [Holmgren, Miguel] NIH, Bethesda, MD 20892 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 607A EP 607A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204246 ER PT J AU Capone, R Jang, H Kotler, SA Connelly, L Williams, M Reddy, SR Kagan, BL Nussinov, R Lal, R AF Capone, Ricardo Jang, Hyunbum Kotler, Samuel A. Connelly, Laura Williams, Michael Reddy, Srinivasan Ramachandra Kagan, Bruce L. Nussinov, Ruth Lal, Ratnesh TI All D-Amino Acids Amyloid beta Forms Ion Channels in Lipid Bilayers and is Toxic to 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 [Capone, Ricardo; Kotler, Samuel A.; Connelly, Laura; Reddy, Srinivasan Ramachandra; Lal, Ratnesh] UCSD, Dept Bioengn, La Jolla, SD USA. [Capone, Ricardo; Kotler, Samuel A.; Connelly, Laura; Reddy, Srinivasan Ramachandra; Lal, Ratnesh] UCSD, Dept Mech & Aerosp Engn, La Jolla, SD USA. [Jang, Hyunbum; Nussinov, Ruth] SAIC Frederick, Ctr Canc Res, Natl Canc Inst, Nanobiol Program, Frederick, MD USA. [Williams, Michael] Univ Calif San Diego, IMSD Program, La Jolla, SD USA. [Kagan, Bruce L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 2 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 616A EP 617A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204293 ER PT J AU Carter, M Voth, A Ho, S AF Carter, Megan Voth, Andrea Ho, Shing TI Structure-Energy Relationship of Biological Halogen Bonds: Development of Anisotropic Force Fields 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 [Carter, Megan; Ho, Shing] Colorado State Univ, Ft Collins, CO 80523 USA. [Voth, Andrea] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 620A EP 620A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204308 ER PT J AU Emileh, A Tuzer, F Moreira, DR LaLonde, JM Bewley, CA Chaiken, IM Abrams, CF AF Emileh, Ali Tuzer, Ferit Moreira, Diogo R. LaLonde, Judith M. Bewley, Carole A. Chaiken, Irwin M. Abrams, Cameron F. TI A Molecular Dynamics Simulation of Peptide-Triazole HIV Entry Inhibitor Binding to gp120 Hydrophobic Core 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 [Emileh, Ali; Abrams, Cameron F.] Drexel Univ, Philadelphia, PA 19104 USA. [Emileh, Ali; Tuzer, Ferit; Moreira, Diogo R.; Chaiken, Irwin M.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [LaLonde, Judith M.] Bryn Mawr Coll, Bryn Mawr, PA 19010 USA. [Bewley, Carole A.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 4 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 621A EP 621A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204314 ER PT J AU Lee, KI McLaughlin, SG Im, W Pastor, RW AF Lee, Kyu Il McLaughlin, Stuart G. Im, Wonpil Pastor, Richard W. TI Langevin Dynamics Simulations of Protein Fencing of PIP2 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 [Lee, Kyu Il; Im, Wonpil] Univ Kansas, Lawrence, KS 66045 USA. [McLaughlin, Stuart G.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Pastor, Richard W.] NIH, Bethesda, MD 20892 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 624A EP 624A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204329 ER PT J AU Ball, KA Phillips, AH Fawzi, NL Wemmer, DE Head-Gordon, T AF Ball, K. Aurelia Phillips, Aaron H. Fawzi, Nicolas L. Wemmer, David E. Head-Gordon, Teresa TI Amyloid-Beta Heterogeneous Conformational Ensembles: Differences Between the 40-and 42-Residue Peptides and Implications for Dimer Polyamorphism 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 [Ball, K. Aurelia; Phillips, Aaron H.; Wemmer, David E.; Head-Gordon, Teresa] Univ Calif Berkeley, Berkeley, CA USA. [Fawzi, Nicolas L.] NIH, Bethesda, MD 20892 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 631A EP 631A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204365 ER PT J AU Tolchard, JL Eaglen, LA Morris, L Hackstadt, T Blumenschein, TM AF Tolchard, James L. Eaglen, Lawrence A. Morris, Leah Hackstadt, Ted Blumenschein, Tharin M. TI Insights into the Dynamics and Actin Interaction of the Intrinsically Disordered Tarp Protein from Chlamydia 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 [Tolchard, James L.; Eaglen, Lawrence A.; Morris, Leah; Blumenschein, Tharin M.] Univ E Anglia, Norwich NR4 7TJ, Norfolk, England. [Hackstadt, Ted] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. RI Tolchard, Julian/B-7889-2010 OI Tolchard, Julian/0000-0003-0934-4515 NR 0 TC 0 Z9 0 U1 3 U2 7 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 634A EP 634A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204378 ER PT J AU Kim, T Afonin, K Heldman, E Blumenthal, R Shapiro, B AF Kim, Taejin Afonin, Kirill Heldman, Eliahu Blumenthal, Robert Shapiro, Bruce TI In Silico and in Ex-Vivo Experiments Indicate the Potential of Nanoparticles Composed of RNA-Bolaamphiphile Complexes as a Therapeutic siRNA Delivery Vehicle 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 [Kim, Taejin; Afonin, Kirill; Heldman, Eliahu; Blumenthal, Robert; Shapiro, Bruce] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 638A EP 638A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204399 ER PT J AU Ivanov, V Mizuuchi, K AF Ivanov, Vassili Mizuuchi, Kiyoshi TI Alternating Two Different Diffusion States of Min Proteins on the Lipid Bilayer Revealed by Single Molecule Tracking 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 [Ivanov, Vassili; Mizuuchi, Kiyoshi] NIDDK, NIH, Bethesda, MD 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 652A EP 652A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204474 ER PT J AU Simakova, O Arispe, NJ AF Simakova, Olga Arispe, Nelson J. TI Phosphatidyl-Serine-Positive Cells with High Sensitivity to the Alzheimer's Disease A beta Peptides Display Distinctive Mitochondrial Characteristics 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 [Simakova, Olga] NIH, Bethesda, MD 20892 USA. [Arispe, Nelson J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 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 657A EP 657A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204497 ER PT J AU Sirenko, S Vinogradova, TM Maltsev, V Lakatta, EG AF Sirenko, Syevda Vinogradova, Tatiana M. Maltsev, Victor Lakatta, Edward G. TI An Inherent Ability of Ventricular Myocytes to Self-Organize Spontaneous RyRs Activation that Generate Synchronized Local Ca2+ Releases is Physiologically Suppressed by Constitutive Phosphodiesterase and Protein Phosphatase Activity 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 [Sirenko, Syevda; Vinogradova, Tatiana M.; Maltsev, Victor; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 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 671A EP 672A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204573 ER PT J AU Yaniv, Y Spurgeon, HA Ziman, BD Lakatta, EG AF Yaniv, Yael Spurgeon, Harold A. Ziman, Bruce D. Lakatta, Edward G. TI Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII) Activity Modulates Sinoatrial Nodal Pacemaker Cell Energetics 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 [Yaniv, Yael; Spurgeon, Harold A.; Ziman, Bruce D.; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 USA. RI Yaniv, Yael/B-3311-2015 OI Yaniv, Yael/0000-0002-5183-6284 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 671A EP 671A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204572 ER PT J AU Maltsev, VA Yaniv, Y Lakatta, EG AF Maltsev, Victor A. Yaniv, Yael Lakatta, Edward G. TI Numerical Modeling of Flash-Induced Ca2+ Release in Sa Node Cells (SANC) Supports the "Coupled-Clock'' Hypothesis of Cardiac Pacemaker Cell Function 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 [Maltsev, Victor A.; Yaniv, Yael; Lakatta, Edward G.] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RI Yaniv, Yael/B-3311-2015 OI Yaniv, Yael/0000-0002-5183-6284 NR 0 TC 0 Z9 0 U1 0 U2 3 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 673A EP 673A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204578 ER PT J AU Yang, DM Zahanich, I Lyashkov, AE Lakatta, EG AF Yang, Dongmei Zahanich, Ihor Lyashkov, Alexey E. Lakatta, Edward G. TI Action Potential (AP) Cycle Length in Connexin-43-Negative and Positive Single Isolated Sinoatrial Node Cells (SANC) does not Differ in the Basal State or during High-Level Beta-AR Stimulation 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, Dongmei; Zahanich, Ihor; Lyashkov, Alexey E.; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 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 674A EP 675A PG 2 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204586 ER PT J AU Krepkiy, D Gawrisch, K Swartz, KJ AF Krepkiy, Dmitriy Gawrisch, Klaus Swartz, Kenton J. TI Protein- Lipid Interactions in Lipid Reconstituted Potassium Channel Voltage-Sensing Domains 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 [Krepkiy, Dmitriy; Gawrisch, Klaus; Swartz, Kenton J.] NIH, Bethesda, MD 20892 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 685A EP 685A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204635 ER PT J AU Smith, JJ AF Smith, Jaime J. TI Characterization of a Novel Voltage-Sensing Protein 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 [Smith, Jaime J.] NINDS, NIH, Bethesda, MD 20892 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 685A EP 685A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204636 ER PT J AU Miranda, P Contreras, JE Wesch, D Sigworth, FJ Holmgren, M Giraldez, T AF Miranda, Pablo Contreras, Jorge E. Wesch, Diana Sigworth, Fred J. Holmgren, Miguel Giraldez, Teresa TI State-Dependent FRET Reports Large Gating-Ring Motions in BK Channels 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 [Miranda, Pablo; Wesch, Diana; Giraldez, Teresa] Univ Hosp NS Candelaria, Div Res, Tenerife, Spain. [Miranda, Pablo; Wesch, Diana] Univ La Laguna, Dept Physiol, Tenerife, Spain. [Contreras, Jorge E.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Sigworth, Fred J.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Holmgren, Miguel] NINDS, NIH, Bethesda, MD 20892 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 687A EP 687A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204647 ER PT J AU Chen, J Lippicott-Schwartz, J Liu, J AF Chen, Jing Lippicott-Schwartz, Jennifer Liu, Jian TI Intracellular Spatial Localization Regulated by the Microtubule Network 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 [Chen, Jing; Lippicott-Schwartz, Jennifer; Liu, Jian] NIH, Bethesda, MD 20892 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 698A EP 698A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561204700 ER PT J AU Hung, SH Arce, SH Wu, PH Tseng, Y AF Hung, Shen-Hsiu Arce, Stephen Hugo Wu, Pei-Hsun Tseng, Yiider TI A Biophysical Analysis of Cell and Nucleus Relation 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 [Hung, Shen-Hsiu; Arce, Stephen Hugo; Wu, Pei-Hsun; Tseng, Yiider] Univ Flordia, Dept Chem Engn, Gainseville, FL USA. [Hung, Shen-Hsiu; Wu, Pei-Hsun; Tseng, Yiider] NCI, Phys Sci Oncol Ctr, Gainesville, FL 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 707A EP 707A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561205044 ER PT J AU Holmgren, M Gadsby, DC Bezanilla, F Rakowski, RF De Weer, P AF Holmgren, Miguel Gadsby, David C. Bezanilla, Francisco Rakowski, Robert F. De Weer, Paul TI Na+ Access Kinetics in the Na+/K+-Atpase Pump 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 [Holmgren, Miguel] NIH, Bethesda, MD 20892 USA. [Gadsby, David C.; Bezanilla, Francisco; Rakowski, Robert F.; De Weer, Paul] Marine Biol Lab, Woods Hole, MA 02543 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 708A EP 708A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561205050 ER PT J AU Sanchez-Rodriguez, JE Khalili-Araghi, F Roux, B Holmgren, M Bezanilla, F AF Sanchez-Rodriguez, Jorge E. Khalili-Araghi, Fatemeh Roux, Benoit Holmgren, Miguel Bezanilla, Francisco TI Changes of Intramolecular Distances in the Na+/K+ Atpase upon Ouabain Binding 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 [Sanchez-Rodriguez, Jorge E.; Khalili-Araghi, Fatemeh; Roux, Benoit; Bezanilla, Francisco] Univ Chicago, Dept Biochem & Mol Biol, Gordon Ctr Integrat Sci, Chicago, IL 60637 USA. [Holmgren, Miguel] NINDS, Mol Neurophysiol Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 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 708A EP 708A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561205049 ER PT J AU Chandran, PL Dimitriadis, EK Horkay, F AF Chandran, Preethi L. Dimitriadis, Emilios K. Horkay, Ferenc TI Structure, Assembly and Mechanical Properties of DNA Nanoparticles Condensed with Peim 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 [Chandran, Preethi L.] NIH, Bethesda, MD 20892 USA. [Dimitriadis, Emilios K.] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA. [Horkay, Ferenc] NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 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 719A EP 719A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561205103 ER PT J AU Sarkar, SK Bumb, A Wu, XFS Brechbiel, MW Neuman, KC AF Sarkar, Susanta K. Bumb, Ambika Wu, Xufeng S. Brechbiel, Martin W. Neuman, Keir C. TI Quantitative Characterization of Dyes Embedded in Nanoparticles by Single-Molecule Fluorescence 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 [Sarkar, Susanta K.; Bumb, Ambika; Wu, Xufeng S.; Brechbiel, Martin W.; Neuman, Keir C.] NIH, Bethesda, MD 20892 USA. RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 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 725A EP 725A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561205136 ER PT J AU Balijepalli, A Lee, KI Im, W Pastor, RW AF Balijepalli, Arvind Lee, Kyu Il Im, Wonpil Pastor, Richard W. TI Modeling Polymer Interactions with Nanopores for DNA Sequencing and Proteomics Applications 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 [Balijepalli, Arvind; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Balijepalli, Arvind] NIST, Div Semicond Elect, Phys Measurement Lab, Gaithersburg, MD 20899 USA. [Lee, Kyu Il; Im, Wonpil] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA. [Lee, Kyu Il; Im, Wonpil] Univ Kansas, Ctr Bioinformat, Lawrence, KS 66045 USA. NR 0 TC 0 Z9 0 U1 0 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 732A EP 732A PG 1 WC Biophysics SC Biophysics GA 179ZF UT WOS:000321561205170 ER PT J AU Diesner, SC Olivera, A Dillahunt, S Schultz, C Watzlawek, T Forster-Waldl, E Pollak, A Jensen-Jarolim, E Untersmayr, E Rivera, J AF Diesner, Susanne C. Olivera, Ana Dillahunt, Sandra Schultz, Cornelia