FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sequist, LV Gettinger, S Natale, R Martins, R Lilenbaum, R Janne, P Gray, J Samuel, TA Grayzel, D Lynch, TJ AF Sequist, L. V. Gettinger, S. Natale, R. Martins, R. Lilenbaum, R. Jaenne, P. Gray, J. Samuel, T. A. Grayzel, D. Lynch, T. J. TI A phase II trial of IPI-504 (retaspimycin hydrochloride), a novel Hsp90 inhibitor, in patients with relapsed and/or refractory stage IIIb or stage IV non-small cell lung cancer (NSCLC) stratified by EGFR mutation status SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Sequist, L. V.; Gettinger, S.; Natale, R.; Martins, R.; Lilenbaum, R.; Jaenne, P.; Gray, J.; Samuel, T. A.; Grayzel, D.; Lynch, T. J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Sequist, L. V.; Gettinger, S.; Natale, R.; Martins, R.; Lilenbaum, R.; Jaenne, P.; Gray, J.; Samuel, T. A.; Grayzel, D.; Lynch, T. J.] Yale Comprehens Canc Ctr, New Haven, CT USA. [Sequist, L. V.; Gettinger, S.; Natale, R.; Martins, R.; Lilenbaum, R.; Jaenne, P.; Gray, J.; Samuel, T. A.; Grayzel, D.; Lynch, T. J.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Sequist, L. V.; Gettinger, S.; Natale, R.; Martins, R.; Lilenbaum, R.; Jaenne, P.; Gray, J.; Samuel, T. A.; Grayzel, D.; Lynch, T. J.] Seattle Canc Care Alliance, Seattle, WA USA. [Sequist, L. V.; Gettinger, S.; Natale, R.; Martins, R.; Lilenbaum, R.; Jaenne, P.; Gray, J.; Samuel, T. A.; Grayzel, D.; Lynch, T. J.] Mt Sinai Comprehens Canc Ctr, Miami Beach, FL USA. [Sequist, L. V.; Gettinger, S.; Natale, R.; Martins, R.; Lilenbaum, R.; Jaenne, P.; Gray, J.; Samuel, T. A.; Grayzel, D.; Lynch, T. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sequist, L. V.; Gettinger, S.; Natale, R.; Martins, R.; Lilenbaum, R.; Jaenne, P.; Gray, J.; Samuel, T. A.; Grayzel, D.; Lynch, T. J.] Infinity Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 8073 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606605275 ER PT J AU Sessa, C Sharma, SK Britten, CD Vogelzang, NJ Bhalla, KN Mita, MM Pluard, TJ Stiegler, P Quadt, C Shapiro, GI AF Sessa, C. Sharma, S. K. Britten, C. D. Vogelzang, N. J. Bhalla, K. N. Mita, M. M. Pluard, T. J. Stiegler, P. Quadt, C. Shapiro, G. I. TI A phase I dose escalation study of AUY922, a novel HSP90 inhibitor, in patients with advanced solid malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 IOSI, Bellinzona, Switzerland. Nevada Canc Inst, Las Vegas, NV USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Med Coll Georgia, Augusta, GA 30912 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Washington Univ, Sch Med, St Louis, MO USA. Novartis Pharmaceut, Florham Pk, NJ USA. Novartis Pharmaceut, Basel, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 3532 PG 3 WC Oncology SC Oncology GA 582OF UT WOS:000276606602422 PM 27961345 ER PT J AU Shapiro, G Kwak, E Baselga, J Rodon, J Scheffold, C Laird, AD Bedell, C Edelman, G AF Shapiro, G. Kwak, E. Baselga, J. Rodon, J. Scheffold, C. Laird, A. D. Bedell, C. Edelman, G. TI Phase I dose-escalation study of XL147, a PI3K inhibitor administered orally to patients with solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Shapiro, G.; Kwak, E.; Baselga, J.; Rodon, J.; Scheffold, C.; Laird, A. D.; Bedell, C.; Edelman, G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shapiro, G.; Kwak, E.; Baselga, J.; Rodon, J.; Scheffold, C.; Laird, A. D.; Bedell, C.; Edelman, G.] Vall DHebron Univ Hosp, Barcelona, Spain. [Shapiro, G.; Kwak, E.; Baselga, J.; Rodon, J.; Scheffold, C.; Laird, A. D.; Bedell, C.; Edelman, G.] Exelixis Inc, San Francisco, CA USA. [Shapiro, G.; Kwak, E.; Baselga, J.; Rodon, J.; Scheffold, C.; Laird, A. D.; Bedell, C.; Edelman, G.] Texas Oncol, Irving, TX USA. NR 0 TC 11 Z9 12 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 3500 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606602390 PM 27961287 ER PT J AU Siegel, DS Weber, DM Mitsiades, CS Dimopoulos, MA Harousseau, JL Rizvi, S Howe, J Reiser, D Anderson, KC Richardson, PG AF Siegel, D. S. Weber, D. M. Mitsiades, C. S. Dimopoulos, M. A. Harousseau, J. L. Rizvi, S. Howe, J. Reiser, D. Anderson, K. C. Richardson, P. G. TI Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma: A phase I study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Siegel, D. S.; Weber, D. M.; Mitsiades, C. S.; Dimopoulos, M. A.; Harousseau, J. L.; Rizvi, S.; Howe, J.; Reiser, D.; Anderson, K. C.; Richardson, P. G.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Siegel, D. S.; Weber, D. M.; Mitsiades, C. S.; Dimopoulos, M. A.; Harousseau, J. L.; Rizvi, S.; Howe, J.; Reiser, D.; Anderson, K. C.; Richardson, P. G.] MD Anderson Canc Ctr, Houston, TX USA. [Siegel, D. S.; Weber, D. M.; Mitsiades, C. S.; Dimopoulos, M. A.; Harousseau, J. L.; Rizvi, S.; Howe, J.; Reiser, D.; Anderson, K. C.; Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Siegel, D. S.; Weber, D. M.; Mitsiades, C. S.; Dimopoulos, M. A.; Harousseau, J. L.; Rizvi, S.; Howe, J.; Reiser, D.; Anderson, K. C.; Richardson, P. G.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Siegel, D. S.; Weber, D. M.; Mitsiades, C. S.; Dimopoulos, M. A.; Harousseau, J. L.; Rizvi, S.; Howe, J.; Reiser, D.; Anderson, K. C.; Richardson, P. G.] Ctr Rene Gauducheau, Saint Herblain, France. [Siegel, D. S.; Weber, D. M.; Mitsiades, C. S.; Dimopoulos, M. A.; Harousseau, J. L.; Rizvi, S.; Howe, J.; Reiser, D.; Anderson, K. C.; Richardson, P. G.] Merck & Co Inc, Upper Gwynedd, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 8586 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606605495 PM 27962293 ER PT J AU Skarin, AT Vekeman, F Laliberte, F Afonja, O Lafeuille, M Barghout, V Duh, MS AF Skarin, A. T. Vekeman, F. Laliberte, F. Afonja, O. Lafeuille, M. Barghout, V. Duh, M. S. TI Pattern of utilization of pegfilgrastim in patients with chemotherapy-induced neutropenia: A retrospective analysis of administrative claims data SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Grp Analyse Ltee, Montreal, PQ, Canada. Bayer HealthCare Pharmaceut, Wayne, NJ USA. Anal Grp Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 9624 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606606242 PM 27963900 ER PT J AU Small, E Harzstark, A Weinberg, VK Smith, DC Mathew, P Beer, T Liu, G Sharib, J Rosenberg, J AF Small, E. Harzstark, A. Weinberg, V. K. Smith, D. C. Mathew, P. Beer, T. Liu, G. Sharib, J. Rosenberg, J. TI Ixabepilone, mitoxantrone, and prednisone in patients with metastatic castration-resistant prostate cancer refractory to docetaxel-based therapy: A phase II study of the DOD Prostate Cancer Clinical Trials Consortium SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Michigan, Ann Arbor, MI 48109 USA. MD Anderson Canc Ctr, Houston, TX USA. OHSU, Portland, OR USA. Univ Wisconsin, Madison, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 5058 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606603458 ER PT J AU Smith, MR Ellis, G Saad, F Tammela, T Bone, H Egerdie, B Ke, C Jun, S Dansey, R Goessl, C AF Smith, M. R. Ellis, G. Saad, F. Tammela, T. Bone, H. Egerdie, B. Ke, C. Jun, S. Dansey, R. Goessl, C. TI Effect of denosumab on bone mineral density (BMD) in women with breast cancer (BC) and men with prostate cancer (PC) undergoing hormone ablation therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Seattle Canc Care Alliance, Seattle, WA USA. Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. Tampere Univ Hosp, Tampere, Finland. Michigan Bone & Mineral Clin, Detroit, MI USA. Urol Associates Urol Med Res, Kitchener, ON, Canada. Amgen Inc, Thousand Oaks, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 9520 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606606139 PM 27964507 ER PT J AU Snyder, CF Frick, KD Blackford, AL Herbert, RJ Neville, BA Carducci, MA Earle, CC AF Snyder, C. F. Frick, K. D. Blackford, A. L. Herbert, R. J. Neville, B. A. Carducci, M. A. Earle, C. C. TI Costs of treatments for local/regional prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Clin Evaluat Sci, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 6527 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606604376 PM 27964033 ER PT J AU Sorensen, AG Jenning, D Wang, M Andronesi, O Chen, P Prados, M Wen, P Jackson, E Cha, S deGroot, J AF Sorensen, A. G. Jenning, D. Wang, M. Andronesi, O. Chen, P. Prados, M. Wen, P. Jackson, E. Cha, S. deGroot, J. TI Use of neurovascular imaging in GBM patients (pts) to quantify early physiologic changes after treatment with XL184, an inhibitor of multiple receptor tyrosine kinases: Results from a phase II study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Sorensen, A. G.; Jenning, D.; Wang, M.; Andronesi, O.; Chen, P.; Prados, M.; Wen, P.; Jackson, E.; Cha, S.; deGroot, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sorensen, A. G.; Jenning, D.; Wang, M.; Andronesi, O.; Chen, P.; Prados, M.; Wen, P.; Jackson, E.; Cha, S.; deGroot, J.] UCSF, San Francisco, CA USA. [Sorensen, A. G.; Jenning, D.; Wang, M.; Andronesi, O.; Chen, P.; Prados, M.; Wen, P.; Jackson, E.; Cha, S.; deGroot, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sorensen, A. G.; Jenning, D.; Wang, M.; Andronesi, O.; Chen, P.; Prados, M.; Wen, P.; Jackson, E.; Cha, S.; deGroot, J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 2048 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606602196 PM 27964638 ER PT J AU Srinivasan, R Linehan, WM Vaishampayan, U Logan, T Shankar, SM Sherman, LJ Liu, Y Choueiri, TK AF Srinivasan, R. Linehan, W. M. Vaishampayan, U. Logan, T. Shankar, S. M. Sherman, L. J. Liu, Y. Choueiri, T. K. TI A phase II study of two dosing regimens of GSK 1363089 (GSK089), a dual MET/VEGFR2 inhibitor, in patients (pts) with papillary renal carcinoma (PRC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. GlaxoSmithKline Inc, Collegeville, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 5103 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606603502 ER PT J AU Stone, RM Kim, DW Kantarjian, HM Rousselot, P Hochhaus, A Dorlhiac-Llacer, PE Milone, J Matloub, Y Lambert, A Shah, NP AF Stone, R. M. Kim, D. W. Kantarjian, H. M. Rousselot, P. Hochhaus, A. Dorlhiac-Llacer, P. E. Milone, J. Matloub, Y. Lambert, A. Shah, N. P. TI Dasatinib dose-optimization study in chronic phase chronic myeloid leukemia (CML-CP): Three-year follow-up with dasatinib 100 mg once daily and landmark analysis of cytogenetic response and progression-free survival (PFS) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Catholic Univ Korea, St Marys Hosp, Seoul, South Korea. MD Anderson Canc Ctr, Houston, TX USA. Univ Versailles, Hop Mignot, Le Chesnay, France. Univ Heidelberg, D-6800 Mannheim, Germany. Univ Sao Paulo, Hosp & Clin, Sao Paulo, Brazil. Inst Trasplante Medula Osea, La Plata, Argentina. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Bristol Myers Squibb Co, Braine Lalleud, Belgium. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 7007 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606604567 PM 27961379 ER PT J AU Sullivan, RJ Hoshida, Y Brunet, J Tahan, S Aldridge, J Kwabi, C Gardiner, E McDermott, D Golub, T Atkins, MB AF Sullivan, R. J. Hoshida, Y. Brunet, J. Tahan, S. Aldridge, J. Kwabi, C. Gardiner, E. McDermott, D. Golub, T. Atkins, M. B. TI A single center experience with high-dose (HD) IL-2 treatment for patients with advanced melanoma and pilot investigation of a novel gene expression signature as a predictor of response SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Broad Inst, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 9003 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606606019 ER PT J AU Supko, JG Grossman, SA Peereboom, DM Chowdhary, S Lesser, GJ Nabors, LB Mikkelsen, T Desideri, S Batchelor, TT AF Supko, J. G. Grossman, S. A. Peereboom, D. M. Chowdhary, S. Lesser, G. J. Nabors, L. B. Mikkelsen, T. Desideri, S. Batchelor, T. T. TI Feasibility and phase I trial of tandutinib in patients with recurrent glioblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Supko, J. G.; Grossman, S. A.; Peereboom, D. M.; Chowdhary, S.; Lesser, G. J.; Nabors, L. B.; Mikkelsen, T.; Desideri, S.; Batchelor, T. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Supko, J. G.; Grossman, S. A.; Peereboom, D. M.; Chowdhary, S.; Lesser, G. J.; Nabors, L. B.; Mikkelsen, T.; Desideri, S.; Batchelor, T. T.] Johns Hopkins Univ, Baltimore, MD USA. [Supko, J. G.; Grossman, S. A.; Peereboom, D. M.; Chowdhary, S.; Lesser, G. J.; Nabors, L. B.; Mikkelsen, T.; Desideri, S.; Batchelor, T. T.] Cleveland Clin, Cleveland, OH 44106 USA. [Supko, J. G.; Grossman, S. A.; Peereboom, D. M.; Chowdhary, S.; Lesser, G. J.; Nabors, L. B.; Mikkelsen, T.; Desideri, S.; Batchelor, T. T.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Supko, J. G.; Grossman, S. A.; Peereboom, D. M.; Chowdhary, S.; Lesser, G. J.; Nabors, L. B.; Mikkelsen, T.; Desideri, S.; Batchelor, T. T.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Supko, J. G.; Grossman, S. A.; Peereboom, D. M.; Chowdhary, S.; Lesser, G. J.; Nabors, L. B.; Mikkelsen, T.; Desideri, S.; Batchelor, T. T.] Univ Alabama, Birmingham, AL USA. [Supko, J. G.; Grossman, S. A.; Peereboom, D. M.; Chowdhary, S.; Lesser, G. J.; Nabors, L. B.; Mikkelsen, T.; Desideri, S.; Batchelor, T. T.] Henry Ford Hosp, Detroit, MI 48202 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 2039 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606602187 PM 27964617 ER PT J AU Tannir, N Wong, Y Kollmannsberger, C Ernstoff, MS Perry, DJ Appleman, LJ Posadas, E Qian, J Ricker, JL Michaelson, DM AF Tannir, N. Wong, Y. Kollmannsberger, C. Ernstoff, M. S. Perry, D. J. Appleman, L. J. Posadas, E. Qian, J. Ricker, J. L. Michaelson, D. M. TI Phase II trial of ABT-869 in advanced renal cell cancer (RCC) after sunitinib failure: Efficacy and safety results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Chicago, Chicago, IL 60637 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 5036 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606603437 PM 27962936 ER PT J AU Tay, K Shapiro, G Disinski, M Chirieac, LR Pittaluga, S Jaffe, ES Janik, JE Wiestner, A Wilson, WH Dunleavy, K AF Tay, K. Shapiro, G. Disinski, M. Chirieac, L. R. Pittaluga, S. Jaffe, E. S. Janik, J. E. Wiestner, A. Wilson, W. H. Dunleavy, K. TI Phase I/II study of a hybrid schedule of flavopiridol in relapsed/refractory mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 8563 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606605472 PM 27961020 ER PT J AU Temel, JS Greer, JA Admane, S Jackson, VA Billings, JA Dahlin, CM Jacobsen, JC Blinderman, CD Lynch, TJ Pirl, WF AF Temel, J. S. Greer, J. A. Admane, S. Jackson, V. A. Billings, J. A. Dahlin, C. M. Jacobsen, J. C. Blinderman, C. D. Lynch, T. J., Jr. Pirl, W. F. TI Illness understanding in patients with advanced lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Temel, J. S.; Greer, J. A.; Admane, S.; Jackson, V. A.; Billings, J. A.; Dahlin, C. M.; Jacobsen, J. C.; Blinderman, C. D.; Lynch, T. J., Jr.; Pirl, W. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 9515 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606606134 PM 27964488 ER PT J AU Tercyak, K Peshkin, B DeMarco, T Schneider, K Valdimarsdottir, H Garber, J Patenaude, A AF Tercyak, K. Peshkin, B. DeMarco, T. Schneider, K. Valdimarsdottir, H. Garber, J. Patenaude, A. TI Parental decisions and outcomes regarding disclosing maternal BRCA1 and 2 test results to children SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Tercyak, K.; Peshkin, B.; DeMarco, T.; Schneider, K.; Valdimarsdottir, H.; Garber, J.; Patenaude, A.] Lombardi Comprehens Canc Ctr, Washington, DC USA. [Tercyak, K.; Peshkin, B.; DeMarco, T.; Schneider, K.; Valdimarsdottir, H.; Garber, J.; Patenaude, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tercyak, K.; Peshkin, B.; DeMarco, T.; Schneider, K.; Valdimarsdottir, H.; Garber, J.; Patenaude, A.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 9582,33 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606606201 PM 27963706 ER PT J AU Trice, ED Nilsson, ME Paulk, E DeSanto-Madeya, S Wright, AA Balboni, TA Steiglitz, H Maciejewski, PK Block, SD Prigerson, HG AF Trice, E. D. Nilsson, M. E. Paulk, E. DeSanto-Madeya, S. Wright, A. A. Balboni, T. A. Steiglitz, H. Maciejewski, P. K. Block, S. D. Prigerson, H. G. TI Predictors of aggressive end-of-life care among Hispanic and white advanced cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Massachusetts, Boston, MA 02125 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 9538 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606606157 PM 27964535 ER PT J AU Veverka, KA Malkowicz, B Smith, M Morton, RA Steiner, MS AF Veverka, K. A. Malkowicz, B. Smith, M. Morton, R. A. Steiner, M. S. TI The effect of toremifene citrate on BMD in men on ADT: A phase III clinical trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 GTx Inc, Memphis, TN USA. Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 5055 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606603455 PM 27962973 ER PT J AU Vickers, MM Choueiri, TK Zama, I Cheng, T North, S Knox, JJ Kollmannsberger, C McDermott, DF Rini, BI Heng, DY AF Vickers, M. M. Choueiri, T. K. Zama, I. Cheng, T. North, S. Knox, J. J. Kollmannsberger, C. McDermott, D. F. Rini, B. I. Heng, D. Y. TI Failure of initial VEGF-targeted therapy in metastatic renal cell carcinoma (mRCC): What next? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Tom Baker Canc Clin, Calgary, AB, Canada. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. BC Canc Agcy, Vancouver, BC, Canada. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 5098 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606603497 ER PT J AU Vinson, J Mathew, P Beer, TM Carducci, MA Oh, W Small, E Wilding, G Higano, C Hussain, M Scher, HI AF Vinson, J. Mathew, P. Beer, T. M. Carducci, M. A. Oh, W. Small, E. Wilding, G. Higano, C. Hussain, M. Scher, H. I. TI Prostate cancer clinical trials consortium: A multicenter mechanism for the rapid design, development, and implementation of early phase clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Vinson, J.; Mathew, P.; Beer, T. M.; Carducci, M. A.; Oh, W.; Small, E.; Wilding, G.; Higano, C.; Hussain, M.; Scher, H. I.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Vinson, J.; Mathew, P.; Beer, T. M.; Carducci, M. A.; Oh, W.; Small, E.; Wilding, G.; Higano, C.; Hussain, M.; Scher, H. I.] MD Anderson Canc Ctr, Houston, TX USA. [Vinson, J.; Mathew, P.; Beer, T. M.; Carducci, M. A.; Oh, W.; Small, E.; Wilding, G.; Higano, C.; Hussain, M.; Scher, H. I.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Vinson, J.; Mathew, P.; Beer, T. M.; Carducci, M. A.; Oh, W.; Small, E.; Wilding, G.; Higano, C.; Hussain, M.; Scher, H. I.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Vinson, J.; Mathew, P.; Beer, T. M.; Carducci, M. A.; Oh, W.; Small, E.; Wilding, G.; Higano, C.; Hussain, M.; Scher, H. I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vinson, J.; Mathew, P.; Beer, T. M.; Carducci, M. A.; Oh, W.; Small, E.; Wilding, G.; Higano, C.; Hussain, M.; Scher, H. I.] UCSF, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Vinson, J.; Mathew, P.; Beer, T. M.; Carducci, M. A.; Oh, W.; Small, E.; Wilding, G.; Higano, C.; Hussain, M.; Scher, H. I.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Vinson, J.; Mathew, P.; Beer, T. M.; Carducci, M. A.; Oh, W.; Small, E.; Wilding, G.; Higano, C.; Hussain, M.; Scher, H. I.] Univ Washington, Seattle, WA 98195 USA. [Vinson, J.; Mathew, P.; Beer, T. M.; Carducci, M. A.; Oh, W.; Small, E.; Wilding, G.; Higano, C.; Hussain, M.; Scher, H. I.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA e16065 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606604105 PM 27963069 ER PT J AU Wagner, AJ Von Hoff, DH LoRusso, PM Tibes, R Mazina, KE Ware, JA Yan, Y Derynck, MK Demetri, GD AF Wagner, A. J. Von Hoff, D. H. LoRusso, P. M. Tibes, R. Mazina, K. E. Ware, J. A. Yan, Y. Derynck, M. K. Demetri, G. D. TI A first-in-human phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Wagner, A. J.; Von Hoff, D. H.; LoRusso, P. M.; Tibes, R.; Mazina, K. E.; Ware, J. A.; Yan, Y.; Derynck, M. K.; Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wagner, A. J.; Von Hoff, D. H.; LoRusso, P. M.; Tibes, R.; Mazina, K. E.; Ware, J. A.; Yan, Y.; Derynck, M. K.; Demetri, G. D.] TGen Clin Res Serv, Scottsdale, AZ USA. [Wagner, A. J.; Von Hoff, D. H.; LoRusso, P. M.; Tibes, R.; Mazina, K. E.; Ware, J. A.; Yan, Y.; Derynck, M. K.; Demetri, G. D.] Karmanos Canc Inst, Detroit, MI USA. [Wagner, A. J.; Von Hoff, D. H.; LoRusso, P. M.; Tibes, R.; Mazina, K. E.; Ware, J. A.; Yan, Y.; Derynck, M. K.; Demetri, G. D.] Genentech Inc, San Francisco, CA 94080 USA. NR 0 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 3501 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606602391 PM 27961289 ER PT J AU Wasif, N Tomlinson, JS Maggard, MA Giuliano, AE Ko, CY AF Wasif, N. Tomlinson, J. S. Maggard, M. A. Giuliano, A. E. Ko, C. Y. TI Polypectomy or surgery for malignant colonic polyps: Do we need to change the NCCN guidelines? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Wasif, N.; Tomlinson, J. S.; Maggard, M. A.; Giuliano, A. E.; Ko, C. Y.] John Wayne Canc Inst, Santa Monica, CA USA. [Wasif, N.; Tomlinson, J. S.; Maggard, M. A.; Giuliano, A. E.; Ko, C. Y.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 4031 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606600271 PM 27961549 ER PT J AU Wen, PY Cloughesy, T Kuhn, J Lamborn, K Abrey, LE Lieberman, F Robins, HI Wright, J Prados, MD Gilbert, M AF Wen, P. Y. Cloughesy, T. Kuhn, J. Lamborn, K. Abrey, L. E. Lieberman, F. Robins, H. I. Wright, J. Prados, M. D. Gilbert, M. TI Phase I/II study of sorafenib and temsirolimus for patients with recurrent glioblastoma (GBM) (NABTC 05-02) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Wen, P. Y.; Cloughesy, T.; Kuhn, J.; Lamborn, K.; Abrey, L. E.; Lieberman, F.; Robins, H. I.; Wright, J.; Prados, M. D.; Gilbert, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wen, P. Y.; Cloughesy, T.; Kuhn, J.; Lamborn, K.; Abrey, L. E.; Lieberman, F.; Robins, H. I.; Wright, J.; Prados, M. D.; Gilbert, M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Wen, P. Y.; Cloughesy, T.; Kuhn, J.; Lamborn, K.; Abrey, L. E.; Lieberman, F.; Robins, H. I.; Wright, J.; Prados, M. D.; Gilbert, M.] UT San Antonio, San Antonio, TX USA. [Wen, P. Y.; Cloughesy, T.; Kuhn, J.; Lamborn, K.; Abrey, L. E.; Lieberman, F.; Robins, H. I.; Wright, J.; Prados, M. D.; Gilbert, M.] UCSF, San Francisco, CA USA. [Wen, P. Y.; Cloughesy, T.; Kuhn, J.; Lamborn, K.; Abrey, L. E.; Lieberman, F.; Robins, H. I.; Wright, J.; Prados, M. D.; Gilbert, M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wen, P. Y.; Cloughesy, T.; Kuhn, J.; Lamborn, K.; Abrey, L. E.; Lieberman, F.; Robins, H. I.; Wright, J.; Prados, M. D.; Gilbert, M.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Wen, P. Y.; Cloughesy, T.; Kuhn, J.; Lamborn, K.; Abrey, L. E.; Lieberman, F.; Robins, H. I.; Wright, J.; Prados, M. D.; Gilbert, M.] Univ Wisconsin, Madison, WI USA. [Wen, P. Y.; Cloughesy, T.; Kuhn, J.; Lamborn, K.; Abrey, L. E.; Lieberman, F.; Robins, H. I.; Wright, J.; Prados, M. D.; Gilbert, M.] NCI, Bethesda, MD 20892 USA. [Wen, P. Y.; Cloughesy, T.; Kuhn, J.; Lamborn, K.; Abrey, L. E.; Lieberman, F.; Robins, H. I.; Wright, J.; Prados, M. D.; Gilbert, M.] MD Anderson Canc Ctr, Houston, TX USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 2006 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606602154 PM 27964559 ER PT J AU Wilson, W O'Connor, OO Roberts, AW Czuczman, M Brown, J Xiong, H Xiong, H Chiu, Y Krivoshik, A Enschede, S Humerickhouse, R AF Wilson, W. O'Connor, O. O. Roberts, A. W. Czuczman, M. Brown, J. Xiong, H. Xiong, H. Chiu, Y. Krivoshik, A. Enschede, S. Humerickhouse, R. TI ABT-263 activity and safety in patients with relapsed or refractory lymphoid malignancies in particular chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Abbott Labs, Abbott Pk, IL 60064 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 8574 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606605483 ER PT J AU Wirth, LJ Fogg, M Wang, F Lorch, J Haddad, RI Posner, MR AF Wirth, L. J. Fogg, M. Wang, F. Lorch, J. Haddad, R. I. Posner, M. R. TI Epstein- Barr virus (EBV)-specific immunotherapy in nasopharygneal carcinoma (NPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 6025 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606604231 PM 27962433 ER PT J AU Wong, DT Zhang, L Farrell, J Zhou, H Elashoff, D Gao, K Paster, B AF Wong, D. T. Zhang, L. Farrell, J. Zhou, H. Elashoff, D. Gao, K. Paster, B. TI Salivary biomarkers for pancreatic cancer detection SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Calif Los Angeles, Los Angeles, CA USA. Forsyth Inst, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 4630 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606603218 PM 27964229 ER PT J AU Wright, AA Mack, JW Trice, ED Balboni, TA Block, SD Prigerson, HG AF Wright, A. A. Mack, J. W. Trice, E. D. Balboni, T. A. Block, S. D. Prigerson, H. G. TI Personalized end-of-life care: Associations between patient preferences and treatment intensity near death SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Wright, A. A.; Mack, J. W.; Trice, E. D.; Balboni, T. A.; Block, S. D.; Prigerson, H. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 6516 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606604365 PM 27964022 ER PT J AU Wright, K Munro, E del Carmen, M Goodman, AK AF Wright, K. Munro, E. del Carmen, M. Goodman, A. K. TI Prognosis and comorbidities in stage III and IV endometrial cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Wright, K.; Munro, E.; del Carmen, M.; Goodman, A. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA e16553 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606600148 PM 27960816 ER PT J AU Wu, E Guo, A Williams, D Guerin, A Yu, AP Latremouille-Viau, D Tsaneva, M Signorovitch, J Griffin, JD Bollu, V AF Wu, E. Guo, A. Williams, D. Guerin, A. Yu, A. P. Latremouille-Viau, D. Tsaneva, M. Signorovitch, J. Griffin, J. D. Bollu, V. TI Adverse events associated with escalating imatinib versus switching to dasatinib in patients with chronic myelegenous leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Anal Grp Inc, Boston, MA USA. Novartis Pharmaceut, E Hanover, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 7092 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606605081 PM 27961261 ER PT J AU Wu, J Muggia, F Henderson, C Feun, L Veldhuizen, PV Gold, P Zheng, H Abbadessa, G Lewis, J Zhu, AX AF Wu, J. Muggia, F. Henderson, C. Feun, L. Veldhuizen, P. V. Gold, P. Zheng, H. Abbadessa, G. Lewis, J. Zhu, A. X. TI Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 NYU, Inst Canc, New York, NY 02114 USA. Piedmont Hosp, Res Inst, Atlanta, GA USA. Univ Miami, Hosp & Clin, Miami, FL USA. Kansas City Vet Adm Med Ctr, Kansas City, MO USA. Swedish Canc Inst Res, Seattle, WA USA. Massachusetts Gen Hosp, Boston, MA USA. Ziopharm Oncol, Boston, MA USA. Ziopharm, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA e15630 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606603346 PM 27962745 ER PT J AU Yoon, HH Powell, M Murphy, K Montgomery, EA Hafez, MJ Liu, G Forastiere, AA Benson, AB Kleinberg, LR Gibson, MK AF Yoon, H. H. Powell, M. Murphy, K. Montgomery, E. A. Hafez, M. J. Liu, G. Forastiere, A. A. Benson, A. B. Kleinberg, L. R. Gibson, M. K. CA ECOG E1201-T1 Study Grp TI Outcome prediction based on single nucleotide polymorphisms (SNPs) in DNA repair paths in patients (pts) with esophageal adenocarcinoma (EAC) treated with preoperative (preop) cisplatin (C)-based chemoradiation (CRT): Results from the Eastern Cooperative Oncology Group (ECOG) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Baltimore, MD USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Northwestern Univ, Chicago, IL 60611 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 4530 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606603120 PM 27962996 ER PT J AU Zaman, K Thurlimann, B Huober, J Schonenberger, A Pagani, O Luthi, J Simcock, M Giobbie-Hurder, A Genton, C Aebi, S AF Zaman, K. Thuerlimann, B. Huober, J. Schoenenberger, A. Pagani, O. Luethi, J. Simcock, M. Giobbie-Hurder, A. Genton, C. Aebi, S. CA SAKK TI Modeling bone mineral density (BMD) evolution in postmenopausal patients treated by letrozole (L), tamoxifen (T), and sequences of T and L (SAKK 21/07) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Zaman, K.; Thuerlimann, B.; Huober, J.; Schoenenberger, A.; Pagani, O.; Luethi, J.; Simcock, M.; Giobbie-Hurder, A.; Genton, C.; Aebi, S.] Univ Vaudois, Ctr Hosp, CEPO, Lausanne, Switzerland. [Zaman, K.; Thuerlimann, B.; Huober, J.; Schoenenberger, A.; Pagani, O.; Luethi, J.; Simcock, M.; Giobbie-Hurder, A.; Genton, C.; Aebi, S.] Kantonspital St Gallen, Breast Ctr, St Gallen, Switzerland. [Zaman, K.; Thuerlimann, B.; Huober, J.; Schoenenberger, A.; Pagani, O.; Luethi, J.; Simcock, M.; Giobbie-Hurder, A.; Genton, C.; Aebi, S.] Kantonsspital Aarau, Aarau, Switzerland. [Zaman, K.; Thuerlimann, B.; Huober, J.; Schoenenberger, A.; Pagani, O.; Luethi, J.; Simcock, M.; Giobbie-Hurder, A.; Genton, C.; Aebi, S.] Oncol Inst So Switzerland, Lugano, Switzerland. [Zaman, K.; Thuerlimann, B.; Huober, J.; Schoenenberger, A.; Pagani, O.; Luethi, J.; Simcock, M.; Giobbie-Hurder, A.; Genton, C.; Aebi, S.] Oncol Hosp Thun, Thun, Switzerland. [Zaman, K.; Thuerlimann, B.; Huober, J.; Schoenenberger, A.; Pagani, O.; Luethi, J.; Simcock, M.; Giobbie-Hurder, A.; Genton, C.; Aebi, S.] SAKK, Coordinating Ctr, Bern, Switzerland. [Zaman, K.; Thuerlimann, B.; Huober, J.; Schoenenberger, A.; Pagani, O.; Luethi, J.; Simcock, M.; Giobbie-Hurder, A.; Genton, C.; Aebi, S.] IBCSG Stat Ctr, Dana Farber Canc Inst, Boston, MA USA. [Zaman, K.; Thuerlimann, B.; Huober, J.; Schoenenberger, A.; Pagani, O.; Luethi, J.; Simcock, M.; Giobbie-Hurder, A.; Genton, C.; Aebi, S.; SAKK] Univ Hosp Bern, CH-3010 Bern, Switzerland. RI Aebi, Stefan/F-2004-2010 OI Aebi, Stefan/0000-0002-3383-9449 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 545 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606601254 PM 27960660 ER PT J AU Zhang, W Dahlberg, SE Yang, D Sandler, AB Brahmer, JR Schiller, JH Carbone, DP Johnson, DH Lenz, H AF Zhang, W. Dahlberg, S. E. Yang, D. Sandler, A. B. Brahmer, J. R. Schiller, J. H. Carbone, D. P. Johnson, D. H. Lenz, H. TI Genetic variants in angiogenesis pathway associated with clinical outcome in NSCLC patients (pts) treated with bevacizumab in combination with carboplatin and paclitaxel: Subset pharmacogenetic analysis of ECOG 4599 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ So Calif, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Johns Hopkins Univ, SKCCC, Baltimore, MD USA. SW Texas State Univ, Dallas, TX USA. Vanderbilt Univ, Ctr Canc, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 8032 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606605234 ER PT J AU Zhu, AX Meyerhardt, JA Blaszkowsky, LS Muzikansky, A Abrams, TA Chan, JA Enzinger, PC Bhargava, P Kwak, EL Sahani, DV AF Zhu, A. X. Meyerhardt, J. A. Blaszkowsky, L. S. Muzikansky, A. Abrams, T. A. Chan, J. A. Enzinger, P. C. Bhargava, P. Kwak, E. L. Sahani, D. V. TI Phase II and fluorodeoxyglucose positron emission tomography (FDG-PET) study in patients with advanced biliary tract cancers (BTCs) receiving bevacizumab (B) in combination with gemcitabine (GEM) and oxaliplatin (OX) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA 4578 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606603168 PM 27963071 ER PT J AU Pazyra-Murphy, MF Hans, A Courchesne, SL Karch, C Cosker, KE Heerssen, HM Watson, FL Kim, T Greenberg, ME Segal, RA AF Pazyra-Murphy, Maria F. Hans, Aymeric Courchesne, Stephanie L. Karch, Christoph Cosker, Katharina E. Heerssen, Heather M. Watson, Fiona L. Kim, Taekyung Greenberg, Michael E. Segal, Rosalind A. TI A Retrograde Neuronal Survival Response: Target-Derived Neurotrophins Regulate MEF2D and bcl-w SO JOURNAL OF NEUROSCIENCE LA English DT Article ID NERVE GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; SYMPATHETIC NEURONS; TRANSCRIPTION FACTOR; DEPENDENT REGULATION; SIGNALING ENDOSOMES; LATERAL-SCLEROSIS; LOCAL-CONTROL; AXON GROWTH; ALSIN GENE AB Survival and maturation of dorsal root ganglia sensory neurons during development depend on target-derived neurotrophins. These target-derived signals must be transmitted across long distances to alter gene expression. Here, we address the possibility that long-range retrograde signals initiated by target-derived neurotrophins activate a specialized transcriptional program. The transcription factor MEF2D is expressed in sensory neurons; we show that expression of this factor is induced in response to target-derived neurotrophins that stimulate the distal axons. We demonstrate that MEF2D regulates expression of an anti-apoptotic bcl-2 family member, bcl-w. Expression of mef2d and bcl-w is stimulated in response to activation of a Trk-dependent ERK5/MEF2 pathway, and our data indicate that this pathway promotes sensory neuron survival. We find that mef2d and bcl-w are members of a larger set of retrograde response genes, which are preferentially induced by neurotrophin stimulation of distal axons. Thus, activation of an ERK5/MEF2D transcriptional program establishes and maintains the cellular constituents of functional sensory circuits. C1 [Pazyra-Murphy, Maria F.; Hans, Aymeric; Courchesne, Stephanie L.; Karch, Christoph; Cosker, Katharina E.; Heerssen, Heather M.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Pazyra-Murphy, Maria F.; Hans, Aymeric; Courchesne, Stephanie L.; Karch, Christoph; Cosker, Katharina E.; Heerssen, Heather M.