Watzlawek, Thomas Foerster-Waldl, Elisabeth Pollak, Arnold Jensen-Jarolim, Erika Untersmayr, Eva Rivera, Juan TI Sphingosine-kinase 1 and 2 contribute to oral sensitization and effector phase in a mouse model of food allergy SO IMMUNOLOGY LETTERS LA English DT Article DE Sphingosine-1-phosphate; Food allergy; Sphingosine kinase; Mast cells; Anti-ulcer medication; Ovalbumin ID MAST-CELLS; BARRIER FUNCTION; SPHINGOSINE-1-PHOSPHATE; 1-PHOSPHATE; RECEPTORS; ANAPHYLAXIS; SUPPRESSION; PROTEINS; ASTHMA; MICE AB Background: Sphingosine-1-phosphate (S1P) influences activation, migration and death of immune cells. Further, S1P was proposed to play a major role in the induction and promotion of allergic diseases. However, to date only limited information is available on the role of S1P in food allergy. Objective: We aimed to investigate the role of sphingosine-kinase (SphK) 1 and 2, the enzymes responsible for endogenous S1P production, on the induction of food allergy. Methods and results: Human epithelial colorectal CaCo2 cells stimulated in vitro with S1P revealed a decrease of transepithelial resistance and enhanced transport of FITC labeled OVA. We studied the effect of genetic deletion of the enzymes involved in S1P production on food allergy induction using a mouse model of food allergy based on intragastrically (i.g.) administered ovalbumin (OVA) with concomitant acid-suppression. Wild-type (WT), SphK1(-/-) and SphK2(-/-) mice immunized with OVA alone i.g. or intraperitoneally (i.p.) were used as negative or positive controls, respectively. SphK1- and SphK2-deficient mice fed with OVA under acid-suppression showed reduced induction of OVA specific IgE and IgG compared to WT mice, but had normal responses when immunized by the intraperitoneal route. Flow cytometric analysis of spleen cells revealed a significantly reduced proportion of CD4(+) effector T-cells in both SphK deficient animals after oral sensitization. This was accompanied by a reduced accumulation of mast cells in the gastric mucosa in SphK-deficient animals compared to WT mice. Furthermore, mouse mast cell protease-1 (mMCP-1) levels, an IgE-mediated anaphylaxis marker, were reliably elevated in allergic WT animals. Conclusion: Modulation of the S1P homeostasis by deletion of either SphK1 or SphK2 alters the sensitization and effector phase of food allergy. (C) 2011 Elsevier B.V. All rights reserved. C1 [Diesner, Susanne C.; Schultz, Cornelia; Watzlawek, Thomas; Jensen-Jarolim, Erika; Untersmayr, Eva] Med Univ Vienna, Ctr Pathophysiol Infectiol & Immunol, Dept Pathophysiol & Allergy Res, A-1090 Vienna, Austria. [Diesner, Susanne C.; Foerster-Waldl, Elisabeth; Pollak, Arnold] Med Univ Vienna, Dept Pediat & Adolescent Med, A-1090 Vienna, Austria. [Diesner, Susanne C.; Olivera, Ana; Dillahunt, Sandra; Rivera, Juan] NIAMS, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA. [Jensen-Jarolim, Erika] Univ Vienna, Messerli Inst Med Univ Vienna, A-1090 Vienna, Austria. [Jensen-Jarolim, Erika] Vet Univ Vienna, A-1090 Vienna, Austria. RP Untersmayr, E (reprint author), Med Univ Vienna, Ctr Pathophysiol Infectiol & Immunol, Dept Pathophysiol & Allergy Res, Waehringer Guertel 18-20,E3Q, A-1090 Vienna, Austria. EM eva.untersmayr@meduniwien.ac.at; juan_rivera@nih.gov FU NIAMS, NIH; Austrian Science fund FWF [P21577, P21884]; European Molecular Biology Organization (EMBO) [ASTF 374-2008]; Flow Cytometry Section, Laboratory Animal Care and Use Section, and the Light Imaging Section, of the Office of Science and Technology, NIAMS FX This work was supported by the Intramural Research Program of NIAMS, NIH and grants of the Austrian Science fund FWF (P21577 and P21884). Susanne C. Diesner was supported by a short-term fellowship (ASTF 374-2008) of the European Molecular Biology Organization (EMBO). We also acknowledge the support of the Flow Cytometry Section, Laboratory Animal Care and Use Section, and the Light Imaging Section, of the Office of Science and Technology, NIAMS and Dr. Sonja Zehetmayer for statistical advise in data presentation. NR 42 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JAN 30 PY 2012 VL 141 IS 2 BP 210 EP 219 DI 10.1016/j.imlet.2011.10.006 PG 10 WC Immunology SC Immunology GA 900AR UT WOS:000300859500009 PM 22020265 ER PT J AU Jacobson, O Weiss, ID Szajek, LP Niu, G Ma, Y Kiesewetter, DO Peled, A Eden, HS Farber, JM Chen, XY AF Jacobson, Orit Weiss, Ido D. Szajek, Lawrence P. Niu, Gang Ma, Ying Kiesewetter, Dale O. Peled, Amnon Eden, Henry S. Farber, Joshua M. Chen, Xiaoyuan TI Improvement of CXCR4 tracer specificity for PET imaging SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE T140; CXCR4 imaging; PET; Copper-64 ID CHEMOKINE RECEPTORS; BONE-MARROW; CELL MOBILIZATION; CANCER METASTASIS; G-CSF; TUMOR; EXPRESSION; MICROENVIRONMENT; ANTAGONIST; XENOGRAFTS AB Tumors expressing the chemokine receptor CXCR4 have been reported to be more aggressive and to produce more metastatic seeding in specific organs, such as the bone marrow. However, evaluation of tumors for CXCR4 expression requires testing of ex vivo biopsy samples, and is not routinely done in cancer management. In prior work to address this issue, we and others have developed tracers for positron emission tomography (PET) that targeted CXCR4, but in addition to binding to CXCR4 these tracers also bound to red blood cells (and to other unrelated targets) in vivo. Here we report two new tracers based on the CXCR4 peptide antagonist 4F-benzoyl-TN14003 (T140) that bind to CXCR4, but not to undesired targets. These tracers, NOTA-NFB and DOTA-NFB, show slight reductions in both 1) binding affinities for CXCR4 and 2) inhibition of CXCL12 induced migration, compared to T140, in vitro. Both NOTA-NFB and DOTA-NFB specifically accumulate in CXCR4-positive, but not CXCR4-negative, tumor xenografts in mice and allow clear visualization of CXCR4 expression by PET. Evaluation of NOTA-NFB and DOTA-NFB for their potential to mobilize immune cells and progenitor cells from the bone marrow to the peripheral blood revealed slightly reduced, but still comparable, results to the parent molecule T140. The tracers reported here may allow the evaluation of CXCR4 expression in primary tumors and metastatic nodules, and enable better informed, more personalized treatment for patients with cancer. Published by Elsevier B.V. C1 [Jacobson, Orit; Niu, Gang; Ma, Ying; Kiesewetter, Dale O.; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Weiss, Ido D.; Farber, Joshua M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Szajek, Lawrence P.] NIH, Warren Grant Magnuson Clin Ctr, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA. [Peled, Amnon] Hadassah Hebrew Univ Hosp, Goldyne Savad Inst Gene Therapy, Jerusalem, Israel. [Eden, Henry S.] NIBIB, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bldg 31,Room 1C22, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov FU National Institute of Biomedical Imaging and Bioengineering (NIBIB); National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); National Science Foundation of China (NSFC) [81028009] FX This research was supported in part by the Intramural Research Programs (IRPs) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and by the International