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Pazyra-Murphy, Maria F.; Hans, Aymeric; Courchesne, Stephanie L.; Karch, Christoph; Cosker, Katharina E.; Heerssen, Heather M.; Watson, Fiona L.; Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Watson, Fiona L.] Washington & Lee Univ, Dept Biol, Lexington, VA 24450 USA. [Watson, Fiona L.] Washington & Lee Univ, Neurosci Program, Lexington, VA 24450 USA. [Kim, Taekyung; Greenberg, Michael E.] Childrens Hosp, Dept Neurobiol, Boston, MA 02115 USA. RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM Rosalind_segal@dfci.harvard.edu FU National Institutes of Health (NIH); MacGregor (University of California, Irvine, Irvine, CA) FX This work was supported by grants from the National Institutes of Health (NIH) (R.A.S., M.E.G.). We thank Grant MacGregor (University of California, Irvine, Irvine, CA), Susan Corey (The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia), and Steve Gutkind (NIH) for the generous gifts of reagents. We thank Todd Golub for advice. We thank Erin Berry, Kelly Dakin, Parizad Bilimoria, and Athar Malik for technical assistance. NR 70 TC 40 Z9 41 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 20 PY 2009 VL 29 IS 20 BP 6700 EP 6709 DI 10.1523/JNEUROSCI.0233-09.2009 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 448GY UT WOS:000266252300031 PM 19458239 ER PT J AU Hicks, GE Morone, N Weiner, DK AF Hicks, Gregory E. Morone, Natalia Weiner, Debra K. TI Degenerative Lumbar Disc and Facet Disease in Older Adults Prevalence and Clinical Correlates SO SPINE LA English DT Article DE chronic low back pain; aging; degenerative disc disease; degenerative facet disease ID LOW-BACK-PAIN; TRUNK MUSCLE COMPOSITION; PHYSICAL FUNCTION; BODY-COMPOSITION; DISABILITY; SPINE; HEALTH; ARTHROSIS; OSTEOARTHRITIS; QUESTIONNAIRE AB Study Design. A case-control study of older adults with and without chronic low back pain (CLBP). Objective. Compare and describe the radiographic severity of degenerative disc and facet disease in the lumbosacral spine of community-dwelling older adults with and without CLBP and to examine the relationship between spinal pathology and pain. Summary of Background Data. Degenerative spinal pathology is often implicated as the primary reason for CLBP in older adults. Despite evidence that spinal pathology may be ubiquitous in older adults regardless of pain status, radiography continues to be heavily used in the diagnostic process. Methods. Participants in this case-control study included 162 older adults (>= 65) with CLBP and an age and gender matched pain-free group of 158 people. CLBP was characterized as pain of at least moderate intensity occurring daily or almost everyday for at least 3 months. Radiographic severity of disc and facet disease was graded using a reliable and valid system. Results. Results demonstrated that the presence of degenerative disc and facet pathology in older adults is ubiquitous, regardless of clinical status, with greater than 90% demonstrating some level of degeneration. Higher radiographic severity scores were associated with the presence of CLBP. In fact, presence of severe disc pathology was associated with 2-fold greater odds of having CLBP. But, radiographic severity of disc and facet disease was not associated with pain severity among those with CLBP. Conclusion. From a research perspective, radiographic evaluation of spinal pathology provides additional information about older adults with CLBP compared to pain-free individuals, but its clinical utility for diagnostic purposes is still in question. C1 [Hicks, Gregory E.] Univ Delaware, Dept Phys Therapy, Newark, DE 19716 USA. [Morone, Natalia] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Hicks, GE (reprint author), Univ Delaware, Dept Phys Therapy, 303 McKinly Lab, Newark, DE 19716 USA. EM ghicks@udel.edu FU National Institute on Aging, National Institutes of Health [R01AG018299]; NICHD [1K12HD055931-01]; National Center for Research Resources (NCRR) [KL2 RR024154-03] FX Supported by the National Institute on Aging, National Institutes of Health with a research grant (R01AG018299). Supported by grant number 1K12HD055931-01 (NICHD) (to G. H.) and grant number KL2 RR024154-03 (to N. M.) from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. NR 35 TC 56 Z9 59 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAY 20 PY 2009 VL 34 IS 12 BP 1301 EP 1306 DI 10.1097/BRS.0b013e3181a18263 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 447VQ UT WOS:000266220500011 PM 19455005 ER PT J AU O'Hare, AM Kaufman, JS Covinsky, KE Landefeld, CS McFarland, LV Larson, EB AF O'Hare, Ann M. Kaufman, James S. Covinsky, Kenneth E. Landefeld, C. Seth McFarland, Lynne V. Larson, Eric B. TI Current Guidelines for Using Angiotensin-Converting Enzyme Inhibitors and Angiotensin II-Receptor Antagonists in Chronic Kidney Disease: Is the Evidence Base Relevant to Older Adults? SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; RANDOMIZED CONTROLLED TRIAL; LEFT-VENTRICULAR HYPERTROPHY; DEPENDENT DIABETES-MELLITUS; CHRONIC RENAL-INSUFFICIENCY; URINARY ALBUMIN EXCRETION; PLACEBO-CONTROLLED TRIAL; NONDIABETIC NEPHROPATHIES; CARDIOVASCULAR OUTCOMES; HYPERTENSIVE PATIENTS AB Angiotensin-converting enzyme inhibitors and angiotensin II-receptor antagonists are recommended for patients with chronic kidney disease because these drugs can slow disease progression. Older adults account for a large and growing number of patients with chronic kidney disease. The authors evaluated the relevance to adults older than 70 years of the evidence base for major U. S. practice guidelines for the use of these agents in chronic kidney disease. The authors first examined the representation of older adults in randomized trials that underpin these guidelines, then compared the characteristics of participants in these trials with those of a representative sample of older adults with chronic kidney disease in the general population. The authors found that current guidelines for the use of angiotensin-converting enzyme inhibitors and angiotensin II-receptor antagonists in chronic kidney disease are based on evidence with limited relevance to most persons older than 70 years with this condition. C1 [O'Hare, Ann M.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Grp Hlth Ctr Hlth Studies, Seattle, WA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Vet Affairs Boston Healthcare Syst, Boston, MA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP O'Hare, AM (reprint author), Univ Washington, Dept Med, Div Nephrol, Bldg 100,Room 5B113,1660 S Columbian Way, Seattle, WA 98108 USA. EM ann.ohare@va.gov FU National Institute on Aging [K 1K23AG28980] FX By a Beeson Career Development Award from the National Institute on Aging to Dr. O'Hare (K 1K23AG28980). NR 72 TC 70 Z9 78 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 19 PY 2009 VL 150 IS 10 BP 717 EP U12 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 448TQ UT WOS:000266285300008 PM 19451579 ER PT J AU Gutierrez, OM Januzzi, JL Isakova, T Laliberte, K Smith, K Collerone, G Sarwar, A Hoffmann, U Coglianese, E Christenson, R Wang, TJ deFilippi, C Wolf, M AF Gutierrez, Orlando M. Januzzi, James L. Isakova, Tamara Laliberte, Karen Smith, Kelsey Collerone, Gina Sarwar, Ammar Hoffmann, Udo Coglianese, Erin Christenson, Robert Wang, Thomas J. deFilippi, Christopher Wolf, Myles TI Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease SO CIRCULATION LA English DT Article DE fibroblast growth factor 23; hormones; hypertrophy; kidney ID CORONARY-ARTERY CALCIFICATION; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; NATRIURETIC PEPTIDE; COMPUTED-TOMOGRAPHY; RISK PREDICTION; HEART-FAILURE; FIBROBLAST-GROWTH-FACTOR-23; MORTALITY; PHOSPHATE AB Background-Fibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone. In chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently associated with mortality. Left ventricular hypertrophy and coronary artery calcification are potent risk factors for mortality in CKD, and FGFs have been implicated in the pathogenesis of both myocardial hypertrophy and atherosclerosis. We conducted a cross-sectional study to test the hypothesis that elevated FGF-23 concentrations are associated with left ventricular hypertrophy and coronary artery calcification in patients with CKD. Methods and Results-In this study, 162 subjects with CKD underwent echocardiograms and computed tomography scans to assess left ventricular mass index and coronary artery calcification; echocardiograms also were obtained in 58 subjects without CKD. In multivariable-adjusted regression analyses in the overall sample, increased log FGF-23 concentrations were independently associated with increased left ventricular mass index (5% increase per 1-SD increase in log FGF-23; P=0.01) and risk of left ventricular hypertrophy (odds ratio per 1-SD increase in log FGF-23, 2.1; 95% confidence interval, 1.03 to 4.2). These associations strengthened in analyses restricted to the CKD subjects (11% increase in left ventricular mass index per 1-SD increase in log FGF-23; P=0.01; odds ratio of left ventricular hypertrophy per 1-SD increase in log FGF-23, 2.3; 95% confidence interval, 1.2 to 4.2). Although the highest tertile of FGF-23 was associated with a 2.4-fold increased risk of coronary artery calcification >= 100 versus <100 U compared with the lowest tertile (95% confidence interval, 1.1 to 5.5), the association was no longer significant after multivariable adjustment. Conclusions-FGF-23 is independently associated with left ventricular mass index and left ventricular hypertrophy in patients with CKD. Whether increased FGF-23 is a marker or a potential mechanism of myocardial hypertrophy in CKD requires further study. (Circulation. 2009; 119: 2545-2552.) C1 [Gutierrez, Orlando M.; Smith, Kelsey; Wolf, Myles] Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. [Januzzi, James L.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. [Isakova, Tamara; Laliberte, Karen; Collerone, Gina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nephrol Div,Dept Med, Boston, MA USA. [Sarwar, Ammar; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Coglianese, Erin] Boston Univ, Sch Med, Dept Med, Cardiovasc Med Sect, Boston, MA 02118 USA. [Christenson, Robert] Univ Maryland, Sch Med, Dept Pathol, Dept Med, Baltimore, MD 21201 USA. [deFilippi, Christopher] Univ Maryland, Sch Med, Div Cardiol, Dept Med, Baltimore, MD 21201 USA. RP deFilippi, C (reprint author), Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, CRB C-221,Room 724,1120 NW 14th St, Miami, FL 33136 USA. EM ogutierrez2@med.miami.edu FU NCRR NIH HHS [K23 RR017376, K23 RR017376-05, K23RR017376, K30 RR022292, K30 RR022292-07, K30RR02229207, M01 RR001066, M01RR01066]; NHLBI NIH HHS [R01 HL086875, R01 HL086875-02, R01HL086875]; NIDDK NIH HHS [R01 DK076116, K23 DK081673, K23 DK081673-01, K23DK081673, R01 DK076116-02, R01DK076116] NR 46 TC 392 Z9 419 U1 0 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 19 PY 2009 VL 119 IS 19 BP 2545 EP 2552 DI 10.1161/CIRCULATIONAHA.108.844506 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 447NY UT WOS:000266199400005 PM 19414634 ER PT J AU Mega, JL Close, SL Wiviott, SD Shen, L Hockett, RD Brandt, JT Walker, JR Antman, EM Macias, WL Braunwald, E Sabatine, MS AF Mega, Jessica L. Close, Sandra L. Wiviott, Stephen D. Shen, Lei Hockett, Richard D. Brandt, John T. Walker, Joseph R. Antman, Elliott M. Macias, William L. Braunwald, Eugene Sabatine, Marc S. TI Cytochrome P450 Genetic Polymorphisms and the Response to Prasugrel Relationship to Pharmacokinetic, Pharmacodynamic, and Clinical Outcomes SO CIRCULATION LA English DT Article DE cardiovascular diseases; drugs; genetics ID PERCUTANEOUS CORONARY INTERVENTION; OF-FUNCTION POLYMORPHISM; THIENOPYRIDINE ANTIPLATELET AGENT; 2007 FOCUSED UPDATE; STENT THROMBOSIS; HEALTHY-SUBJECTS; PLATELET REACTIVITY; CLOPIDOGREL RESPONSIVENESS; MYOCARDIAL-INFARCTION; ACTIVE METABOLITE AB Background-Both clopidogrel and prasugrel require biotransformation to active metabolites by cytochrome P450 (CYP) enzymes. Among persons treated with clopidogrel, carriers of reduced-function CYP2C19 alleles have significantly lower levels of active metabolite, diminished platelet inhibition, and higher rates of adverse cardiovascular events. The effect of CYP polymorphisms on the clinical outcomes in patients treated with prasugrel remains unknown. Methods and Results-The associations between functional variants in CYP genes, plasma concentrations of active drug metabolite, and platelet inhibition in response to prasugrel were tested in 238 healthy subjects. We then examined the association of these genetic variants with cardiovascular outcomes in a cohort of 1466 patients with acute coronary syndromes allocated to treatment with prasugrel in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 trial. Among the healthy subjects, no significant attenuation of the pharmacokinetic or the pharmacodynamic response to prasugrel was observed in carriers versus noncarriers of at least 1 reduced-function allele for any of the CYP genes tested (CYP2C19, CYP2C9, CYP2B6, CYP3A5, and CYP1A2). Consistent with these findings, in subjects with acute coronary syndromes treated with prasugrel, no significant associations were found between any of the tested CYP genotypes and risk of cardiovascular death, myocardial infarction, or stroke. Conclusions-Common functional CYP genetic variants do not affect active drug metabolite levels, inhibition of platelet aggregation, or clinical cardiovascular event rates in persons treated with prasugrel. These pharmacogenetic findings are in contrast to observations with clopidogrel, which may explain, in part, the different pharmacological and clinical responses to the 2 medications. (Circulation. 2009; 119: 2553-2560.) C1 [Mega, Jessica L.; Wiviott, Stephen D.; Antman, Elliott M.; Braunwald, Eugene; Sabatine, Marc S.] Brigham & Womens Hosp, TIMI Study Grp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Mega, Jessica L.; Wiviott, Stephen D.; Antman, Elliott M.; Braunwald, Eugene; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA USA. [Close, Sandra L.; Shen, Lei; Brandt, John T.; Macias, William L.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Hockett, Richard D.] Affymetrix, Santa Clara, CA USA. [Walker, Joseph R.] Daiichi Sankyo Inc, Parsippany, NJ USA. RP Mega, JL (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Dept Med, Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM jmega@partners.org FU Daiichi Sankyo Company, Limited; Eli Lilly and Company FX This study was supported by research grants from Daiichi Sankyo Company, Limited and Eli Lilly and Company. NR 42 TC 363 Z9 383 U1 0 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 19 PY 2009 VL 119 IS 19 BP 2553 EP U44 DI 10.1161/CIRCULATIONAHA.109.851949 PG 14 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 447NY UT WOS:000266199400006 PM 19414633 ER PT J AU Thurberg, BL Fallon, JT Mitchell, R Aretz, T Gordon, RE O'Callaghan, MW AF Thurberg, Beth L. Fallon, John T. Mitchell, Richard Aretz, Thomas Gordon, Ronald E. O'Callaghan, Michael W. TI Cardiac Microvascular Pathology in Fabry Disease Evaluation of Endomyocardial Biopsies Before and After Enzyme Replacement Therapy SO CIRCULATION LA English DT Article DE hypercholesterolemia; hypertrophy; ischemia; microcirculation; pathology ID ALPHA-GALACTOSIDASE-A; LOW-DENSITY LIPOPROTEIN; SERUM-LIPOPROTEINS; AGALSIDASE-ALPHA; GLYCOSPHINGOLIPIDS; ATHEROSCLEROSIS; CARDIOMYOPATHY; ACCUMULATION; CHOLESTEROL; INVOLVEMENT AB Background-In classic Fabry patients, accelerated coronary atherosclerosis and left ventricular hypertrophy manifest in the fourth decade; however, signs of cardiovascular disease also are observed later in life in "cardiac variant" patients and symptomatic female heterozygotes. These disturbances are caused by globotriaosylceramide (GL-3) accumulation in the heart resulting from lysosomal alpha-galactosidase A deficiency. Methods and Results-We analyzed pretreatment and posttreatment endomyocardial biopsies from 58 Fabry patients enrolled in a 5-month, phase 3, double-blind, randomized, placebo-controlled trial, followed by a 54-month open-label extension study of recombinant human alpha-galactosidase A. Baseline evaluations revealed GL-3 deposits in interstitial capillary endothelial cells and large, laminated inclusions within cardiomyocytes. In this study, we evaluated microvascular GL-3 clearance; no clearance of GL-3 was observed in the cardiomyocytes during this trial. Five months of recombinant human alpha-galactosidase A treatment in the phase 3 trial resulted in complete microvascular clearance of GL-3 from 72% of treated patients compared with only 3% of placebo patients (P<0.001). The placebo group achieved similar results after 6 months of treatment in the open-label trial. In addition, the capillary endothelium remained free of GL-3 for up to 60 months in 6 of 8 patients who consented to an end-of-study biopsy. Conclusions-The findings suggest that long-term treatment with recombinant human alpha-galactosidase A may halt the progression of vascular pathology and prevent the clinical manifestations of atherosclerotic disease. This histopathological study should be a useful guide for clinicians and pathologists who diagnose and follow Fabry patients. (Circulation. 2009; 119: 2561-2567.) C1 [Thurberg, Beth L.; O'Callaghan, Michael W.] Genzyme Corp, Dept Pathol, Framingham, MA 01701 USA. [Thurberg, Beth L.; O'Callaghan, Michael W.] Genzyme Corp, Dept Preclin Biol, Framingham, MA 01701 USA. [Fallon, John T.; Gordon, Ronald E.] Mt Sinai Sch Med, Dept Pathol, New York, NY USA. [Mitchell, Richard] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Mitchell, Richard] Harvard Univ, Sch Med, Boston, MA USA. [Aretz, Thomas] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Thurberg, BL (reprint author), Genzyme Corp, Dept Pathol, 5 Mt Rd, Framingham, MA 01701 USA. EM Beth.Thurberg@genzyme.com FU Genzyme Corp, Cambridge, Mass FX This study was funded by Genzyme Corp, Cambridge, Mass. NR 38 TC 57 Z9 62 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 19 PY 2009 VL 119 IS 19 BP 2561 EP 2567 DI 10.1161/CIRCULATIONAHA.108.841494 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 447NY UT WOS:000266199400007 PM 19414635 ER PT J AU Arimura, N Kimura, T Nakamuta, S Taya, S Funahashi, Y Hattori, A Shimada, A Menager, C Kawabata, S Fujii, K Iwamatsu, A Segal, RA Fukuda, M Kaibuchi, K AF Arimura, Nariko Kimura, Toshihide Nakamuta, Shinichi Taya, Shinichiro Funahashi, Yasuhiro Hattori, Atsushi Shimada, Akiko Menager, Cine Kawabata, Saeko Fujii, Kayo Iwamatsu, Akihiro Segal, Rosalind A. Fukuda, Mitsunori Kaibuchi, Kozo TI Anterograde Transport of TrkB in Axons Is Mediated by Direct Interaction with Slp1 and Rab27 SO DEVELOPMENTAL CELL LA English DT Article ID NEURONAL POLARITY; RETROGRADE TRANSPORT; HOMOLOGY DOMAIN; CRMP-2; PROTEINS; COMPLEX; GSK-3-BETA; GROWTH; PHOSPHORYLATION; MECHANISMS AB The neurotrophin receptors TrkA, TrkB, and TrkC are localized at the surface of the axon terminus and transmit key signals from brain-derived neurotrophic factor (BDNF) for diverse effects on neuronal survival, differentiation, and axon formation. Trk receptors are sorted into axons via the anterograde transport of vesicles and are then inserted into axonal plasma membranes. However, the transport mechanism remains largely unknown. Here, we show that the Slp1/Rab27B/CRMP-2 complex directly links TrkB to Kinesin-1, and that this association is required for the anterograde transport of TrkB-containing vesicles. The cytoplasmic tail of TrkB binds to Slp1 in a Rab27B-dependent manner, and CRMP-2 connects Slp1 to Kinesin-1. Knockdown of these molecules by siRNA reduces the anterograde transport and membrane targeting of TrkB, thereby inhibiting BDNF-induced ERK1/2 phosphorylation in axons. Our data reveal a molecular mechanism for the selective anterograde transport of TrkB in axons and show how the transport is coupled to BDNF signaling. C1 [Arimura, Nariko; Kimura, Toshihide; Nakamuta, Shinichi; Taya, Shinichiro; Funahashi, Yasuhiro; Hattori, Atsushi; Shimada, Akiko; Menager, Cine; Kawabata, Saeko; Fujii, Kayo; Kaibuchi, Kozo] Nagoya Univ, Grad Sch Med, Dept Cell Pharmacol, Showa Ku, Nagoya, Aichi 4668550, Japan. [Taya, Shinichiro; Funahashi, Yasuhiro; Kaibuchi, Kozo] JST, CREST, Kawaguchi, Saitama 3320012, Japan. [Iwamatsu, Akihiro] Kirin Brewery Co Ltd, Cent Labs Key Technol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. [Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Segal, Rosalind A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Fukuda, Mitsunori] Tohoku Univ, Lab Membrane Trafficking Mechanisms, Dept Dev Biol & Neurosci, Grad Sch Life Sci,Aoba, Sendai, Miyagi 9808578, Japan. RP Kaibuchi, K (reprint author), Nagoya Univ, Grad Sch Med, Dept Cell Pharmacol, Showa Ku, 65 Tsurumai, Nagoya, Aichi 4668550, Japan. EM kaibuchi@med.nagoya-u.ac.jp RI Fukuda, MItsunori/I-1511-2015 FU Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency (JST); Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) [20227006, 17024024, 18700314, 20700332]; Japan Society for the Promotion of Science (JSPS) [15GS0319, 20-9883]; Ministry of Health, Labour and Welfare [18-8] FX We thank R.Y. Tsien (UCSD); M. Igarashi (Niigata University); Y. Fukata (National Institute for Physiological Sciences); T. Suzuki (Hokkaido University); R.D. Burgoyne (University of Liverpool); M. Chao (New York University School of Medicine); and T. Watanabe, M. Takefuji, and N. Mishima (Nagoya University) for helpful discussions and preparation of some materials. We also thank T. Ishii for secretarial and technical assistance. This work was supported by Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency (JST); grant (S) 20227006 from grants-in-aid for scientific research (K.K.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); grant 15GS0319 from grants-in-aid for creative scientific research from the Japan Society for the Promotion of Science (JSPS) (K.K.); grant 17024024 from grants-in-aid for scientific research on priority areas from MEXT (K.K.); a grant-in-aid for GCOE research from MEXT; grant 20-9883 from grants-in-aid for JSPS Fellows (S.N.); grants (B) 18700314 and 20700332 (N.A.) from grants-in-aid for young scientists from MEXT; and research grant 18-8 for Nervous and Mental Disorders from the Ministry of Health, Labour and Welfare. NR 40 TC 85 Z9 89 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAY 19 PY 2009 VL 16 IS 5 BP 675 EP 686 DI 10.1016/j.devcel.2009.03.005 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 449RG UT WOS:000266347100010 PM 19460344 ER PT J AU Hannibal, MC Ruzzo, EK Miller, LR Betz, B Buchan, JG Knutzen, DM Barnett, K Landsverk, ML Brice, A LeGuern, E Bedford, HM Worrall, BB Lovitt, S Appel, SH Andermann, E Bird, TD Chance, PF AF Hannibal, M. C. Ruzzo, E. K. Miller, L. R. Betz, B. Buchan, J. G. Knutzen, D. M. Barnett, K. Landsverk, M. L. Brice, A. LeGuern, E. Bedford, H. M. Worrall, B. B. Lovitt, S. Appel, S. H. Andermann, E. Bird, T. D. Chance, P. F. TI SEPT9 gene sequencing analysis reveals recurrent mutations in hereditary neuralgic amyotrophy SO NEUROLOGY LA English DT Article ID MAMMALIAN SEPTIN; HEREDOFAMILIAL NEURITIS; BRACHIAL PREDILECTION; CHROMOSOME 17Q; HNA LOCUS; NEUROPATHY; DATABASE; COMPLEX; REFINEMENT; EXPRESSION AB Background: Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder that manifests as recurrent, episodic, painful brachial neuropathies. A gene for HNA maps to chromosome 17q25.3 where mutations in SEPT9, encoding the septin-9 protein, have been identified. Objective: To determine the frequency and type of mutations in the SEPT9 gene in a new cohort of 42 unrelated HNA pedigrees. Methods: DNA sequencing of all exons and intron-exon boundaries for SEPT9 was carried out in an affected individual in each pedigree from our HNA cohort. Genotyping using microsatellite markers spanning the SEPT9 gene was also used to identify pedigrees with a previously reported founder haplotype. Results: Two missense mutations were found: c.262C > T (p.Arg88Trp) in seven HNA pedigrees and c.278C > T (p.Ser93Phe) in one HNA pedigree. Sequencing of other known exons in SEPT9 detected no additional disease-associated mutations. A founder haplotype, without defined mutations in SEPT9, was present in seven pedigrees. Conclusions: We provide further evidence that mutation of the SEPT9 gene is the molecular basis of some cases of hereditary neuralgic amyotrophy (HNA). DNA sequencing of SEPT9 demonstrates a restricted set of mutations in this cohort of HNA pedigrees. Nonetheless, sequence analysis will have an important role in mutation detection in HNA. Additional techniques will be required to find SEPT9 mutations in an HNA founder haplotype and other pedigrees. Neurology (R) 2009; 72: 1755-1759 C1 [Hannibal, M. C.] Univ Washington, Sch Med, Dept Pediat, Div Genet & Dev Med,Neurogenet Lab,Hlth Sci RR236, Seattle, WA 98195 USA. [Bird, T. D.; Chance, P. F.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. [Bird, T. D.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Hannibal, M. C.; Chance, P. F.] Seattle Childrens Hosp, Seattle, WA USA. [Bird, T. D.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Brice, A.; LeGuern, E.] Univ Paris 06, Pitie Salpetriere Hosp, AP HP,Pitie Salpetriere Med Sch, Dept Genet & Cytogenet,INSERM,UMR S679, Paris, France. [Bedford, H. M.] N York Gen Hosp, Genet Programme, Toronto, ON, Canada. [Worrall, B. B.] Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA. [Worrall, B. B.] Univ Virginia Hlth Syst, Dept Publ Hlth Sci, Charlottesville, VA USA. [Lovitt, S.] Methodist Neurol Inst, Houston, TX USA. [Andermann, E.] McGill Univ, Dept Neurol & Neurosurg, Neurogenet Unit, Montreal Neurol Hosp & Inst, Montreal, PQ H3A 2T5, Canada. [Andermann, E.] McGill Univ, Dept Human Genet, Neurogenet Unit, Montreal Neurol Hosp & Inst, Montreal, PQ H3A 2T5, Canada. [Appel, S. H.] Dept Neurol, Houston, TX USA. RP Hannibal, MC (reprint author), Univ Washington, Sch Med, Dept Pediat, Div Genet & Dev Med,Neurogenet Lab,Hlth Sci RR236, 1959 NE Pacific St,Box 356320, Seattle, WA 98195 USA. EM mhanni@u.washington.edu FU NIH ( National Institute of Neurological Disorders and Stroke) [NS38181]; The Neuropathy Association, New York, NY; Allan and Phyllis Treuer Endowed Chair for Genetics and Development FX Supported by funds from the NIH ( National Institute of Neurological Disorders and Stroke), NS38181 ( P. F. C. and M. C. H.); The Neuropathy Association, New York, NY ( M. C. H. and P. F. C.); and the Allan and Phyllis Treuer Endowed Chair for Genetics and Development ( P. F. C.). NR 36 TC 21 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 19 PY 2009 VL 72 IS 20 BP 1755 EP 1759 DI 10.1212/WNL.0b013e3181a609e3 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 447EB UT WOS:000266173300008 PM 19451530 ER PT J AU Han, G Gupta, SD Gable, K Niranjanakumari, S Moitra, P Eichler, F Brown, RH Harmon, JM Dunn, TM AF Han, Gongshe Gupta, Sita D. Gable, Kenneth Niranjanakumari, Somashekarappa Moitra, Prasun Eichler, Florian Brown, Robert H., Jr. Harmon, Jeffrey M. Dunn, Teresa M. TI Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE long-chain bases; sphingolipids; HSAN1; ssSPT ID HEREDITARY SENSORY NEUROPATHY; SPHINGOLIPID SYNTHESIS; INDUCED APOPTOSIS; IN-VIVO; GENE; PROTEIN; CLONING; YEAST; LCB1; ENZYME AB Serine palmitoyltransferase (SPT) catalyzes the first committed step in sphingolipid biosynthesis. In yeast, SPT is composed of a heterodimer of 2 highly-related subunits, Lcb1p and Lcb2p, and a third subunit, Tsc3p, which increases enzyme activity markedly and is required for growth at elevated temperatures. Higher eukaryotic orthologs of Lcb1p and Lcb2p have been identified, but SPT activity is not highly correlated with coexpression of these subunits and no ortholog of Tsc3p has been identified. Here, we report the discovery of 2 proteins, ssSPTa and ssSPTb, which despite sharing no homology with Tsc3p, each substantially enhance the activity of mammalian SPT expressed in either yeast or mammalian cells and therefore define an evolutionarily conserved family of low molecular weight proteins that confer full enzyme activity. The 2 ssSPT isoforms share a conserved hydrophobic central domain predicted to reside in the membrane, and each interacts with both hLCB1 and hLCB2 as assessed by positive split ubiquitin 2-hybrid analysis. The presence of these small subunits, along with 2 hLCB2 isofoms, suggests that there are 4 distinct human SPT isozymes. When each SPT isozyme was expressed in either yeast or CHO LyB cells lacking endogenous SPT activity, characterization of their in vitro enzymatic activities, and long-chain base (LCB) profiling revealed differences in acyl-CoA preference that offer a potential explanation for the observed diversity of LCB seen in mammalian cells. C1 [Han, Gongshe; Gupta, Sita D.; Gable, Kenneth; Niranjanakumari, Somashekarappa; Dunn, Teresa M.] Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA. [Moitra, Prasun; Harmon, Jeffrey M.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. [Eichler, Florian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci,Dept Neurol, Boston, MA 02114 USA. [Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. RP Dunn, TM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM tdunn@usuhs.mil OI Harmon, Jeffrey/0000-0001-7833-931X FU United States Public Health Service [NS47717]; National Institutes of Health FX We thank Kentaro Hanada (Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo, Japan) for the CHO LyB cells. This work was supported by United States Public Health Service Grant NS47717 awarded by National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 27 TC 77 Z9 84 U1 2 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 19 PY 2009 VL 106 IS 20 BP 8186 EP 8191 DI 10.1073/pnas.0811269106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 447RH UT WOS:000266209000020 PM 19416851 ER PT J AU Rivera, MN Kim, WJ Wells, J Stone, A Burger, A Coffman, EJ Zhang, JM Haber, DA AF Rivera, Miguel N. Kim, Woo Jae Wells, Julie Stone, Amanda Burger, Alexa Coffman, Erik J. Zhang, Jianmin Haber, Daniel A. TI The tumor suppressor WTX shuttles to the nucleus and modulates WT1 activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer biology; subcellular localization; tumor suppression ID WILMS-TUMOR; BETA-CATENIN; GENE; RELAXATION; ACTIVATION; MUTATIONS; PROTEIN; KIDNEY AB WTX encodes a tumor suppressor gene inactivated in Wilms tumor and recently implicated in WNT signaling through enhancement of cytoplasmic beta-catenin (CTNNB1) degradation. Here, we report that WTX translocates to the nucleus, a property that is modified by an endogenous splicing variant and is modulated by a nuclear export inhibitor. WTX is present in distinct subnuclear structures and co-localizes with the paraspeckle marker p54NRB/NONO, suggesting a role in transcriptional regulation. Notably, WTX binds WT1, another Wilms tumor suppressor and stem cell marker that encodes a zinc-finger transcription factor, and enhances WT1-mediated transcription of Amphiregulin, an endogenous target gene. Together, these observations suggest a role for WTX in nuclear pathways implicated in the transcriptional regulation of cellular differentiation programs. C1 [Rivera, Miguel N.; Kim, Woo Jae; Wells, Julie; Stone, Amanda; Burger, Alexa; Coffman, Erik J.; Zhang, Jianmin; Haber, Daniel A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Haber, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, 149 13th St,Room 7-101, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu FU National Institutes of Health [R37CA058596, PO1CA101942, K08DK080175, T32CA009216]; Hood Foundation; Burroughs Wellcome Fund FX This work was supported by the Howard Hughes Medical Institute and by grants from the National Institutes of Health (D. A. H., R37CA058596, PO1CA101942; M. N. R., K08DK080175; W. J. K., T32CA009216), the Hood Foundation, and the Burroughs Wellcome Fund (M. N. R.). The authors would like to thank Dr. Jonathan Whetstine for help with confocal microscopy and valuable discussions. NR 27 TC 39 Z9 47 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 19 PY 2009 VL 106 IS 20 BP 8338 EP 8343 DI 10.1073/pnas.0811349106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 447RH UT WOS:000266209000046 PM 19416806 ER PT J AU Arumugam, M Garg, H Ajithkumar, T Shanmugam, A AF Arumugam, Muthuvel Garg, Hari Ajithkumar, Thangappan Shanmugam, A. TI Antiproliferative heparin (glycosaminoglycans) isolated from giant clam (Tridacna maxima) and green mussel (Perna viridis) SO AFRICAN JOURNAL OF BIOTECHNOLOGY LA English DT Article DE heparin; antiproliferative activity; giant clam; green mussel; glycosaminoglycan ID SMOOTH-MUSCLE-CELLS; SULFATED MUCOPOLYSACCHARIDES; ANTICOAGULANT; PURIFICATION; MOLLUSKS AB Heparin was isolated from two bivalve mollusks, Tridacna maxima (giant clam) and Perna viridis (green mussel). The isolated heparin was quantified in crude as well as purified samples and they were estimated as 2.72 and 2.2 g/kg (in crude) and 260 and 248 mg/g (in purified samples) in T. maxima and P. viridis, respectively. The antiproliferative activity of both the samples performed with pulmonary artery smooth muscle cells (PASMC) indicate a dose dependent manner. Among these two clams, P. viridis heparin showed higher antiproliferative activity than that of T. maxima. C1 [Arumugam, Muthuvel; Ajithkumar, Thangappan; Shanmugam, A.] Annamalai Univ, Ctr Adv Study Marine Biol, Porto Novo, India. [Garg, Hari] Mass Gen Hosp, Pulm & Crit Unit, Boston, MA 02114 USA. RP Arumugam, M (reprint author), Annamalai Univ, Ctr Adv Study Marine Biol, Porto Novo, India. EM aru_hep@yahoo.com NR 20 TC 2 Z9 4 U1 1 U2 4 PU ACADEMIC JOURNALS PI VICTORIA ISLAND PA P O BOX 5170-00200 NAIROBI, VICTORIA ISLAND, LAGOS 73023, NIGERIA SN 1684-5315 J9 AFR J BIOTECHNOL JI Afr. J. Biotechnol. PD MAY 18 PY 2009 VL 8 IS 10 BP 2394 EP 2396 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 453AH UT WOS:000266581800062 ER PT J AU Looby, SED Collins, M Lee, H Grinspoon, S AF Looby, Sara E. Dolan Collins, Merredith Lee, Hang Grinspoon, Steven TI Effects of long-term testosterone administration in HIV-infected women: a randomized, placebo-controlled trial SO AIDS LA English DT Article DE AIDS; HIV; testosterone; women ID ANDROGEN-DEFICIENT WOMEN; POSTMENOPAUSAL WOMEN; BODY-COMPOSITION; WASTING SYNDROME; BONE-DENSITY; DOUBLE-BLIND; IMMUNODEFICIENCY; HYPOPITUITARISM; REPLACEMENT; WEIGHT AB Objective: Androgen deficiency is common in HIV-infected women. We investigated the long-term effects of transdermal testosterone on body composition, bone mineral density, quality of life, and safety. Design: Twenty-five HIV-infected women with free testosterone below the median (<= 3 pg/ml) of the female normal range were randomized to receive transdermal testosterone (300 mu g twice weekly) or identical placebo over 18 months. Results: Women demonstrated low androgen levels (1.3 +/- 0.1 pg/ml) with relatively low weight (22.8 +/- 0.6 kg/m(2)) and low bone mineral density (-0.61 +/- 0.17 SD hip T score) at baseline. No statistically significant differences were seen between the groups at baseline. The discontinuation rate was 16% and did not differ between treatment groups (P = 0.24). Free testosterone by equilibrium dialysis increased over 18 months (7.9 +/- 1.8 vs. 0.3 +/- 0.4 pg/ml; P = 0.002, testosterone vs. placebo). Testosterone was well tolerated and did not affect lipids, liver, or safety indices. Lean mass (11.8 +/- 0.5 vs. 0.8 +/- 0.9 kg; P = 0.04) and BMI (1.6 +/- 0.4 vs. 0.8 +/- 0.6 kg/m(2); P = 0.03, testosterone vs. placebo) increased in response to testosterone, whereas fat mass remained unchanged. Testosterone increased bone mineral density at the hip (0.01 +/- 0.01 vs. -0.01 +/- 0.01 g/cm(2); P = 0.02) and trochanter (0.01 +/- 0.01 vs. -0.02 +/- 0.01 g/cm(2); P = 0.01, testosterone vs. placebo). Testosterone significantly improved depression indices (-6.8 +/- 2.2 vs. -1.9 +/- 3.1; P = 0.02) and problems affecting sexual function (-1.8 +/- 0.8 vs. 0.5 +/- 0.5; P = 0.01, testosterone vs. placebo). Conclusion: Long-term testosterone administration was well tolerated in HIV-infected women and resulted in significant improvements in body composition, bone mineral density, and quality of life indices. Further evaluation of the safety and efficacy of testosterone use among HIV-infected women is warranted. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Looby, Sara E. Dolan; Collins, Merredith; Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Lee, Hang; Grinspoon, Steven] Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NIH [DK-R01 054167, M01-RR-01.066, 1 UL1 RR025758-01]; Harvard Clinical and Translational Science Center; National Center for Research Resources FX This study was funded by NIH DK-R01 054167 (S.G.), M01-RR-01.066, 1, UL1 RR025758-01, and the Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health. Procter and Gamble provided transdermal testosterone and blinded placebo patches but did not participate in study design, analysis, or manuscript preparation. NR 20 TC 9 Z9 9 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD MAY 15 PY 2009 VL 23 IS 8 BP 951 EP 959 DI 10.1097/QAD.0b013e3283299145 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446MH UT WOS:000266125200009 ER PT J AU Dasgupta, A Steinhubl, SR Bhatt, DL Berger, PB Shao, MY Mak, KH Fox, KAA Montalescot, G Weber, MA Haffner, SM Dimas, AP Steg, PG Topol, EJ AF Dasgupta, Arijit Steinhubl, Steven R. Bhatt, Deepak L. Berger, Peter B. Shao, Mingyuan Mak, Koon-Hou Fox, Keith A. A. Montalescot, Gilles Weber, Michael A. Haffner, Steven M. Dimas, Alexios P. Steg, P. Gabriel Topol, Eric J. CA CHARISMA Investigators TI Clinical Outcomes of Patients With Diabetic Nephropathy Randomized to Clopidogrel Plus Aspirin Versus Aspirin Alone (A post hoc Analysis of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA] Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; ANTIPLATELET THERAPY; RENAL-FUNCTION; EVENTS; PHARMACOKINETICS; CYTOCHROME-P450; HEMODIALYSIS; INHIBITION; FAILURE AB No prospective randomized trial has specifically examined the long-term outcomes of clopidogrel use in patients with chronic kidney disease. This study aimed to determine the risks and benefits of long-term clopidogrel administration in patients with diabetic nephropathy, the most common form of chronic kidney disease. We performed a post hoc analysis of the CHARISMA trial, which randomly assigned patients without active acute coronary syndrome, but with established atherosclerotic disease (symptomatic) or multiple risk factors for atherosclerotic disease (asymptomatic), to clopidogrel plus aspirin versus placebo plus aspirin. All CHARISMA patients (n = 15,603) were separated into the 3 groups: nondiabetic patients, diabetic patients without nephropathy, and diabetic patients with nephropathy. Within each group, outcomes of patients randomly assigned to clopidogrel were compared with those of patients randomly assigned to placebo. Outcomes in the prespecified CHARISMA subgroups of asymptomatic and symptomatic patients were also compared with respect to study drug assignment and nephropathy status. Patients with nephropathy who received clopidogrel had no difference in bleeding, but experienced significantly increased cardiovascular (CV) and overall mortality compared with those randomly assigned to placebo. There were no differences in bleeding, overall mortality, or CV mortality for nondiabetic or diabetic patients without nephropathy who received clopidogrel versus placebo. In the asymptomatic cohort, patients with nephropathy randomly assigned to clopidogrel had significantly increased overall and CV mortality compared with placebo, whereas asymptomatic patients without nephropathy randomly assigned to clopidogrel had no significant mortality difference compared with placebo. In conclusion, this post hoc analysis suggested that clopidogrel may be harmful in patients with diabetic nephropathy. Additional studies are needed to investigate this possible interaction. (c) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;103:1359-1363) C1 [Dasgupta, Arijit] Univ Kentucky, Gill Heart Inst, Lexington, KY 40506 USA. [Steinhubl, Steven R.; Berger, Peter B.] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA. [Steinhubl, Steven R.] Medicines Co, Zurich, Switzerland. VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Shao, Mingyuan] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Mak, Koon-Hou] Gleneagles Med Ctr, Singapore, Singapore. [Fox, Keith A. A.] Univ & Royal Infirm Edinburgh, Edinburgh, Midlothian, Scotland. [Montalescot, Gilles] CHU Pitie Salpetriere, Inst Cardiol, Paris, France. [Weber, Michael A.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Dimas, Alexios P.] Hygeia Hosp, Athens, Greece. [Steg, P. Gabriel] Hop Bichat Claude Bernard, F-75877 Paris, France. [Topol, Eric J.] Scripps Clin, Scripps Translat Sci Inst, La Jolla, CA 92037 USA. RP Dasgupta, A (reprint author), Univ Kentucky, Gill Heart Inst, Lexington, KY 40506 USA. EM adasg2@email.uky.edu RI Walker, Philip/F-3034-2010 NR 15 TC 58 Z9 63 U1 1 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2009 VL 103 IS 10 BP 1359 EP 1363 DI 10.1016/j.amjcard.2009.01.342 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 450PN UT WOS:000266413400005 PM 19427428 ER PT J AU Lin, Y Avruch, J AF Lin, Yenshou Avruch, Joseph TI pTOM, a vector for expressing two proteins in mammalian cells SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID ENHANCER; PROMOTER; GENE AB We developed a pTOM construct that can express two proteins in a cell. Using pTOM ensures that two polypeptide-encoding nucleotide sequences are simultaneously transfected into the same cell. The ability to simultaneously express two separate polypeptide-encoding nucleotide sequences from the same vector in the same cell allows the user to determine the relationship between the two proteins. Another advantage is that one of the proteins can be used as a transfection marker/selector. The vector contains multiple clonings sites for insertions of polypeptide-encoding nucleotide sequences. Positive clones can be easily selected when performing cloning using ampicillin. Overall, this vector provides a convenient way to express dual proteins in a single mammalian cell. (C) 2009 Elsevier Inc. All rights reserved. C1 [Lin, Yenshou] Natl Taiwan Normal Univ, Dept Life Sci, Taipei 116, Taiwan. [Lin, Yenshou; Avruch, Joseph] Harvard Univ, Sch Med, Diabet Unit, Boston, MA 02114 USA. [Lin, Yenshou; Avruch, Joseph] Harvard Univ, Dept Mol Biol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Lin, Yenshou; Avruch, Joseph] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Lin, Y (reprint author), Natl Taiwan Normal Univ, Dept Life Sci, 88 Ting Chou Rd,Sect 4, Taipei 116, Taiwan. EM yenshoulin@ntnu.edu.tw FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-14] NR 7 TC 0 Z9 0 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAY 15 PY 2009 VL 388 IS 2 BP 353 EP 355 DI 10.1016/j.ab.2009.03.015 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 444MH UT WOS:000265984600026 PM 19303393 ER PT J AU Rogers, NH Witczak, CA Hirshman, MF Goodyear, LJ Greenberg, AS AF Rogers, Nicole H. Witczak, Carol A. Hirshman, Michael F. Goodyear, Laurie J. Greenberg, Andrew S. TI Estradiol stimulates Akt, AMP-activated protein kinase (AMPK) and TBC1D1/4, but not glucose uptake in rat soleus SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Estrogen; ICI 182,780; Skeletal muscle; AS160; Insulin signaling ID MOUSE SKELETAL-MUSCLE; ESTROGEN; INSULIN; CONTRACTION; RECEPTOR; SENSITIVITY; TRANSPORT; ADENOSINE; PATHWAYS; REQUIRES AB Post-menopausal women exhibit decreases in circulating estrogen levels and whole body insulin sensitivity, suggesting that estrogen regulates skeletal muscle glucose disposal. Thus, we assessed whether estrogen stimulates glucose uptake or enhances insulin sensitivity in skeletal muscle. Ex vivo muscle Stimulation with 17 beta-estradiol (10 nM) resulted in a rapid (<= 10 min) increase in the phosphorylation of Akt, AMP-activated protein kinase (AMPK), and TBC1D1/4, key signaling Proteins that regulate glucose uptake in muscle. Treatment with the estrogen receptor antagonist, ICI 182,780, only partly inhibited signaling, suggesting both an estrogen receptor-dependent and independent mechanism of estradiol action. 17 beta-Estradiol did not stimulate ex vivo muscle [(3)H]-2-deoxyglucose Uptake or enhance insulin-induced glucose Uptake, demonstrating discordance between the estradiol-induced stimulation of signaling proteins and muscle glucose uptake. This study is the first to demonstrate that estradiol stimulates Akt, AMPK, and TBC1D1/4 in intact skeletal muscle, but surprisingly, estradiol does not stimulate muscle glucose uptake. (C) 2009 Elsevier Inc. All rights reserved. C1 [Rogers, Nicole H.; Greenberg, Andrew S.] Tufts Univ, JM USDA HNRCA, Boston, MA 02111 USA. [Witczak, Carol A.; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Metab Sect, Boston, MA 02215 USA. RP Greenberg, AS (reprint author), Tufts Univ, JM USDA HNRCA, HNRCA Room 603,711 Washington St, Boston, MA 02111 USA. EM Andrew.greenberg@tufts.edu RI Rogers, nicole/J-4838-2012 FU United States Department of Agriculture, Tufts Medical Center, NIDDK, American Diabetes Association [5819507707, T32DK062032, 50647]; National Institutes of Health [R01 AR45670] FX This work was supported by grants from the United States Department of Agriculture (5819507707), Tufts Medical Center (T32DK062032), NIDDK (50647), and American Diabetes Association to ASG: National Institutes of Health (R01 AR45670) and American Diabetes Association to LJG. NR 24 TC 43 Z9 46 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 15 PY 2009 VL 382 IS 4 BP 646 EP 650 DI 10.1016/j.bbrc.2009.02.154 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 444OB UT WOS:000265989200002 PM 19265681 ER PT J AU Weinick, RM Bristol, SJ DesRoches, CM AF Weinick, Robin M. Bristol, Steffanie J. DesRoches, Catherine M. TI Urgent care centers in the US: Findings from a national survey SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID RETAIL CLINICS; 7 COUNTRIES; VISITS; EXPERIENCES; PHYSICIANS; SYSTEMS AB Background: Due to long waits for primary care appointments and extended emergency department wait times, newer sites for episodic primary care services, such as urgent care centers, have developed. However, little is known about these centers. The purpose of this study is to provide information about the organization and functioning of urgent care centers based on a nationally representative U.S. sample. Methods: We conducted a mail survey with telephone follow-up of urgent care centers identified via health insurers' websites, internet searches, and a trade association mailing list. Descriptive statistics are presented. Results: Urgent care centers are open beyond typical office hours, and their scope of services is broader than that of many primary care offices. While these characteristics are similar to hospital emergency departments, such centers employ significant numbers of family physicians. The payer distribution is similar to that of primary care, and physicians' average salaries are comparable to those for family physicians overall. Urgent care centers report early adoption of electronic health records, though our findings are qualified by a lack of strictly comparable data. Conclusion: While their hours and scope of services reflect some characteristics of emergency departments, urgent care centers are in many ways similar to family medicine practices. As the health care system evolves to cope with expanding demands in the face of limited resources, it is unclear how patients with episodic care needs will be treated, and what role urgent care centers will play in their care. C1 [Weinick, Robin M.] RAND Corp, Arlington, VA USA. [Bristol, Steffanie J.; DesRoches, Catherine M.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [DesRoches, Catherine M.] Harvard Univ, Sch Med, Boston, MA USA. RP Weinick, RM (reprint author), RAND Corp, Arlington, VA USA. EM Robin_Weinick@rand.org; sbristol@partners.org; cdesroches@partners.org FU Urgent Care Association of America FX Financial support for this study was provided by a grant from the Urgent Care Association of America. An earlier version was presented at the Annual Convention of the Urgent Care Association of America, New Orleans, LA, May 2008. The Urgent Care Association of America Benchmarking Committee provided valuable assistance in designing the content of the survey. The authors would like to thank Jessica Marder for her assistance in preparing the sample frame, and Guideline for conducting the fieldwork. NR 31 TC 18 Z9 18 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD MAY 15 PY 2009 VL 9 AR 79 DI 10.1186/1472-6963-9-79 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 454OW UT WOS:000266693000001 PM 19445656 ER PT J AU Lin, MC Burkholder, KA Viswanathan, AN Neuberg, D Mutter, GL AF Lin, Ming-Chieh Burkholder, Kyla A. Viswanathan, Akila N. Neuberg, Donna Mutter, George L. TI Involution of Latent Endometrial Precancers by Hormonal and Nonhormonal Mechanisms SO CANCER LA English DT Article DE endometrium; latent precancer; PTEN; oral contraceptive; intrauterine device ID PTEN EXPRESSION; INTRAUTERINE-DEVICE; CARCINOMA; PROGRESSION; NEOPLASIA; CANCER; TISSUE; MARKER; SYSTEM AB BACKGROUND: Inactivation of the PTEN suppressor gene has been shown to occur in the majority of endometrial cancer cases. Somatic PTEN inactivation by deletion and/or mutation, the first detectible change of endometrial carcinogenesis, has been reported to occur at a high frequency in the endometrium of normal premenopausal women, although few of these cases progress to cancer. It was hypothesized that the 50% to 60% reduced cancer risk attributed to oral contraceptives (OCPs) and intrauterine devices (IUDs) occurred in part through their activity as negative selection factors for these subclinical mutated glands. METHODS: A total of 71 women with a history of OCP use and 80 with a history of IUD use were age matched with 191 and 119 controls, respectively. Endometrial biopsy specimens were immunostained for PTEN, and each was scored for the presence or absence of PTEN-null glands (latent precancer). RESULTS: The frequency of latent precancers was found to be significantly reduced in OCP-exposed (13%; odds ratio [OR], 0.19 [P <.001]) and IUD-exposed (18%; OR, 0.42 EP = .015]) women compared with respective matched controls (43% and 34%). The presence or absence of endometritis did not appear to be significantly correlated with PTEN status within the IUD-exposed group (P = .24). CONCLUSIONS: Normal-appearing PTEN mutated endometrial glands, which are highly prevalent in the normal population, may be targets of endometrial cancer risk-modulating exposures. Some exposures reported to diminish the incidence of endometrial cancer in epidemiologic outcome studies, including OCP and IUD use, are associated with a proportionate decline in the frequency of latent precancers. Involution of pre-existing enclometrial latent precancers, as evaluated by PTEN analysis, may provide an accessible surrogate marker for long-term enclometrial cancer risk. Cancer 2009;115:2111-8.(C) 2009 American Cancer Society. C1 [Mutter, George L.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Lin, Ming-Chieh] Natl Taiwan Univ, Coll Med, Dept Pathol, Natl Taiwan Univ Hosp, Taipei, Taiwan. [Viswanathan, Akila N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Mutter, GL (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. EM gmutter@rics.bwh.harvard.edu RI Mutter, George/C-5819-2009 FU National Institutes of Health [RO1-CA100833]; NHRI Physician Scientist Award, Taiwan FX Supported by National Institutes of Health grant RO1-CA100833 (G. Mutter), and a NHRI Physician Scientist Award, Taiwan (M. Lin). NR 20 TC 7 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 2009 VL 115 IS 10 BP 2111 EP 2118 DI 10.1002/cncr.24218 PG 8 WC Oncology SC Oncology GA 439HB UT WOS:000265617100014 PM 19280590 ER PT J AU Kyle, RA Jacobus, S Friedenberg, WR Slabber, CF Rajkumar, SV Greipp, PR AF Kyle, Robert A. Jacobus, Susanna Friedenberg, William R. Slabber, Coenraad Frederik Rajkumar, S. Vincent Greipp, Philip R. TI The Treatment of Multiple Myeloma Using Vincristine, Carmustine, Melphalan, Cyclophosphamide, and Prednisone (VBMCP) Alternating With High-dose Cyclophosphamide and alpha(2)beta Interferon Versus VBMCP SO CANCER LA English DT Article DE cyclophosphamide; interferon; myeloma; VBMCP ID COOPERATIVE-ONCOLOGY-GROUP; STEM-CELL TRANSPLANTATION; COMBINATION CHEMOTHERAPY; STANDARD CHEMOTHERAPY; RANDOMIZED-TRIALS AB BACKGROUND: A randomized controlled trial tested the hypothesis that aggressive initial therapy using high-dose cyclophosphamide (HiCy) and alpha(2)beta interferon (IFN) may be superior to standard combination alkylating agent regimens in the treatment of newly diagnosed myeloma. METHODS: This Eastern Cooperative Oncology Group trial evaluated 268 previously untreated patients with active multiple myeloma randomized to vincristine, carmustine, melphalan, cyclophosphamide, and prednisone (VBMCP) or VBMCP plus HiCy and recombinant IFN. RESULTS: The overall objective response was 62% in the VBMCP regimen and 68% in the VBMCP+HiCy+IFN group. The near complete response and complete response rates were 8.1% and 8.9%, respectively. Progression-free survival was 22.1 and 25.3 months, respectively. The median overall survival was 37.1 months for patients treated with VBMCP and 41.3 months for those treated with VBMCP+HiCY+IFN (P=.38). The 5-year overall survival rates were not significantly different between the 2 arms: 26.4% and 33%, respectively. Lethal toxicities occurred in 15 patients, including 10 from infection, but there was no significant difference in lethal toxicities between the 2 regimens. CONCLUSIONS: The study showed no significant benefit with the addition of HiCy and IFN to VBMCP. Cancer 2009;115:2155-64. (C) 2009 American Cancer Society. C1 [Kyle, Robert A.; Rajkumar, S. Vincent; Greipp, Philip R.] Mayo Clin, Div Hematol, Rochester, MN 55905 USA. [Jacobus, Susanna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Friedenberg, William R.] Guthrie Fdn Educ & Res, Dept Hematol, Sayre, PA USA. [Slabber, Coenraad Frederik] Univ Pretoria, Dept Med Oncol, ZA-0001 Pretoria, South Africa. RP Kyle, RA (reprint author), Mayo Clin, Div Hematol, Stabile 6-28 1st St SW, Rochester, MN 55905 USA. EM kyle.robert@mayo.edu FU NCI NIH HHS [CA13650, U10 CA066636, U24 CA114737, CA66636, U10 CA021115, U10 CA013650, U10 CA023318, CA23318, U10 CA059307-11, CA59307, CA21115] NR 27 TC 2 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 2009 VL 115 IS 10 BP 2155 EP 2164 DI 10.1002/cncr.24221 PG 10 WC Oncology SC Oncology GA 439HB UT WOS:000265617100019 PM 19248045 ER PT J AU Kaelin, WG AF Kaelin, William G., Jr. TI Treatment of Kidney Cancer Insights Provided by the VHL Tumor-Suppressor Protein SO CANCER LA English DT Article; Proceedings Paper CT 3rd International Conference on the Innovations and Challenges in Renal Cancer CY JUN 27-28, 2008 CL Cambridge, ENGLAND DE kidney cancer; von Hippel-Lindau disease; VHL tumor suppressor protein; hypoxia inducible factor ID RENAL-CELL-CARCINOMA; HYPOXIA-INDUCIBLE FACTOR; HIPPEL-LINDAU PROTEIN; PHASE-II TRIAL; VASCULAR TUMORS; PRIMARY CILIUM; IN-VIVO; CONDITIONAL INACTIVATION; TRANSACTIVATION DOMAINS; FACTOR (HIF)-1-ALPHA AB Germline inactivation of the VHL tumor suppressor gene is associated with an increased risk of clear cell carcinoma of the kidney in the context of von Hippel-Lindau (VHL) disease. Somatic VHL mutations are also common in nonhereditary (sporadic) clear cell carcinomas. The VHL protein (pVHL) has multiple functions that might be linked to tumor suppression, including targeting the hypoxia inducible factor (HIF) transcription factor for polyubiquitylation and proteasomal degradation. HIF, especially HIF2 alpha, appears to play a causal role in clear cell renal carcinogenesis based on genotype-phenotype correlations in VHL disease, laboratory experiments with human VHL-/- renal carcinoma cell lines, and genetically engineered mouse models. Deregulation of HIF almost certainly accounts for the high levels of vascular endothelial growth factor (VEGF) observed in kidney cancer and relates to their sensitivity to VEGF inhibitors. In addition, the beneficial effects of mammalian target of rapamycin (mTOR) inhibitors are likely due to, at least partly, their ability to down-regulate HIF pVHL, in a HIF-independent manner, also regulates a specialized structure called the primary cilium and regulates apoptosis via factors such as NF kappa B. Loss of the primary cilium probably facilitates the development of preneoplastic renal cysts, whereas increased NF kappa B might contribute to the resistance of kidney cancers to conventional cytotoxic agents. Cancer 2009;115(10 suppl):2262-72. (C) 2009 American Cancer Society. C1 [Kaelin, William G., Jr.