Cooperative Program of the National Science Foundation of China (NSFC) (81028009). NR 35 TC 19 Z9 19 U1 0 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD JAN 30 PY 2012 VL 157 IS 2 BP 216 EP 223 DI 10.1016/j.jconrel.2011.09.076 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 902NO UT WOS:000301045400007 PM 21964282 ER PT J AU Simons, SS Chow, CC AF Simons, S. Stoney, Jr. Chow, Carson C. TI The road less traveled: New views of steroid receptor action from the path of dose-response curves SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Review DE Steroid hormone action; Potency (EC50); Efficacy (A(max)); Partial agonist activity (PAA); New insight for steroid receptor mechanism ID LIGAND-BINDING DOMAIN; GLUCOCORTICOID-RECEPTOR; GENE-EXPRESSION; NUCLEAR RECEPTOR; COACTIVATOR BINDING; INDUCTION PROPERTIES; ANDROGEN RECEPTOR; TRANSCRIPTION; TRANSACTIVATION; PROMOTER AB Conventional studies of steroid hormone action proceed via quantitation of the maximal activity for gene induction at saturating concentrations of agonist steroid (i.e., A(max)). Less frequently analyzed parameters of receptor-mediated gene expression are EC50 and PAA. The EC50 is the concentration of steroid required for half-maximal agonist activity and is readily determined from the dose-response curve. The PAA is the partial agonist activity of an antagonist steroid, expressed as percent of A(max) under the same conditions. Recent results demonstrate that new and otherwise inaccessible mechanistic information is obtained when the EC50 and/or PAA are examined in addition to the A(max). Specifically, A(max), EC50, and PAA can be independently regulated, which suggests that novel pathways and factors may preferentially modify the EC50 and/or PAA with little effect on A(max). Other approaches indicate that the activity of receptor-bound factors can be altered without changing the binding of factors to receptor. Finally, a new theoretical model of steroid hormone action not only permits a mechanistically based definition of factor activity but also allows the positioning of when a factor acts, as opposed to binds, relative to a kinetically defined step. These advances illustrate some of the benefits of expanding the mechanistic studies of steroid hormone action to routinely include EC50 and PAA. Published by Elsevier Ireland Ltd. C1 [Simons, S. Stoney, Jr.] NIDDK, Steroid Hormones Sect, CEB, NIH, Bethesda, MD 20892 USA. [Chow, Carson C.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, Steroid Hormones Sect, CEB, NIH, Bldg 10,Room 8N-307B, Bethesda, MD 20892 USA. EM steroids@helix.nih.gov RI Chow, Carson/A-7970-2009 FU NIH, NIDDK FX We thank members of the Steroid Hormones Section for valuable comments and insight. This research was supported by the Intramural Research Program of the NIH, NIDDK. NR 47 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 30 PY 2012 VL 348 IS 2 SI SI BP 373 EP 382 DI 10.1016/j.mce.2011.05.030 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 891BF UT WOS:000300190500004 PM 21664235 ER PT J AU Conway-Campbell, BL Pooley, JR Hager, GL Lightman, SL AF Conway-Campbell, Becky L. Pooley, John R. Hager, Gordon L. Lightman, Stafford L. TI Molecular dynamics of ultradian glucocorticoid receptor action SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Review DE Glucocorticoid receptor; Ultradian; Transcription; CBP; P300; Acetylation ID PITUITARY-ADRENAL AXIS; LIGAND-SPECIFIC DYNAMICS; TARGET GENE PROMOTERS; ESTROGEN-RECEPTOR; LIVING CELLS; HISTONE ACETYLATION; IN-VIVO; STRESS RESPONSIVENESS; ANDROGEN RECEPTOR; FEMALE RATS AB In recent years it has become evident that glucocorticoid receptor (GR) action in the nucleus is highly dynamic, characterized by a rapid exchange at the chromatin template. This stochastic mode of GR action couples perfectly with a deterministic pulsatile availability of endogenous ligand in vivo. The endogenous glucocorticoid hormone (cortisol in man and corticosterone in rodent) is secreted from the adrenal gland with an ultradian rhythm made up of pulses at approximately hourly intervals. These two components the rapidly fluctuating ligand and the rapidly exchanging receptor - appear to have evolved to establish and maintain a system that is exquisitely responsive to the physiological demands of the organism. In this review, we discuss recent and innovative work that questions the idea of steady state, static hormone receptor responses, and replaces them with new concepts of stochastic mechanisms and oscillatory activity essential for optimal function in molecular and cellular systems. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Conway-Campbell, Becky L.; Pooley, John R.; Lightman, Stafford L.] Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Bristol BS1 3NY, Avon, England. [Pooley, John R.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Conway-Campbell, BL (reprint author), Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Dorothy Hodgkin Bldg,Whitson St, Bristol BS1 3NY, Avon, England. EM b.conway-campbell@bristol.ac.uk FU Medical Research Council [MR/J008893/1] NR 119 TC 25 Z9 28 U1 0 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 30 PY 2012 VL 348 IS 2 SI SI BP 383 EP 393 DI 10.1016/j.mce.2011.08.014 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 891BF UT WOS:000300190500005 PM 21872640 ER PT J AU Albert, PS AF Albert, Paul S. TI A linear mixed model for predicting a binary event from longitudinal data under random effects misspecification SO STATISTICS IN MEDICINE LA English DT Article DE longitudinal data; prediction; random effects distribution ID MAXIMUM-LIKELIHOOD ESTIMATION; GROWTH AB The use of longitudinal data for predicting a subsequent binary event is often the focus of diagnostic studies. This is particularly important in obstetrics, where ultrasound measurements taken during fetal development may be useful for predicting various poor pregnancy outcomes. We propose a modeling framework for predicting a binary event from longitudinal measurements where a shared random effect links the two processes together. Under a Gaussian random effects assumption, the approach is simple to implement with standard statistical software. Using asymptotic and simulation results, we show that estimates of predictive accuracy under a Gaussian random effects distribution are robust to severe misspecification of this distribution. However, under some circumstances, estimates of individual risk may be sensitive to severe random effects misspecification. We illustrate the methodology with data from a longitudinal fetal growth study. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. EM albertp@mail.nih.gov FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX I thank the associate editor and two reviewers for their constructive comments on this article. I also thank Dr. Jun Zhang for the helpful comments on this manuscript and the Center for Information Technology, National Institutes of Health, for providing access to the high-performance computational capabilities of the Biowulf cluster computer system. The Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development supported this research. NR 24 TC 8 Z9 8 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2012 VL 31 IS 2 BP 143 EP 154 DI 10.1002/sim.4405 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 869JY UT WOS:000298595400004 PM 22081439 ER PT J AU Lee, KI Jo, S Rui, H Egwolf, B Roux, B Pastor, RW Im, W AF Lee, Kyu Il Jo, Sunhwan Rui, Huan Egwolf, Bernhard Roux, Benoit Pastor, Richard W. Im, Wonpil TI Web interface for brownian dynamics simulation of ion transport and its applications to beta-barrel pores SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article DE grand canonical Monte Carlo; Brownian dynamics; channel conductance; ion selectivity; voltage dependent anion channel; a-hemolysin; anthrax toxin protective antigen pore ID STAPHYLOCOCCAL ALPHA-HEMOLYSIN; NONCOVALENT MOLECULAR ADAPTER; PROTECTIVE ANTIGEN; ELECTRODIFFUSION THEORY; OMPF PORIN; CHANNEL; PERMEATION; CYCLODEXTRIN; SELECTIVITY; ANTHRAX AB Brownian dynamics (BD) based on accurate potential of mean force is an efficient and accurate method for simulating ion transport through wide ion channels. Here, a web-based graphical user interface (GUI) is presented for carrying out grand canonical Monte Carlo (GCMC) BD simulations of channel proteins: . The webserver is designed to help users avoid most of the technical difficulties and issues encountered in setting up and simulating complex pore systems. GCMC/BD simulation results for three proteins, the voltage dependent anion channel (VDAC), a-Hemolysin (a-HL), and the protective antigen pore of the anthrax toxin (PA), are presented to illustrate the system setup, input preparation, and typical output (conductance, ion density profile, ion selectivity, and ion asymmetry). Two models for the input diffusion constants for potassium and chloride ions in the pore are compared: scaling of the bulk diffusion constants by 0.5, as deduced from previous all-atom molecular dynamics simulations of VDAC, and a hydrodynamics based model (HD) of diffusion through a tube. The HD model yields excellent agreement with experimental conductances for VDAC and a-HL, while scaling bulk diffusion constants by 0.5 leads to underestimates of 1020%. For PA, simulated ion conduction values overestimate experimental values by a factor of 1.57 (depending on His protonation state and the transmembrane potential), implying that the currently available computational model of this protein requires further structural refinement. (C) 2011 Wiley Periodicals, Inc. J Comput Chem, 2012 C1 [Lee, Kyu Il; Jo, Sunhwan; Rui, Huan; Im, Wonpil] Univ Kansas, Ctr Bioinformat, Lawrence, KS 66045 USA. [Lee, Kyu Il; Jo, Sunhwan; Rui, Huan; Im, Wonpil] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA. [Egwolf, Bernhard] Max Planck Inst Biophys Chem, Dept Theoret & Computat Biophys, Gottingen, Germany. [Roux, Benoit] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. [Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Lee, KI (reprint author), Univ Kansas, Ctr Bioinformat, Lawrence, KS 66045 USA. EM wonpil@ku.edu FU University of Kansas [2301388-003]; Kansas-COBRE NIH [P20 RR-17708]; National Science Foundation [NSF OCI-0503992]; NIH [GM062342]; German Research Foundation; National Heart, Lung, and Blood Institute in the National Institutes of Health FX Contract grant sponsor: University of Kansas General Research Fund allocation; Contract grant number: 2301388-003; Contract grant sponsor: Kansas-COBRE NIH; Contract grant number: P20 RR-17708; Contract grant sponsor: National Science Foundation (TeraGrid resources provided by Purdue University); Contract grant number: NSF OCI-0503992; Contract grant sponsor: NIH; Contract grant number: GM062342; Contract grant sponsors: German Research Foundation; Intramural Research Program of the National Heart, Lung, and Blood Institute in the National Institutes of Health NR 43 TC 23 Z9 23 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD JAN 30 PY 2012 VL 33 IS 3 BP 331 EP 339 DI 10.1002/jcc.21952 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 861ZA UT WOS:000298058400011 PM 22102176 ER PT J AU Auffray, C Caulfield, T Khoury, MJ Lupski, JR Schwab, M Veenstra, T AF Auffray, Charles Caulfield, Timothy Khoury, Muin J. Lupski, James R. Schwab, Matthias Veenstra, Timothy TI Looking back at genomic medicine in 2011 SO GENOME MEDICINE LA English DT Editorial Material ID REARRANGEMENTS; HLA-A-ASTERISK-3101; POPULATION; MICROBIOME; DISEASE C1 [Auffray, Charles] Univ Lyon 1, European Inst Syst Biol & Med, CNRS Inst Biol Sci, F-69007 Lyon, France. [Caulfield, Timothy] Univ Alberta, Fac Law, Edmonton, AB T6G 2H5, Canada. [Caulfield, Timothy] Univ Alberta, Law Ctr 461, Sch Publ Hlth, Edmonton, AB T6G 2H5, Canada. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA. [Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA. [Schwab, Matthias] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70367 Stuttgart, Germany. [Schwab, Matthias] Univ Tubingen Hosp, Inst Expt & Clin Pharmacol & Toxicol, Dept Clin Pharmacol, D-72076 Tubingen, Germany. [Veenstra, Timothy] NCI, Lab Prote & Analyt Technol, Frederick, MD 21702 USA. RP Auffray, C (reprint author), Univ Lyon 1, European Inst Syst Biol & Med, CNRS Inst Biol Sci, F-69007 Lyon, France. EM auffray@vjf.cnrs.fr FU NCRR NIH HHS [M01 RR000188]; NINDS NIH HHS [R01 NS058529] NR 37 TC 5 Z9 5 U1 1 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PD JAN 30 PY 2012 VL 4 AR 9 DI 10.1186/gm308 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 084UQ UT WOS:000314565000001 PM 22293121 ER PT J AU French, M Kinter, A AF French, Martyn Kinter, Audrey TI Regulatory T cells are converts in simian immunodeficiency virus infection SO AIDS LA English DT Editorial Material DE dendritic cells; lymphoid tissue; simian immunodeficiency virus ID DENDRITIC CELLS; IMMUNE ACTIVATION; HIV-INFECTION; INDOLEAMINE 2,3-DIOXYGENASE; RHESUS MACAQUES; INDUCTION; MECHANISM; MUCOSAL; GUT C1 [Kinter, Audrey] NIAID, LMM, NIH, Bethesda, MD 20982 USA. [French, Martyn] Univ Western Australia, Royal Perth Hosp, Perth CBD Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia. RP Kinter, A (reprint author), NIAID, LMM, NIH, Bldg 4,Rm 341,9000 Rockville Pike, Bethesda, MD 20982 USA. EM akinter@niaid.nih.gov NR 20 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 28 PY 2012 VL 26 IS 3 BP 395 EP 396 DI 10.1097/QAD.0b013e32834ee778 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 876NV UT WOS:000299115300016 PM 22217503 ER PT J AU Yan, CG Zhu, M Staiger, J Johnson, PF Gao, HW AF Yan, Chunguang Zhu, Mei Staiger, Jennifer Johnson, Peter F. Gao, Hongwei TI C5a-regulated CCAAT/Enhancer-binding Proteins beta and delta Are Essential in Fc gamma Receptor-mediated Inflammatory Cytokine and Chemokine Production in Macrophages SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C/EBP-BETA; PROINFLAMMATORY CYTOKINES; KINASE ACTIVATION; IMMUNE-COMPLEXES; LUNG INJURY; GENE; EXPRESSION; INDUCTION; CELLS; C5A AB CCAAT/enhancer-binding protein beta (C/EBP beta) and C/EBP delta are known to participate in the regulation of many genes associated with inflammation. However, little is known about the activation and function of C/EBP beta and -delta in inflammatory responses elicited by Fc gamma receptor (Fc gamma R) activation. Here we show that C/EBP beta and -delta activation are induced