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St,Mayer 457, Boston, MA 02115 USA. EM William_Kaelin@dfci.harvard.edu NR 110 TC 70 Z9 70 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 2009 VL 115 IS 10 BP 2262 EP 2272 DI 10.1002/cncr.24232 PG 11 WC Oncology SC Oncology GA 438YC UT WOS:000265591600003 PM 19402056 ER PT J AU Di Napoli, A Signoretti, S AF Di Napoli, Arianna Signoretti, Sabina TI Tissue Biomarkers in Renal Cell Carcinoma: Issues and Solutions SO CANCER LA English DT Article; Proceedings Paper CT 3rd International Conference on the Innovations and Challenges in Renal Cancer CY JUN 27-28, 2008 CL Cambridge, ENGLAND DE renal cell carcinoma; tissue biomarkers; disease prognosis; biomarker detection ID CARBONIC-ANHYDRASE-IX; KIDNEY CANCER; INDEPENDENT PREDICTOR; QUANTITATIVE-ANALYSIS; PROTEIN EXPRESSION; INTERFERON-ALPHA; BREAST-CANCER; IMMUNOHISTOCHEMISTRY; PROGNOSIS; SPECIMENS AB Renal cell carcinoma (RCC) is an aggressive malignancy that is associated with a high rate of metastasis. Although several promising therapeutic strategies are now available for the treatment of patients with metastatic kidney cancer, the prognosis of these patients remains poor. Research is ongoing to identify RCC-specific biomarkers that can improve early diagnosis, surveillance of tumor progression, and prediction of patient prognosis. The identification of biomarkers that may predict response to specific therapies also, will be useful in stratifying patients With RCC Tor treatment selection. Unfortunately I I biomarker detection and measurement in kidney tumor tissues can be biased significantly by the lack of standardization in tissue sample acquisition, storage, and analysis. Consequently, the establishment of standardize Operating procedures is necessary to maximize the accuracy of tissue-based biomarker assays. Herein, the authors discuss current issues in tissue-based translational research aimed at identifying clinically useful biomarkers for kidney cancer. Cancer 2009;115(10 suppl):2290-7. (C) 2009 American Cancer Society. C1 [Signoretti, Sabina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Signoretti, Sabina] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. RP Signoretti, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM ssignoretti@partners.org FU NCI NIH HHS [P50 CA101942] NR 44 TC 22 Z9 22 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 2009 VL 115 IS 10 BP 2290 EP 2297 DI 10.1002/cncr.24233 PG 8 WC Oncology SC Oncology GA 438YC UT WOS:000265591600006 PM 19402057 ER PT J AU McDermott, DF AF McDermott, David F. TI Immunotherapy of Metastatic Renal Cell Carcinoma SO CANCER LA English DT Article; Proceedings Paper CT 3rd International Conference on the Innovations and Challenges in Renal Cancer CY JUN 27-28, 2008 CL Cambridge, ENGLAND DE immunotherapy; renal cancer; interleukin-2; interferon-alpha; carbonic anhydrase IX ID DOSE RECOMBINANT INTERLEUKIN-2; PHASE-II TRIAL; ESTABLISHED PULMONARY METASTASES; RANDOMIZED CONTROLLED-TRIAL; AUTOLOGOUS DENDRITIC CELLS; CARBONIC-ANHYDRASE-IX; INTERFERON-ALPHA; SUBCUTANEOUS INTERLEUKIN-2; SPONTANEOUS REGRESSION; SOLID TUMORS AB Renal cell carcinoma (RCC) evokes an immune response, which occasionally has resulted in spontaneous and dramatic remissions. In an attempt to reproduce or accentuate this response, various immunotherapeutic strategies have been studied. The most consistent antitumor activity has been reported with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). In recent years, randomized trials have suggested that high-dose, intravenous bolus IL-2 is superior in terms of response rate and possibly in terms of response quality to regimens that involve either low-dose IL-2 and IFN-alpha, intermediate- or low-dose IL-2 alone, or low-dose IFN-alpha alone. More significantly, investigations associated with those trials suggested that the potential exists for identifying predictors of response (or resistance) and limiting IL-2 therapy to those patients who hare most likely to benefit. Although the role of low-dose, single-agent cytokines is limited, combinations of cytokines with targeted therapy may have merit. Several studies, including 2 completed, large, phase 3 trials of interferon plus bevacizumab versus interferon alone, have demonstrated superior efficacy with the combination regimen compared with cytokine monotherapy and suggested the potential of an additive effect that requires further exploration. For patients who are unlikely to benefit from IL-2 or who are unable to receive it, the emergence "targeted immunotherapy" offers hope for improved clinical outcome. Improvements in patient selection, novel agents, and combination therapy will be required to optimize the benefits of immunotherapy in metastatic RCC as the list of effective therapies grows. Cancer 2009;115(10 suppl):2298-305. (C) 2009 American Cancer Society. C1 [McDermott, David F.] Beth Israel Deaconess Med Ctr, Biol Therapy Program, Boston, MA 02215 USA. [McDermott, David F.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [McDermott, David F.] Renal Canc Program, Dana Farber Harvard Canc Ctr, Clin Res Subcomm, Boston, MA USA. RP McDermott, DF (reprint author), Beth Israel Deaconess Med Ctr, Biol Therapy Program, 375 Longwood Ave,MS-428, Boston, MA 02215 USA. EM dmcdermo@bidmc.harvard.edu FU NCI NIH HHS [P50 CA101942-01] NR 58 TC 67 Z9 71 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 2009 VL 115 IS 10 BP 2298 EP 2305 DI 10.1002/cncr.24236 PG 8 WC Oncology SC Oncology GA 438YC UT WOS:000265591600007 PM 19402060 ER PT J AU Atkins, MB Choueiri, TK Cho, D Regan, M Signoretti, S AF Atkins, Michael B. Choueiri, Toni K. Cho, Daniel Regan, Meredith Signoretti, Sabina TI Treatment Selection for Patients With Metastatic Renal Cell Carcinoma SO CANCER LA English DT Article; Proceedings Paper CT 3rd International Conference on the Innovations and Challenges in Renal Cancer CY JUN 27-28, 2008 CL Cambridge, ENGLAND DE renal cell carcinoma; immunotherapy; antiangiogenic therapy; target of rapamycin (TOR); inhibitors; treatment selection ID CARBONIC-ANHYDRASE-IX; PHASE-III TRIAL; INTERFERON-ALPHA; DOSE INTERLEUKIN-2; SUNITINIB; THERAPY; EXPRESSION; CANCER; TEMSIROLIMUS; PREDICTORS AB The availability of approved agents with distinct mechanisms of action has encouraged investigations to identify optimal treatment strategies for specific patients and specific tumor features. Study of tumors from patients treated with interleukin-2 (IL-2) has suggested that response was unlikely in patients with tumors with papillary features or low carbonic anhydrase IX (CAIX) expression. A model combining histologic features and CAIX expression separated patients into 2 groups of roughly equal size, with 96% of the responding patients being in the favorable prognostic group. Additional studies have begun to identify molecular features that might predict response to IL-2 therapy. In contrast, clinical trial data suggest that temsirolimus was relatively more active than interferon in patients with tumors containing non-clear cell features, Furthermore, pathologic examination showed no correlation of response with CAN expression, but an apparent association with high expression of either phospho-AKT or phospho-S6, proteins either upstream or downstream of mammalian target of rapamycin. Preliminary investigations of tumor specimens from patients receiving vascular endothelial growth factor-targeted therapy suggested that high hypoxia-inducible factor expression might predict response. In addition, response appeared more likely in tumors with mutated or methylated VHL genes; however, substantial antitumor activity was still observed in patients with VHL wild-type tumors, particularly in patients treated with either sunitinib or axitinib, rather than bevacizumab or sorafenib. Although these data provide some guidance in treatment selection, considerably more research is needed to identify and validate selection models for particular treatment approaches, and to enable rational and optimal utilization of the available treatment options. Cancer 2009;115(10 suppl):2327-33. (C) 2009 American Cancer Society. C1 [Atkins, Michael B.; Cho, Daniel] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02115 USA. [Atkins, Michael B.; Choueiri, Toni K.; Cho, Daniel; Regan, Meredith; Signoretti, Sabina] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Boston, MA USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Regan, Meredith] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Signoretti, Sabina] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Atkins, MB (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, MASCO Bldg,Room 412,375 Longwood Ave, Boston, MA 02115 USA. EM Matkins@bidmc.harvard.edu FU NCI NIH HHS [P50CA101942, P50 CA101942-05S1, P50 CA101942] NR 39 TC 23 Z9 26 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 2009 VL 115 IS 10 BP 2327 EP 2333 DI 10.1002/cncr.24231 PG 7 WC Oncology SC Oncology GA 438YC UT WOS:000265591600011 PM 19402069 ER PT J AU Volchenboum, SL Li, C Li, SL Attiyeh, EF Reynolds, CP Maris, JM Look, AT George, RE AF Volchenboum, Samuel L. Li, Cheng Li, Shuli Attiyeh, Edward F. Reynolds, C. Patrick Maris, John M. Look, A. Thomas George, Rani E. TI Comparison of Primary Neuroblastoma Tumors and Derivative Early-Passage Cell Lines Using Genome-Wide Single Nucleotide Polymorphism Array Analysis SO CANCER RESEARCH LA English DT Article ID PEDIATRIC-ONCOLOGY-GROUP; LOSS-OF-HETEROZYGOSITY; GENE AMPLIFICATION; SNP ARRAYS; CHROMOSOME; CLASSIFICATION; SUPPRESSOR; DELETIONS; DCHIPSNP; GAIN AB Stromal contamination is one of the major confounding factors in the analysis of solid tumor samples by single nucleotide polymorphism (SNP) arrays. As we propose to use genome-wide SNP microarray analysis as a diagnostic platform for neuroblastoma, the sensitivity, specificity, and accuracy of these studies must be optimized. To investigate the effects of stromal contamination, we derived early-passage cell lines from nine primary tumors and compared their genomic signature with that of the primary tumors using 100K SNP arrays. The average concordance between tumor and cell line for raw loss of heterozygosity (LOH) calls was 96% (range, 91-99%) and for raw copy number alterations, 71% (range, 43-87%). In general, there were a larger number of LOH events identified in the cell lines compared with the matched tumor samples (mean increase, 3.2% +/- 1.9%). We have developed an algorithm that shows that the presence of stroma contributes to under-reporting of LOH and copy number loss. Notable findings in this sample set were uniparental disomy of chromosome arms 11p, 1q, 14q, and 15q and a novel area of amplification on chromosome band 11p15. Our analysis shows that LOH was identified significantly more often in derived cell lines compared with the original tumor samples. Although these may in part be due to clonal selection during adaptation to tissue culture, our study indicates that stromal contamination may he it major contributing factor in underestimation of LOH and copy number loss events. [Cancer Res 2009;69(10):4143-9] C1 [Volchenboum, Samuel L.] Univ Chicago, Computat Inst, Chicago, IL 60637 USA. [Volchenboum, Samuel L.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Li, Cheng; Li, Shuli] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Look, A. Thomas; George, Rani E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Attiyeh, Edward F.; Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Oncol, Philadelphia, PA 19104 USA. [Reynolds, C. Patrick] Texas Tech Univ, Sch Med, Lubbock, TX 79409 USA. RP Volchenboum, SL (reprint author), Univ Chicago, Computat Inst, 5640 S Ellis RI405, Chicago, IL 60637 USA. EM slv@uchicago.edu OI Reynolds, C. Patrick/0000-0002-2827-8536 FU Children's Oncology Group Grant [U10 CA98543]; NIH [CA87847]; Bear Necessities Pediatric Cancer Foundation; Children's Oncology Group Young Investigator Award; Hope Street Kids Research Fellowship FX Grant support: Children's Oncology Group Grant U10 CA98543, NIH grant CA87847 (J.M. Maris). Bear Necessities Pediatric Cancer Foundation (S.L. Volchenboum). and Children's Oncology Group Young Investigator Award and the Hope Street Kids Research Fellowship (R.E. George). NR 27 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2009 VL 69 IS 10 BP 4143 EP 4149 DI 10.1158/0008-5472.CAN-08-3112 PG 7 WC Oncology SC Oncology GA 447TJ UT WOS:000266214400009 PM 19435921 ER PT J AU Szokalska, A Makowski, M Nowis, D Wilczynski, GM Kujawa, M Wojcik, C Mlynarczuk-Bialy, I Salwa, P Bil, J Janowska, S Agostinis, P Verfaillie, T Bugajski, M Gietka, J Issat, T Glodkowska, E Mrowka, P Stoklosa, T Hamblin, MR Mroz, P Jakobisiak, M Golab, J AF Szokalska, Angelika Makowski, Marcin Nowis, Dominika Wilczynski, Grzegorz M. Kujawa, Marek Wojcik, Cezary Mlynarczuk-Bialy, Izabela Salwa, Pawel Bil, Jacek Janowska, Sylwia Agostinis, Patrizia Verfaillie, Tom Bugajski, Marek Gietka, Jan Issat, Tadeusz Glodkowska, Eliza Mrowka, Piotr Stoklosa, Tomasz Hamblin, Michael R. Mroz, Pawel Jakobisiak, Marek Golab, Jakub TI Proteasome Inhibition Potentiates Antitumor Effects of Photodynamic Therapy in Mice through Induction of Endoplasmic Reticulum Stress and Unfolded Protein Response SO CANCER RESEARCH LA English DT Article ID SINGLET OXYGEN; OXIDATIVE STRESS; CELL-DEATH; DEGRADATION; PHOTOSENSITIZATION; CARBONYLATION; INACTIVATION; PHOTODAMAGE; DISEASE; BCL-2 AB Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity toward tumor cells by inducing production of reactive oxygen species such as singlet oxygen. PDT leads to oxidative damage of cellular macromolecules, including proteins that undergo multiple modifications such as fragmentation, cross-linking, and carbonylation that result in protein unfolding and aggregation. Because the major mechanism for elimination of carbonylated proteins is their degradation by proteasomes, we hypothesized that a combination of PDT with proteasome inhibitors might lead to accumulation of carbonylated proteins in endoplasmic reticulum (ER), aggravated ER stress, and potentiated cytotoxicity toward tumor cells. We observed that Photofrin-mediated PDT leads to robust carbonylation of cellular proteins and induction of unfolded protein response. Pretreatment of tumor cells with three different proteasome inhibitors, including bortezomib, MG132, and PSI, gave increased accumulation of carbonylated and ubiquitinated proteins in PDT-treated cells. Proteasome inhibitors effectively sensitized tumor cells of murine (EMT6 and C-26) as well as human (HeLa) origin to PDT-mediated cytotoxicity. Significant retardation of tumor growth with 60% to 100% complete responses was observed in vivo in two different murine tumor models (EMT6 and C-26) when PDT was combined with either bortezomib or PSI. Altogether, these observations indicate that combination of PDT with proteasome inhibitors leads to potentiated antitumor effects. The results of these studies are of immediate clinical application because bortezomib is a clinically approved drug that undergoes extensive clinical evaluations for the treatment of solid tumors. [Cancer Res 2009;69(10):4235-43] C1 [Szokalska, Angelika; Makowski, Marcin; Nowis, Dominika; Salwa, Pawel; Bil, Jacek; Janowska, Sylwia; Bugajski, Marek; Gietka, Jan; Issat, Tadeusz; Glodkowska, Eliza; Mrowka, Piotr; Stoklosa, Tomasz; Jakobisiak, Marek; Golab, Jakub] Med Univ Warsaw, Ctr Biostruct Res, Dept Immunol, PL-02097 Warsaw, Poland. [Wilczynski, Grzegorz M.; Kujawa, Marek; Mlynarczuk-Bialy, Izabela] Med Univ Warsaw, Ctr Biostruct Res, Dept Histol & Embryol, PL-02097 Warsaw, Poland. [Wilczynski, Grzegorz M.] M Nencki Inst Expt Biol, Lab Mol & Syst Neuromorphol, PL-02093 Warsaw, Poland. [Wojcik, Cezary] Indiana Univ, Dept Anat & Cell Biol, Sch Med, Evansville, IN USA. [Agostinis, Patrizia; Verfaillie, Tom] Catholic