in IgG immune complex (IC)-treated macrophages. The increased expression of C/EBP beta and -delta occurred at both mRNA and protein levels. Furthermore, induction of C/EBP beta and -delta was mediated, to a large extent, by activating Fc gamma Rs. Using siRNA-mediated knockdown as well as macrophages deficient for C/EBP beta and/or -delta, we demonstrate that C/EBP beta and -delta play a critical role in the production of TNF-alpha, MIP-2, and MIP-1 alpha in IgG IC-stimulated macrophages. Moreover, both ERK1/2 and p38 MAPK are involved in C/EBP induction and TNF-alpha, MIP-2, and MIP-1 alpha production induced by IgGIC. We provide the evidence that C5a regulates IgGIC-induced inflammatory responses by enhancing ERK1/2 and p38 MAPK activities as well as C/EBP beta and -delta activities. Collectively, these data suggest that C/EBP beta and -delta are key regulators for Fc gamma R-mediated induction of cytokines and chemokines in macrophages. Furthermore, C/EBPs may play an important regulatory role in IC-associated inflammatory responses. C1 [Yan, Chunguang; Gao, Hongwei] Harvard Univ, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med,Sch Med, Boston, MA 02115 USA. [Zhu, Mei] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Staiger, Jennifer] Mt St Marys Univ, Dept Sci, Sch Nat Sci & Math, Emmitsburg, MD 21727 USA. [Johnson, Peter F.] NCI, Lab Canc Prevent, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Gao, HW (reprint author), Harvard Univ, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol,Sch Med, 20 Shattuck St, Boston, MA 02115 USA. EM hgao@zeus.bwh.harvard.edu FU National Institutes of Health (NIH) [5R01HL092905-04, 3R01HL092905-02S1]; NIH, NCI, Center for Cancer Research FX This work was supported, in whole or in part, by National Institutes of Health (NIH) Grants 5R01HL092905-04 and 3R01HL092905-02S1 (to H. G.) and the Intramural Research Program of the NIH, NCI, Center for Cancer Research. NR 53 TC 18 Z9 19 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 27 PY 2012 VL 287 IS 5 BP 3217 EP 3230 DI 10.1074/jbc.M111.280834 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 892OI UT WOS:000300295100027 PM 22147692 ER PT J AU Mburu, YK Egloff, AM Walker, WH Wang, L Seethala, RR van Waes, C Ferris, RL AF Mburu, Yvonne K. Egloff, Ann Marie Walker, William H. Wang, Lin Seethala, Raja R. van Waes, Carter Ferris, Robert L. TI Chemokine Receptor 7 (CCR7) Gene Expression Is Regulated by NF-kappa B and Activator Protein 1 (AP1) in Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CANCER; PROLIFERATION; TRANSCRIPTION; PATHWAYS; APOPTOSIS; CYTOKINES; BIOLOGY; LINES; IL-8; AP-1 AB The chemokine receptor CCR7 is a seven-transmembrane domain G-protein-coupled receptor that facilitates leukocyte migration to regional lymph nodes. Aberrant CCR7 expression in a number of human malignancies has been linked to prosurvival, -invasive, and -metastatic pathways. We demonstrate here that up-regulation of CCR7 in squamous cell carcinoma of the head and neck (SCCHN) patient tumors correlates with lower survival because of metastatic disease. Because of this important oncogenic phenotype, we investigated the mechanisms that regulate CCR7 expression in these tumors. Interestingly, the inflammatory transcription factor NF-kappa B has been associated with a more aggressive SCCHN phenotype. Immunohistochemical staining of a SCCHN tumor cohort (n = 47) strongly linked NF-kappa B staining and CCR7 expression in SCCHN. Thus, we investigated whether NF-kappa B contributes to metastatic disease by promoting CCR7 expression in SCCHN tumor cells. Wecharacterized four novel, potential NF-kappa B binding sites in the 1000-bp promoter region upstream of the CCR7 gene, using luciferase, ChIP, and EMSA. However, NF-kappa B inhibition only resulted in partial reduction in CCR7 expression, prompting consideration of other co-regulators of CCR7. Indeed, cooperation between NF-kappa B and AP1 transcription factors, which are often co-activated, is crucial to the regulation of CCR7 mRNA expression in metastatic SCCHN cells. Thus, our findings support an important biological role for inflammatory NF-kappa B and AP1 in the regulation of CCR7 expression in metastatic SCCHN. As such, CCR7, NF-kappa B, and AP1 could be potentially useful therapeutic targets in controlling the progression and metastasis of SCCHN tumors. C1 [Ferris, Robert L.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA. [Mburu, Yvonne K.; Ferris, Robert L.] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15261 USA. [Egloff, Ann Marie; Ferris, Robert L.] Univ Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Walker, William H.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Wang, Lin; Seethala, Raja R.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA. [van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Bethesda, MD 20892 USA. RP Ferris, RL (reprint author), Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Res Wing,Rm 2-26B,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM ferrisrl@upmc.edu FU National Institutes of Health [1R01 CA115902] FX This work was supported, in whole or in part, by National Institutes of Health Grant 1R01 CA115902 (to R. L. F.). NR 28 TC 21 Z9 22 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 27 PY 2012 VL 287 IS 5 BP 3581 EP 3590 DI 10.1074/jbc.M111.294876 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 892OI UT WOS:000300295100062 PM 22158872 ER PT J AU Chen, WZ Streaker, ED Russ, DE Feng, Y Prabakaran, P Dimitrov, DS AF Chen, Weizao Streaker, Emily D. Russ, Daniel E. Feng, Yang Prabakaran, Ponraj Dimitrov, Dimiter S. TI Characterization of germline antibody libraries from human umbilical cord blood and selection of monoclonal antibodies to viral envelope glycoproteins: Implications for mechanisms of immune evasion and design of vaccine immunogens SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE HIV-1; Human monoclonal antibody; IgM; gp120; Envelope glycoprotein; Immunogen ID NEUTRALIZING ANTIBODIES; HIV-1 GP120; CONSTRUCTION; VIRUS; EXPRESSION; BINDING; HENDRA; DOMAIN AB We have previously observed that all known HIV-1 broadly neutralizing antibodies (bnAbs) are highly divergent from germline antibodies in contrast to bnAbs against Hendra virus, Nipah virus and SARS coronavirus (SARS CoV). We have hypothesized that because the germline antibodies are so different from the mature HIV-1-specific bnAbs they may not bind the epitopes of the mature antibodies and provided the first evidence to support this hypothesis by using individual putative germline-like predecessor antibodies. To further validate the hypothesis and understand initial immune responses to different viruses, two phage-displayed human cord blood-derived IgM libraries were constructed which contained mostly germline antibodies or antibodies with very low level of somatic hypermutations. They were panned against different HIV-1 envelope glycoproteins (Envs), SARS Coy protein receptor-binding domain (RBD), and soluble Hendra virus G protein (sG). Despite a high sequence and combinatorial diversity observed in the cord blood-derived IgM antibody repertoire, no enrichment for binders of Envs was observed in contrast to considerable specific enrichments produced with panning against RBD and sG; one of the selected monoclonal antibodies (against the RBD) was of high (nM) affinity with only few somatic mutations. These results further support and expand our initial hypothesis for fundamental differences in immune responses leading to elicitation of bnAbs against HIV-1 compared to SARS CoV and Hendra virus. HIV-1 uses a strategy to minimize or eliminate strong binding of germline antibodies to its Env; in contrast, SARS CoV and Hendra virus, and perhaps other viruses causing acute infections, can bind germline antibody or minimally somatically mutated antibodies with relatively high affinity which could be one of the reasons for the success of sG and RBD as vaccine immunogens. Published by Elsevier Inc. C1 [Chen, Weizao; Streaker, Emily D.; Feng, Yang; Prabakaran, Ponraj; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA. [Streaker, Emily D.; Prabakaran, Ponraj] NCI, Basic Res Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. [Russ, Daniel E.