Univ Louvain, Dept Mol & Cell Biol, B-3000 Louvain, Belgium. [Hamblin, Michael R.; Mroz, Pawel] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.; Mroz, Pawel] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Golab, J (reprint author), Med Univ Warsaw, Ctr Biostruct Res, Dept Immunol, 1A Banacha St,F Bldg, PL-02097 Warsaw, Poland. EM jakub.golab@wum.edu.pl RI Muchowicz, Angelika/J-7494-2012; Golab, Jakub/K-6974-2013; OI Golab, Jakub/0000-0002-2830-5100; Nowis, Dominika/0000-0003-2748-9523; Bil, Jacek/0000-0002-8724-5611; Stoklosa, Tomasz/0000-0001-6918-5056; Hamblin, Michael/0000-0001-6431-4605 FU Ministry of Science and Higher Education-Poland [N40112331/2736, R0504303, N401324033]; Medical University of Warsaw [1M19/N, 1M19/WB1/07, 1M19/WB2/07]; Fonds voor Wetenschappelijk Onderzoek [G.0492.05]; NIH [R01-CA/AI838801]; American Cancer Society [IRG-84-002-22]; Foundation for Polish Science. FX Grant support: Ministry of Science and Higher Education-Poland grants N40112331/2736, R0504303 (J. Golab), and N401324033 (D. Nowis); Medical University of Warsaw grants 1M19/N (M. Jakobisiak), 1M19/WB1/07 (M. Jakobisiak), 1M19/WB2/07 (D. Nowis), and 1M19/NM2/07 (P. Salwa); K.U.Leuven grant OT/06/49 (P. Agostinis); "Fonds voor Wetenschappelijk Onderzoek" (FWO)-Vlanderen grant G.0492.05 (P. Agostinis); U.S. NIH grant R01-CA/AI838801 (M.R. Hamblin and P. Mroz); and an institutional appropriation of the American Cancer Society grant IRG-84-002-22 (C. Wojcik). T. Issat is a recipient of the START stipend from the Foundation for Polish Science. NR 48 TC 51 Z9 54 U1 2 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2009 VL 69 IS 10 BP 4235 EP 4243 DI 10.1158/0008-5472.CAN-08-3439 PG 9 WC Oncology SC Oncology GA 447TJ UT WOS:000266214400020 PM 19435917 ER PT J AU Wright, SM Woo, YH Alley, TL Shirley, BJ Akeson, EC Snow, KJ Maas, SA Elwell, RL Foreman, O Mills, KD AF Wright, Sarah M. Woo, Yong H. Alley, Travis L. Shirley, Bobbi-Jo Akeson, Ellen C. Snow, Kathy J. Maas, Sarah A. Elwell, Rachel L. Foreman, Oded Mills, Kevin D. TI Complex Oncogenic Translocations with Gene Amplification Are Initiated by Specific DNA Breaks in Lymphocytes SO CANCER RESEARCH LA English DT Article ID V(D)J RECOMBINATION; GENOMIC INSTABILITY; B-CELLS; ARTEMIS; CLEAVAGE; END; DEFICIENT; REPAIR; MICE; P53 AB Chromosomal instability is a hallmark of many tumor types. Complex chromosomal rearrangements with associated gene amplification, known as complicons, characterize many hematologic and solid cancers. Whereas chromosomal aberrations, including complicons, are useful diagnostic and prognostic cancer markers, their molecular origins are not known. Although accumulating evidence has implicated DNA double-strand break repair in suppression of oncogenic genome instability, the genomic elements required for chromosome rearrangements, especially complex lesions, have not been elucidated. Using a mouse model of B-lineage lymphoma, characterized by complicon formation involving the immunoglobulin heavy chain (Igh) locus and the c-myc oncogene, we have now investigated the requirement for specific genomic segments as donors for complex rearrangements. We now show that specific DNA double-strand breaks, occurring within a narrow segment of Igh, are necessary to initiate complicon formation. By contrast, neither specific DNA breaks nor the powerful intronic enhancer E mu are required for complicon-independent oncogenesis. This study is the first to delineate mechanisms of complex versus simple instability and the first to identify specific chromosomal elements required for complex chromosomal aberrations. These findings will illuminate genomic cancer susceptibility and risk factors. [Cancer Res 2009;69(10):4454-60] C1 [Woo, Yong H.; Alley, Travis L.; Shirley, Bobbi-Jo; Akeson, Ellen C.; Snow, Kathy J.; Elwell, Rachel L.; Foreman, Oded; Mills, Kevin D.] Jackson Lab, Bar Harbor, ME 04609 USA. [Wright, Sarah M.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Maas, Sarah A.] Mt Desert Isl Biol Lab, Salsbury Cove, ME USA. RP Mills, KD (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM Sarah.Wright@joslin.harvard.edu; smaas@mdibl.org; Kevin.mills@jax.org FU NIH/National Cancer Institute [5R01 CA 115665-03]; NIH/National Center for Research Resources [2P20RR018789-06]; National Science Foundation Integrative Graduate Education and Research Training Grant (University of Maine) [0221625] FX NIH/National Cancer Institute grant 5R01 CA 115665-03 (K.D. Mills. Principal Investigator) and partial support by NIH/National Center for Research Resources grant 2P20RR018789-06 (Project 4, K.D.M. Maine Medical Center Research Institute. Wojchowski, Principal Investigator). Y.H. Woo and K.J. Snow were supported by National Science Foundation Integrative Graduate Education and Research Training Grant 0221625 (University of Maine). NR 34 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2009 VL 69 IS 10 BP 4454 EP 4460 DI 10.1158/0008-5472.CAN-08-4515 PG 7 WC Oncology SC Oncology GA 447TJ UT WOS:000266214400045 PM 19435904 ER PT J AU North, TE Goessling, W Peeters, M Li, PL Ceol, C Lord, AM Weber, GJ Harris, J Cutting, CC Huang, P Dzierzak, E Zon, LI AF North, Trista E. Goessling, Wolfram Peeters, Marian Li, Pulin Ceol, Craig Lord, Allegra M. Weber, Gerhard J. Harris, James Cutting, Claire C. Huang, Paul Dzierzak, Elaine Zon, Leonard I. TI Hematopoietic Stem Cell Development Is Dependent on Blood Flow SO CELL LA English DT Article ID NITRIC-OXIDE SYNTHASE; EMBRYONIC VASCULAR DEVELOPMENT; YOLK-SAC; MOUSE EMBRYO; PROGENITOR CELLS; BETA-CATENIN; ZEBRAFISH; EXPRESSION; GENE; DISRUPTION AB During vertebrate embryogenesis, hematopoietic stem cells (HSCs) arise in the aorta-gonads-mesonephros (AGM) region. We report here that blood flow is a conserved regulator of HSC formation. In zebrafish, chemical blood flow modulators regulated HSC development, and silent heart (sih) embryos, lacking a heartbeat and blood circulation, exhibited severely reduced HSCs. Flow-modifying compounds primarily affected HSC induction after the onset of heartbeat; however, nitric oxide (NO) donors regulated HSC number even when treatment occurred before the initiation of circulation, and rescued HSCs in sih mutants. Morpholino knockdown of nos1 (nnos/enos) blocked HSC development, and its requirement was shown to be cell autonomous. In the mouse, Nos3 (eNos) was expressed in HSCs in the AGM. Intrauterine Nos inhibition or embryonic Nos3 deficiency resulted in a reduction of hematopoietic clusters and transplantable murine HSCs. This work links blood flow to AGM hematopoiesis and identifies NO as a conserved downstream regulator of HSC development. C1 [North, Trista E.; Goessling, Wolfram; Li, Pulin; Ceol, Craig; Lord, Allegra M.; Weber, Gerhard J.; Zon, Leonard I.] Harvard Univ, Sch Med, Stem Cell Program & Hematol Oncol, Childrens Hosp,Howard Hughes Med Inst,Harvard Ste, Boston, MA 02115 USA. [North, Trista E.; Harris, James] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. [Goessling, Wolfram; Cutting, Claire C.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Goessling, Wolfram] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Goessling, Wolfram] Dana Farber Canc Inst, Boston, MA 02115 USA. [Peeters, Marian; Dzierzak, Elaine] Erasmus MC, Erasmus Stem Cell Inst, NL-3000 DR Rotterdam, Netherlands. [Huang, Paul] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Zon, LI (reprint author), Harvard Univ, Sch Med, Stem Cell Program & Hematol Oncol, Childrens Hosp,Howard Hughes Med Inst,Harvard Ste, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu OI Goessling, Wolfram/0000-0001-9972-1569 FU National Institutes of Health; Netherlands Besluit Subsidies Investeringen Kennisinfrastructuur; Howard Hughes Medical Institute investigator FX We thank M. Lin and J. Loscalzo for helpful suggestions, D. Atochin for assistance with Nos knockout mice, and W. Davis for technical support with spinning- disk confocal microscopy. We thank K. R. Kopani, J. Ojeda, and A. Meyers for technical assistance with the zebrafish HSC screen. This work was supported by the National Institutes of Health (T. E. N., W. G., E. D., and L. I. Z) and a Netherlands Besluit Subsidies Investeringen Kennisinfrastructuur award (E. D.). L. I. Z. is a Howard Hughes Medical Institute investigator. NR 51 TC 215 Z9 222 U1 2 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAY 15 PY 2009 VL 137 IS 4 BP 736 EP 748 DI 10.1016/j.cell.2009.04.023 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 446IA UT WOS:000266114100021 PM 19450519 ER PT J AU Ahn, J Poyurovsky, MV Baptiste, N Beckerman, R Cain, C Mattia, M McKinney, K Zhou, JM Zupnick, A Gottifredi, V Prives, C AF Ahn, Jinwoo Poyurovsky, Masha V. Baptiste, Nicole Beckerman, Rachel Cain, Christine Mattia, Melissa McKinney, Kristine Zhou, Jianmin Zupnick, Andrew Gottifredi, Vanesa Prives, Carol TI Dissection of the sequence-specific DNA binding and exonuclease activities reveals a superactive yet apoptotically impaired mutant p53 protein SO CELL CYCLE LA English DT Article DE p53; apoptosis; exonuclease activity; DNA binding; transcription; cell cycle ID C-TERMINAL DOMAIN; CELL-CYCLE CHECKPOINT; REPAIR ENZYME HAP1; CRYSTAL-STRUCTURE; EXCISION-REPAIR; WILD-TYPE; FUNCTIONAL INTERACTION; HOLLIDAY JUNCTIONS; TUMOR-CELLS; CORE DOMAIN AB Both sequence-specific DNA binding and exonuclease activities have been mapped to the central conserved core domain of p53. To gain more information about these two activities a series of mutants were generated that changed core domain histidine residues. Of these mutants, only one, H115N p53, showed markedly reduced exonuclease activity (ca. 15% of wild-type). Surprisingly, purified H115N p53 protein was found to be significantly more potent than wild-type p53 in binding to DNA by several criteria including gel mobility shift assay, filter binding and DNase I footprinting. Interestingly as well, non-specific DNA binding by the core domain of H115N p53 is superior to that of wild-type p53. To study H115N p53 in vivo, clones of H1299 cells expressing tetracycline regulated wild-type or H115N p53 were generated. H115N was both more potent than wild-type p53 in inducing p53 target genes such as p21 and PIG3 and was also more effective in arresting cells in G(1). Unexpectedly, in contrast to wild-type p53, H115N p53 was markedly impaired in causing apoptosis when cells were subjected to DNA damage. Our results indicate that the exonuclease activity and transcriptional activation functions of p53 can be separated. They also extend previous findings showing that cell cycle arrest and apoptosis are separable functions of p53. Finally, these experiments confirm that DNA binding and exonuclease activities are distinct features of the p53 core domain. C1 [Poyurovsky, Masha V.; Baptiste, Nicole; Beckerman, Rachel; Cain, Christine; Zhou, Jianmin; Zupnick, Andrew; Prives, Carol] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. [Ahn, Jinwoo] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA USA. [Mattia, Melissa] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. [McKinney, Kristine] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gottifredi, Vanesa] Univ Buenos Aires, CONICET, Fdn Inst Leloir, Cell Cycle & Genom Stabil Lab, Buenos Aires, DF, Argentina. RP Prives, C (reprint author), Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. EM clp3@columbia.edu OI Gottifredi, Vanesa/0000-0001-9656-5951 FU NIH [CA77742] FX We are grateful to Ella Freulich for expert technical assistance. This work was supported by NIH grant CA77742. NR 74 TC 12 Z9 12 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY 15 PY 2009 VL 8 IS 10 BP 1603 EP 1615 PG 13 WC Cell Biology SC Cell Biology GA 446IP UT WOS:000266115600028 PM 19462533 ER PT J AU Anand, S Honari, G Hasan, T Elson, P Maytin, EV AF Anand, Sanjay Honari, Golara Hasan, Tayyaba Elson, Paul Maytin, Edward V. TI Low-Dose Methotrexate Enhances Aminolevulinate-Based Photodynamic Therapy in Skin Carcinoma Cells In vitro and In vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID INDUCED PROTOPORPHYRIN-IX; PROSTATE-CANCER CELLS; ACUTE PROMYELOCYTIC LEUKEMIA; ACID-INDUCED PROTOPORPHYRIN; TRANS-RETINOIC ACID; 5-AMINOLEVULINIC ACID; EPIDERMAL-KERATINOCYTES; TOPICAL APPLICATION; FUNCTIONAL-ANALYSIS; DIFFERENTIATION AB Purpose: To improve treatment efficacy and tumor cell selectivity of delta-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) via pretreatment of cells and tumors with methotrexate to enhance intracellular photosensitizer levels. Experimental Design: Skin carcinoma cells, in vitro and in vivo, served as the model system. Cultured human SCC13 and HEK1 cells, normal keratinocytes, and in vivo skin tumor models were preconditioned with methotrexate for 72 h and then incubated with ALA for 4 h. Changes in protoporphyrin IX (PpIX) levels and cell survival after light exposure were assessed. Results: Methotrexate preconditioning of monolayer cultures preferentially increased intracellular PpIX levels 2- to 4-fold in carcinoma cells versus normal keratinocytes. Photodynamic killing was synergistically enhanced by the combined therapy compared with PDT alone. Methotrexate enhancement of PpIX levels was achieved over a broad methotrexate concentration range (0.0003-1.0 mg/L; 0.6 nmol/L-2 mmol/L). PpIX enhancement correlated with changes in protein expression of key porphyrin pathway enzymes, similar to 4-fold increase in coproporphyrinogen oxidase and stable or slightly decreased expression of ferrochelatase. Differentiation markers (E-cadherin, involucrin, and filaggrin) were also selectively induced by methotrexate in carcinoma cells. In vivo relevance was established by showing that methotrexate preconditioning enhances PpIX accumulation in three models: (a) organotypic cultures of immortalized keratinocytes, (b) chemically induced skin tumors in mice; and (c) human A431 squamous cell tumors implanted subcutaneously in mice. Conclusion: Combination therapy using short-term exposure to low-dose methotrexate followed by ALA-PDT should be further investigated as a new combination modality to enhance efficacy and selectivity of PDT for epithelial carcinomas. C1 [Anand, Sanjay; Maytin, Edward V.] Cleveland Clin, Dept Biomed Engn, Lerner Res Inst, Cleveland, OH 44195 USA. [Honari, Golara; Maytin, Edward V.] Cleveland Clin, Dept Dermatol, Lerner Res Inst, Cleveland, OH 44195 USA. [Elson, Paul] Cleveland Clin, Dept Quantitat Hlth Sci, Lerner Res Inst, Cleveland, OH 44195 USA. [Hasan, Tayyaba; Maytin, Edward V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Maytin, EV (reprint author), Cleveland Clin, Dept Biomed Engn, Lerner Res Inst, Mailstop ND-20,9500 Euclid Ave, Cleveland, OH 44195 USA. EM maytine@ccf.org FU NIH [CA84203] FX Grant support: NIH grant CA84203. NR 53 TC 64 Z9 64 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2009 VL 15 IS 10 BP 3333 EP 3343 DI 10.1158/1078-0432.CCR-08-3054 PG 11 WC Oncology SC Oncology GA 448SP UT WOS:000266282600012 PM 19447864 ER PT J AU Naumov, GN Nilsson, MB Cascone, T Briggs, A Straume, O Akslen, LA Lifshits, E Byers, LA Xu, L Wu, HK Janne, P Kobayashi, S Halmos, B Tenen, D Tang, XM Engelman, J Yeap, B Folkman, J Johnson, BE Heymach, JV AF Naumov, George N. Nilsson, Monique B. Cascone, Tina Briggs, Alexandra Straume, Oddbjorn Akslen, Lars A. Lifshits, Eugene Byers, Lauren Averett Xu, Li Wu, Hua-Kang Janne, Pasi Kobayashi, Susumu Halmos, Balazs Tenen, Daniel Tang, Xi M. Engelman, Jeffrey Yeap, Beow Folkman, Judah Johnson, Bruce E. Heymach, John V. TI Combined Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor (EGFR) Blockade Inhibits Tumor Growth in Xenograft Models of EGFR Inhibitor Resistance SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; HUMAN PANCREATIC-CARCINOMA; ACQUIRED-RESISTANCE; PHASE-II; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; GEFITINIB; MUTATIONS; THERAPY AB Purpose: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) gefitinib and erlotinib benefit some non-small cell lung cancer (NSCLC) patients, but most do not respond (primary resistance) and those who initially respond eventually progress (acquired resistance). EGFR TKI resistance is not completely understood and has been associated with certain EGFR and K-RAS mutations and MET amplification. Experimental Design: We hypothesized that dual inhibition of the vascular endothelial growth factor (VEGF) and EGFR pathways may overcome primary and acquired resistance. We investigated the VEGF receptor/EGFR TKI vandetanib, and the combination of bevacizumab and erlotinib in vivo using xenograft models of EGFR TKI sensitivity, primary resistance, and three models of acquired resistance, including models with mutated K-RAS and secondary EGFR T790M mutation. Results: Vandetanib, gefitinib, and erlotinib had similar profiles of in vitro activity and caused sustained tumor regressions in vivo in the sensitive HCC827 model. In all four resistant models, vandetanib and bevacizumab/erlotinib were significantly more effective than erlotinib or gefitinib alone. Erlotinib resistance was associated with a rise in both host and tumor-derived VEGF but not EGFR secondary mutations in the KRAS mutant-bearing A549 xenografts. Dual inhibition reduced tumor endothelial proliferation compared with VEGF or EGFR blockade alone, suggesting that the enhanced activity of dual inhibition is due at least in part to antiendothelial effects. Conclusion: These studies suggest that erlotinib resistance may be associated with a rise in both tumor cell and host stromal VEGF and that combined blockade of the VEGFR and EGFR pathways can abrogate primary or acquired resistance to EGFR TKIs. This approach merits further evaluation in NSCLC patients. C1 [Heymach, John V.