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Bldg 469,Rm 150B, Frederick, MD 21702 USA. EM dimiter.dimitrov@nih.gov OI Russ, Daniel/0000-0003-4040-4416 FU NIH, National Cancer Institute, Center for Cancer Research; Gates Foundation; NIH, National Cancer Institute [NO1-CO-12400] FX We thank Drs. C. Broder, B. Haynes, H. Liao and T. Fouts for reagents. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and the Gates Foundation to DSD, and by Federal funds from the NIH, National Cancer Institute, under Contract No. NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 23 TC 16 Z9 17 U1 0 U2 4 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 1164 EP 1169 DI 10.1016/j.bbrc.2011.12.089 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 891DG UT WOS:000300196100010 PM 22226962 ER PT J AU Bera, TK Walker, DA Sherins, RJ Pastan, I AF Bera, Tapan K. Walker, Dawn A. Sherins, Richard J. Pastan, Ira TI POTE protein, a cancer-testis antigen, is highly expressed in spermatids in human testis and is associated with apoptotic cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE POTE gene family; Spermatids; Apoptosis; Cleaved Caspase-3 ID SPERMATOGENESIS; ANTIBODIES; PARALOGS; PROSTATE AB The POTE gene family encodes very closely related proteins that are highly expressed in testis and in many cancers. Recent studies indicate that the POTE proteins have a pro-apoptotic function. To examine if POTE is associated with cells that are undergoing apoptosis in testis, we determined the cellular location of POTE and of Cleaved Caspase-3 in testicular tissues from 26 azoospermic men. We found intense expression of POTE in round spermatids that are undergoing apoptosis, which are positive for Cleaved Caspase-3. This study suggests POTE may have a role in apoptosis in the human testis. Published by Elsevier Inc. C1 [Bera, Tapan K.; Walker, Dawn A.; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sherins, Richard J.] NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM BeraT@mail.nih.gov; walkerd@mail.nih.gov; rsherins@comcast.net; pastani@mail.nih.gov FU NIH, National Cancer Institute; National Institute of Child Health and Human Development, National Institutes of Health FX T.K.B., D.A.W., and I.P.'s research was supported by the Intramural Research Program of the NIH, National Cancer Institute; R.J.S.'s research was supported by the National Institute of Child Health and Human Development, National Institutes of Health. NR 12 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 27 PY 2012 VL 417 IS 4 BP 1271 EP 1274 DI 10.1016/j.bbrc.2011.12.125 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 891DG UT WOS:000300196100028 PM 22234308 ER PT J AU Pearce, MS Salotti, JA McHugh, K Kim, KP Craft, AW Lubin, J Ron, E Parker, L AF Pearce, Mark S. Salotti, Jane A. McHugh, Kieran Kim, Kwang Pyo Craft, Alan W. Lubin, Jay Ron, Elaine Parker, Louise TI Socio-economic variation in CT scanning in Northern England, 1990-2002 SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID RADIATION-EXPOSURE; PEDIATRIC CT; CANCER-RISKS; INJURIES; CHILDREN; UK; PATTERNS; SCANS AB Background: Socio-economic status is known to influence health throughout life. In childhood, studies have shown increased injury rates in more deprived settings. Socio-economic status may therefore be related to rates of certain medical procedures, such as computed tomography (CT) scans. This study aimed to assess socio-economic variation among young people having CT scans in Northern England between 1990 and 2002 inclusive. Methods: Electronic data were obtained from Radiology Information Systems of all nine National Health Service hospital Trusts in the region. CT scan data, including sex, date of scan, age at scan, number and type of scans were assessed in relation to quintiles of Townsend deprivation scores, obtained from linkage of postcodes with census data, using chi(2) tests and Spearman rank correlations. Results: During the study period, 39,676 scans were recorded on 21,089 patients, with 38,007 scans and 19,485 patients (11344 male and 8132 female) linkable to Townsend scores. The overall distributions of both scans and patients by quintile of Townsend deprivation scores were significantly different to the distributions of Townsend scores from the census wards included in the study (p < 0.0001). There was a significant association between type of scan and deprivation quintile (p < 0.0001), primarily due to the higher proportions of head scans in the three most deprived quintiles, and slightly higher proportions of chest scans and abdomen and pelvis scans in the least deprived groups. There was also a significant association (p < 0.0001) between the patient's age at the time of the CT scan and Townsend deprivation quintiles, with slightly increasing proportions of younger children with increasing deprivation. A similar association with age (p < 0.0001) was seen when restricting the data to include only the first scan of each patient. The number of scans per patient was also associated with Townsend deprivation quintiles (p = 0.014). Conclusions: Social inequalities exist in the numbers of young people undergoing CT scans with those from deprived areas more likely to do so. This may reflect the rates of injuries in these individuals and implies that certain groups within the population may receive higher radiation doses than others due to medical procedures. C1 [Pearce, Mark S.; Salotti, Jane A.] Newcastle Univ, Royal Victoria Infirm, Sir James Spence Inst, Inst Hlth & Soc, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [McHugh, Kieran] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Kim, Kwang Pyo] Kyung Hee Univ, Dept Nucl Engn, Gyeonggi Do, South Korea. [Craft, Alan W.] Newcastle Univ, Royal Victoria Infirm, Sir James Spence Inst, No Inst Canc Res, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Lubin, Jay] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Parker, Louise] Dalhousie Univ, Dept Med & Paediat, Populat Canc Res Program, Halifax, NS, Canada. [Parker, Louise] Canc Care Nova Scotia, Halifax, NS, Canada. RP Pearce, MS (reprint author), Newcastle Univ, Royal Victoria Infirm, Sir James Spence Inst, Inst Hlth & Soc, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. EM mark.pearce@ncl.ac.uk FU US National Cancer Institute [NO2-CP-75501]; UK Department of Health [RRX 119] FX This study was supported by contract NO2-CP-75501 from the US National Cancer Institute and through the Radiation Research Programme of the UK Department of Health (RRX 119). We thank the staff in radiology departments across the Northern England who contributed data and to Katharine Kirton, Wenhua Metcalf and Richard Hardy for their assistance. NR 22 TC 8 Z9 8 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD JAN 27 PY 2012 VL 12 AR 24 DI 10.1186/1472-6963-12-24 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 889GH UT WOS:000300061100001 PM 22283843 ER PT J AU Wang, XH Zhang, YB Yang, XXO Nurieva, RI Chang, SH Ojeda, SS Kang, HS Schluns, KS Gui, JF Jetten, AM Dong, C AF Wang, Xiaohu Zhang, Yibing Yang, Xuexian O. Nurieva, Roza I. Chang, Seon Hee Ojeda, Sandra S. Kang, Hong S. Schluns, Kimberly S. Gui, Jianfang Jetten, Anton M. Dong, Chen TI Transcription of Il17 and Il17f Is Controlled by Conserved Noncoding Sequence 2 SO IMMUNITY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RANGE INTRACHROMOSOMAL INTERACTIONS; CD4(+) T-CELLS; ROR-GAMMA-T; NUCLEAR RECEPTORS; GENE-EXPRESSION; DIFFERENTIATION; CYTOKINE; LOCUS; LINEAGE AB T helper 17 (Th17) cells specifically transcribe the Il17 and Il17f genes, which are localized in the same chromosome region, but the underlying mechanism is unclear. Here, we report a cis element that we previously named conserved noncoding sequence 2 (CNS2) physically interacted with both Il17 and Il17f gene promoters and was sufficient for regulating their selective transcription in Th17 cells. Targeted deletion of CNS2 resulted in impaired retinoic acid-related orphan receptor gammat (ROR gamma t)-driven IL-17 expression in vitro. CNS2-deficient T cells also produced substantially decreased amounts of IL-17F. These cytokine defects were associated with defective chromatin remodeling in the Ild17-Il17f gene locus, possibly because of effects on CNS2-mediated recruitment of histone-modifying enzymes p300 and JmjC domain-containing protein 3 (JMJD3). CNS2-deficient animals were also shown to be resistant to experimental autoimmune encephalomyelitis (EAE). Our results thus suggest that CNS2 is sufficient and necessary for Il17 and optimal Il17f gene transcription in Th17 cells. C1 [Wang, Xiaohu; Zhang, Yibing; Yang, Xuexian O.; Nurieva, Roza I.; Chang, Seon Hee; Ojeda, Sandra S.; Schluns, Kimberly S.; Dong, Chen] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. [Zhang, Yibing; Gui, Jianfang] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China. [Kang, Hong S.; Jetten, Anton M.] NIEHS, Cell Biol Sect, LRB, NIH, Res Triangle Pk, NC 27709 USA. RP Dong, C (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. EM cdong@mdanderson.org RI dong, chen /B-3181-2009; OI dong, chen /0000-0002-0084-9130; Jetten, Anton/0000-0003-0954-4445 FU NIH; American Heart Association; 973 National Basic Research Program of China [2010CB126301]; National Multiple Sclerosis Society; Chinese Academy of Sciences; MD Anderson Cancer Center; Leukemia and Lymphoma Society FX We thank the C.D. laboratory members for their help. The work is supported by research grants from NIH (to C.D. and R.I.N.), American Heart Association (to X.O.Y.), and 973 National Basic Research Program of China (2010CB126301). X.W. receives a postdoctoral fellowship from the National Multiple Sclerosis Society, Y.Z. was supported by a fellowship from Chinese Academy of Sciences, and C.D. receives a Research Trust Fellowship from MD Anderson Cancer Center and is a Leukemia and Lymphoma Society Scholar. C.D. and X.W. designed the research and analyzed the data. X.W., Y.Z., X.O.Y., RN., S.H.C., S.S.O., and H.S.K. performed the experiments, and X.W., J.G., K.S.S., A.M.J., and C.D. prepared the manuscript. NR 37 TC 37 Z9 42 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN 27 PY 2012 VL 36 IS 1 BP 23 EP 31 DI 10.1016/j.immuni.2011.10.019 PG 9 WC Immunology SC Immunology GA 885GG UT WOS:000299766000007 PM 22244845 ER PT J AU Tikhonova, AN Van Laethem, F Hanada, K Lu, JH Pobezinsky, LA Hong, CW Guinter, TI Jeurling, SK Bernhardt, G Park, JH Yang, JC Sun, PD Singer, A AF Tikhonova, Anastasia N. Van Laethem, Francois Hanada, Ken-ichi Lu, Jinghua Pobezinsky, Leonid A. Hong, Changwan Guinter, Terry I. Jeurling, Susanna K. Bernhardt, Guenter Park, Jung-Hyun Yang, James C. Sun, Peter D. Singer, Alfred TI alpha beta T Cell Receptors that Do Not Undergo Major Histocompatibility Complex-Specific Thymic Selection Possess Antibody-like Recognition Specificities SO IMMUNITY LA English DT Article ID NECTIN-LIKE MOLECULES; CLASS-I; IMMUNOGLOBULIN SUPERFAMILY; CRYSTAL-STRUCTURE; MHC INTERACTION; AMINO-ACIDS; PEPTIDE; ANTIGEN; BINDING; CD4 AB Major histocompatibility complex (MHC) restriction is the cardinal feature of T cell antigen recognition and is thought to be intrinsic to alpha beta T cell receptor (TCR) structure because of germline-encoded residues that impose MHC specificity. Here, we analyzed alpha beta TCRs from T cells that had not undergone MHC-specific thymic selection. Instead of recognizing peptide-MHC complexes, the two alpha beta TCRs studied here resembled antibodies in recognizing glycosylation-dependent conformational epitopes on a native self-protein, CD155, and they did so with high affinity independently of MHC molecules. Ligand recognition was via the alpha beta TCR combining site and involved the identical germline-encoded residues that have been thought to uniquely impose MHC specificity, demonstrating that these residues do not only promote MHC binding. This study demonstrates that, without MHC-specific thymic selection, alpha beta TCRs can resemble antibodies in recognizing conformational epitopes on MHC-independent ligands. C1 [Tikhonova, Anastasia N.; Van Laethem, Francois; Pobezinsky, Leonid A.; Hong, Changwan; Guinter, Terry I.; Jeurling, Susanna K.; Park, Jung-Hyun; Singer, Alfred] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Hanada, Ken-ichi; Yang, James C.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Tikhonova, Anastasia N.] Univ Penn, Sch Med, Immunol Grad Grp, Philadelphia, PA 19104 USA. [Lu, Jinghua; Sun, Peter D.] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Bernhardt, Guenter] Hannover Med Sch, Inst Immunol, D-30625 Hannover, Germany. RP Singer, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM singera@nih.gov RI lu, jinghua/G-5872-2012; Hanada, Ken-ichi/L-2481-2013; Bernhardt, Gunter/F-6946-2012; Tikhonova, Anastasia/F-1186-2015; Park, Jung Hyun /B-5712-2015 OI Hanada, Ken-ichi/0000-0003-2959-1257; Park, Jung Hyun /0000-0002-9547-9055 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank R. Bosselut, W. Pear, and A. Chervonsky for providing reagents and N. Taylor, J. Di Santo, M. Kimura, T. McCaughtry, X. Tai, and D. Margulies for critically reading the manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 37 TC 51 Z9 51 U1 0 U2 5 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 79 EP 91 DI 10.1016/j.immuni.2011.11.013 PG 13 WC Immunology SC Immunology GA 885GG UT WOS:000299766000012 PM 22209676 ER EF