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Oncol, Unit 432, Houston, TX 77030 USA. [Naumov, George N.; Briggs, Alexandra; Straume, Oddbjorn; Lifshits, Eugene; Folkman, Judah; Heymach, John V.] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Janne, Pasi; Yeap, Beow; Johnson, Bruce E.; Heymach, John V.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Kobayashi, Susumu; Halmos, Balazs; Tenen, Daniel] Harvard Univ, Div Hematol Oncol, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Engelman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Straume, Oddbjorn; Akslen, Lars A.] Univ Bergen, Sect Pathol, Gade Inst, N-5020 Bergen, Norway. [Straume, Oddbjorn] Univ Bergen, Sect Oncol, Inst Internal Med, N-5020 Bergen, Norway. RP Heymach, JV (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Oncol, Unit 432, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jheymach@mdanderson.org RI Akslen, Lars /C-1202-2017; Straume, Oddbjorn/C-2186-2017; OI Akslen, Lars /0000-0003-2710-9543; Straume, Oddbjorn/0000-0001-8867-3645; Tenen, Daniel/0000-0002-6423-3888 FU DFCI Lung SPORE NIH [P20 CA090578]; University of Texas Southwestern Medical Center; Anderson Cancer Center SPORE NIH [P50 CA070907]; HHMI-SPORE Pilot Research Project; Damon Runyon Cancer Research Foundation [Cl 24-04]; Physician Scientist Program FX This work was supported by DFCI Lung SPORE NIH grant P20 CA090578, the University of Texas Southwestern Medical Center and M. D. Anderson Cancer Center SPORE NIH grant P50 CA070907, and HHMI-SPORE Pilot Research Project grant. J.V. Heymach is a Damon Runyon-Lilly Clinical Investigator supported in part by the Damon Runyon Cancer Research Foundation (Cl 24-04), and the Physician Scientist Program at M. D. Anderson. 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 44 TC 126 Z9 133 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2009 VL 15 IS 10 BP 3484 EP 3494 DI 10.1158/1078-0432.CCR-08-2904 PG 11 WC Oncology SC Oncology GA 448SP UT WOS:000266282600027 PM 19447865 ER PT J AU Baar, J Silverman, P Lyons, J Fu, PF Abdul-Karim, F Ziats, N Wasman, J Hartman, P Jesberger, J Dumadag, L Hohler, E Leeming, R Shenk, R Chen, H McCrae, K Dowlati, A Remick, SC Overmoyer, B AF Baar, Joseph Silverman, Paula Lyons, Janice Fu, Pingfu Abdul-Karim, Fadi Ziats, Nicholas Wasman, Jay Hartman, Paul Jesberger, John Dumadag, Leda Hohler, Erin Leeming, Rosemary Shenk, Robert Chen, Helen McCrae, Keith Dowlati, Afshin Remick, Scot C. Overmoyer, Beth TI A Vasculature-Targeting Regimen of Preoperative Docetaxel with or without Bevacizumab for Locally Advanced Breast Cancer: Impact on Angiogenic Biomarkers SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; CELL-ADHESION MOLECULE-1; PHASE-II TRIAL; E-SELECTIN; NEOADJUVANT CHEMOTHERAPY; TUMOR ANGIOGENESIS; RECEPTORS; CARCINOMA; REGRESSION; ICAM-1 AB Purpose: Taxanes have effects on angiogenesis causing difficulties in separating biological effects of chemotherapy from those due to angiogenesis inhibitors. This randomized phase 11 trial was designed to evaluate the additional biomarker effect on angiogenesis when bevacizumab is added to docetaxel. Experimental Design: Patients with inoperable breast cancer were randomized to either 2 cycles of preoperative docetaxel (D) 35 mg/m(2) i.v. weekly for 6 weeks, followed by a 2-week break; or docetaxel with bevacizumab 10 mg/kg i.v. every other week for a total of 16 weeks (DB). Plasma and serum markers of endothelial damage, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and tumor microvessel density were assessed before treatment and at the end of each preoperative cycle. Results: Forty-nine patients were randomized (DB, 24; D, 25). There was no difference in overall clinical response, progression-free survival, or overall survival. Vascular endothelial growth factor increased during treatment; more so with DB (P < 0.0001). Vascular cell adhesion molecule-1 (VCAM-1) also increased (P < 0.0001); more so with DB (P = 0.069). Intercellular adhesion molecule increased (P = 0.018) and E-selectin decreased (P = 0.006) overall. Baseline levels of VCAM-1 and E-selectin correlated with clinical response by univariate analysis. DCE-MRI showed a greater decrease in tumor perfusion calculated by initial area under the curve for the first 90 seconds in DB (P = 0.024). DCE-MRI also showed an overall decrease in tumor volume (P = 0.012). Conclusion: Bevacizumab plus docetaxel caused a greater increase in vascular endothelial growth factor and VCAM-1, and a greater reduction in tumor perfusion by DCE-MRI compared with docetaxel. Clinical outcomes of inoperable breast cancer were predicted by changes in VCAM-1 and E-selectin. C1 [Overmoyer, Beth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Baar, Joseph; Silverman, Paula; Lyons, Janice; Fu, Pingfu; Abdul-Karim, Fadi; Ziats, Nicholas; Wasman, Jay; Hartman, Paul; Jesberger, John; Dumadag, Leda; Hohler, Erin; Leeming, Rosemary; Shenk, Robert; McCrae, Keith; Dowlati, Afshin] Univ Hosp Case Med Ctr, Dev Therapeut Program, Cleveland, OH USA. [Hartman, Paul; Hohler, Erin] Univ Hosp Case Med Ctr, Case Comprehens Canc Ctr, Cleveland, OH USA. [Baar, Joseph; Silverman, Paula; McCrae, Keith; Dowlati, Afshin] Univ Hosp Case Med Ctr, Dept Med, Cleveland, OH USA. [Lyons, Janice] Univ Hosp Case Med Ctr, Dept Radiat Oncol, Cleveland, OH USA. [Fu, Pingfu] Univ Hosp Case Med Ctr, Dept Biostat & Epidemiol, Cleveland, OH USA. [Abdul-Karim, Fadi; Ziats, Nicholas; Wasman, Jay] Univ Hosp Case Med Ctr, Dept Pathol, Cleveland, OH USA. [Jesberger, John] Univ Hosp Case Med Ctr, Dept Radiol, Cleveland, OH USA. [Leeming, Rosemary; Shenk, Robert] Univ Hosp Case Med Ctr, Dept Surg, Cleveland, OH USA. [Chen, Helen] NCI, Bethesda, MD 20892 USA. [Remick, Scot C.] W Virginia Univ, Sch Med, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. RP Overmoyer, B (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM Beth_Overmoyer@DFCI.HARVARD.EDU FU NIH [K23 CA87725, P30 CA43703]; Avon Supplement [P30 C143703, U01 CA62502]; National Cancer Institute Translational Research Initiative [M01 RR00080]; Sanofi Aventis FX NIH grants: K23 CA87725 (B. Overmoyer); P30 CA43703, Avon Supplement to P30 C143703 (B. Overmoyer), U01 CA62502 and National Cancer Institute Translational Research Initiative; M01 RR00080; Sanofi Aventis. NR 46 TC 64 Z9 68 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2009 VL 15 IS 10 BP 3583 EP 3590 DI 10.1158/1078-0432.CCR-08-2917 PG 8 WC Oncology SC Oncology GA 448SP UT WOS:000266282600038 PM 19417018 ER PT J AU Hanrahan, EO Ryan, AJ Mann, H Kennedy, SJ Langmuir, P Natale, RB Herbst, RS Johnson, BE Heymach, JV AF Hanrahan, Emer O. Ryan, Anderson J. Mann, Helen Kennedy, Sarah J. Langmuir, Peter Natale, Ronald B. Herbst, Roy S. Johnson, Bruce E. Heymach, John V. TI Baseline Vascular Endothelial Growth Factor Concentration as a Potential Predictive Marker of Benefit from Vandetanib in Non-Small Cell Lung Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID TYROSINE KINASE INHIBITORS; ADVANCED COLORECTAL-CANCER; PHASE-III TRIAL; FACTOR RECEPTOR; BREAST-CANCER; THERAPEUTIC IMPLICATIONS; TUMOR ANGIOGENESIS; IN-VIVO; BEVACIZUMAB; PACLITAXEL AB Purpose: Vandetanib [vascular endothelial growth factor (VEGF) receptor/epidermal growth factor receptor/RET inhibitor] has shown improvements in progression-free survival (PFS) in advanced non-small cell lung cancer in three randomized phase II studies: vandetanib versus gefitinib (study 3), docetaxel vandetanib (study 6), and carboplatin-paclitaxel and/or vandetanib (study 7). In study 7, vandetanib monotherapy was inferior to carboplatin-paclitaxel. We performed an exploratory retrospective analysis of the relationship between baseline circulating VEGF concentrations and PFS. Experimental Design: Mean baseline VEGF levels were determined by ELISA from two baseline samples of plasma (163 of 168 patients, study 3; 65 of 127, study 6) or serum (144 of 181, study 7). High baseline VEGF values were above the immunoassay reference range for healthy subjects; low baseline VEGF values were within the range. Results: Patients with low baseline VEGF had a lower risk of disease progression with vandetanib versus gefitinib [hazard ratio (HR), 0.55; 95% confidence interval (95% CI), 0.35-0.86; P = 0.01] or vandetanib 100 mg/d + docetaxel versus docetaxel (HR, 0.25; 95% CI, 0.09-0.68; P = 0.01). High VEGF patients had a similar risk of disease progression with vandetanib monotherapy versus gefitinib (HR, 1.03; 95% CI, 0.60-1.75; P = 0.92) or vandetanib 100 mg/d + docetaxel versus docetaxel (HR, 0.95; 95% CI, 0.25-3.61; P = 0.94). In study 7, low VEGF patients had a similar risk of disease progression with vandetanib monotherapy 300 mg/d versus carboplatin-paclitaxel (HR, 0.80; 95% CI, 0.41-1.56; P = 0.51); high VEGF patients progressed more quickly (HR, 1.60; 95% CI, 0.81-3.15; P = 0.17). Conclusions: These analyses suggest that low baseline circulating VEGF may be predictive of PFS advantage in patients with advanced non-small cell lung cancer receiving vandetanib versus gefitinib or vandetanib + docetaxel versus docetaxel. Moreover, patients with low VEGF levels may have a similar outcome with either vandetanib monotherapy or carboplatin-paclitaxel. C1 [Heymach, John V.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol & Canc Biol, Unit 432, Houston, TX 77030 USA. [Ryan, Anderson J.; Mann, Helen; Kennedy, Sarah J.] AstraZeneca, Macclesfield, Cheshire, England. [Langmuir, Peter] AstraZeneca, Wilmington, DE USA. [Natale, Ronald B.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Heymach, JV (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol & Canc Biol, Unit 432, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jheymach@mdanderson.org RI Ryan, Anderson/O-7701-2015 OI Ryan, Anderson/0000-0001-6241-7969 FU Damon Runyan Cancer Research Foundation [CI 24-04]; American Society for Clinical Oncology Career Development Award; American Society for Clinical Oncology Young Investigator Award; AstraZeneca FX Damon Runyan Cancer Research Foundation grant CI 24-04 and American Society for Clinical Oncology Career Development Award (J.V. Heymach) and American Society for Clinical Oncology Young Investigator Award (E.O. Hanrahan). This study, including the editorial assistance provided by John Matthew (Muclskipper Bioscience), was supported financially by AstraZeneca. NR 42 TC 69 Z9 74 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2009 VL 15 IS 10 BP 3600 EP 3609 DI 10.1158/1078-0432.CCR-08-2568 PG 10 WC Oncology SC Oncology GA 448SP UT WOS:000266282600040 PM 19447868 ER PT J AU McDonald, JR Zeringue, AL Caplan, L Ranganathan, P Xian, H Burroughs, TE Fraser, VJ Cunningham, F Eisen, SA AF McDonald, Jay R. Zeringue, Angelique L. Caplan, Liron Ranganathan, Prabha Xian, Hong Burroughs, Thomas E. Fraser, Victoria J. Cunningham, Fran Eisen, Seth A. TI Herpes Zoster Risk Factors in a National Cohort of Veterans with Rheumatoid Arthritis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ADVERSE DRUG-REACTIONS; ADMINISTRATIVE DATA; UNITED-STATES; INFECTION; GUIDELINES; MANAGEMENT; AGREEMENT; ACCURACY; UPDATE; AGENTS AB Background. Herpes zoster occurs more commonly in patients taking immunosuppressive medications, although the risk associated with different medications is poorly understood. Methods. We conducted a retrospective cohort study involving 20,357 patients who were followed in the Veterans Affairs healthcare system and treated for rheumatoid arthritis from October 1998 through June 2005. Cox proportional hazards regression was used to determine risk factors for herpes zoster and herpes zoster-free survival. Chart review was performed to validate the diagnosis of herpes zoster. Results. The incidence of herpes zoster was 9.96 episodes per 1000 patient-years. In time-to-event analysis, patients receiving medications used to treat mild rheumatoid arthritis were less likely to have an episode of herpes zoster than patients receiving medications used to treat moderate and severe rheumatoid arthritis (P < .001). Independent risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, malignancy, chronic lung disease, renal failure, and liver disease. Among patients receiving tumor necrosis factor-alpha antagonists, etanercept (hazard ratio, 0.62) and adalimumab (hazard ratio, 0.53) were associated with a lower risk of herpes zoster. There was excellent agreement between the International Classification of Diseases, Version 9, Clinical Modification diagnosis of herpes zoster and diagnosis by chart review (kappa = 0.92). Conclusions. Risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, and several comorbid medical conditions. These results demonstrate that the Department of Veterans Affairs' national administrative databases can be used to study rare adverse drug events. C1 [McDonald, Jay R.; Zeringue, Angelique L.; Xian, Hong; Eisen, Seth A.] St Louis Vet Affairs Med Ctr, St Louis, MO 63106 USA. [McDonald, Jay R.; Zeringue, Angelique L.; Ranganathan, Prabha; Xian, Hong; Fraser, Victoria J.; Eisen, Seth A.] Washington Univ, St Louis, MO USA. [Burroughs, Thomas E.] St Louis Univ, St Louis, MO 63103 USA. [Caplan, Liron] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, Denver, CO USA. [Cunningham, Fran] Vet Affairs Pharm Benefits Management, Hines, IL USA. RP McDonald, JR (reprint author), St Louis Vet Affairs Med Ctr, Mail Code 111-JC,915 N Grand Blvd, St Louis, MO 63106 USA. EM Jay.McDonald1@va.gov RI Zeringue, Angelique/I-1755-2012 FU US Department of Veterans Affairs; Veterans Health Administration [IAF 06-026]; National Institutes of Health [K12RR023249, KL2RR024994] FX Financial support. US Department of Veterans Affairs, Veterans Health Administration (Health Services Research and Development Service project IAF 06-026); and National Institutes of Health (K12RR023249 and KL2RR024994). NR 32 TC 104 Z9 108 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2009 VL 48 IS 10 BP 1364 EP 1371 DI 10.1086/598331 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 441DK UT WOS:000265749300006 PM 19368499 ER PT J AU Palacios, E Dallman, R Munoz, M Hurtado, R Chalco, K Guerra, D Mestanza, L Llaro, K Bonilla, C Drobac, P Bayona, J Lygizos, M Anger, H Shin, S AF Palacios, Eda Dallman, Rebecca Munoz, Maribel Hurtado, Rocio Chalco, Katiuska Guerra, Dalia Mestanza, Lorena Llaro, Karim Bonilla, Cesar Drobac, Peter Bayona, Jaime Lygizos, Melissa Anger, Holly Shin, Sonya TI Drug-Resistant Tuberculosis and Pregnancy: Treatment Outcomes of 38 Cases in Lima, Peru SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PULMONARY TUBERCULOSIS; WOMEN; EPIDEMIOLOGY; MANAGEMENT; CHILDREN; DISEASE AB Background. Multidrug-resistant tuberculosis (MDR-TB) disproportionately affects young adults, including women of childbearing age; however, treatment of MDR-TB during pregnancy is still controversial. This study looks at the treatment and pregnancy outcomes in a cohort of women who were treated for MDR-TB during pregnancy during a period of 10 years. Methods. A retrospective case study was performed using a standardized data collection form and data from 3 ranked sources of patient records. All 38 participants were treated during pregnancy with individualized regimens that included second-line TB medications. We examined the frequency of favorable and adverse outcomes with regard to disease and pregnancy. Results. After completion of MDR-TB treatment, 61% of the women were cured, 13% had died, 13% had defaulted, 5% remained in treatment, and 5% had experienced treatment failure. Four of the women experienced clinical deterioration of TB during pregnancy. Five of the pregnancies terminated in spontaneous abortions, and 1 child was stillborn. Among the living newborns, 3 were born with low birth weight, 1 was born prematurely, and 1 had fetal distress. Conclusions. The rates of success in treating MDR-TB in our cohort are comparable to those of other MDR-TB treatment programs in Peru. The birth outcomes of our cohort are similar to those among the general Peru population. Therefore, we advocate that a woman should be given the option to continue treatment of MDR-TB rather than terminating pregnancy or discontinuing MDR-TB treatment. C1 [Palacios, Eda] Socios En Salud, RPB, Sucursal Peru, Lima, Peru. [Bonilla, Cesar] Natl TB Program, Lima, Peru. [Dallman, Rebecca] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Hurtado, Rocio] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Drobac, Peter; Shin, Sonya] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lygizos, Melissa] Univ Michigan, Sch Med, Ann Arbor, MI USA. RP Palacios, E (reprint author), Socios En Salud, RPB, Sucursal Peru, Av Merino Reyna 575, Lima, Peru. EM epalacios_ses@pih.org FU Socios En Salud and the Brigham and Women's Hospital; Bill and Melinda Gates Foundation; Thomas J. White, and the Global Fund to Fight AIDS, Tuberculosis, and Malaria FX Potential conflicts of interest. All authors: no conflicts. NR 26 TC 19 Z9 19 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2009 VL 48 IS 10 BP 1413 EP 1419 DI 10.1086/598191 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 441DK UT WOS:000265749300013 PM 19361302 ER PT J AU Serluca, FC Xu, B Okabe, N Baker, K Lin, SY Sullivan-Brown, J Konieczkowski, DJ Jaffe, KM Bradner, JM Fishman, MC Burdine, RD AF Serluca, Fabrizio C. Xu, Bo Okabe, Noriko Baker, Kari Lin, Shin-Yi Sullivan-Brown, Jessica Konieczkowski, David J. Jaffe, Kimberly M. Bradner, Joshua M. Fishman, Mark C. Burdine, Rebecca D. TI Mutations in zebrafish leucine-rich repeat-containing six-like affect cilia motility and result in pronephric cysts, but have variable effects on left-right patterning SO DEVELOPMENT LA English DT Article DE Zebrafish; seahorse; Lrrc6l; Cilia motility; Asymmetry; Pronephros; Cysts; Kupffer's vesicle ID POLYCYSTIC KIDNEY-DISEASE; LEFT-RIGHT ASYMMETRY; KUPFFERS VESICLE; PROTEIN; GENE; EXPRESSION; DIFFERENTIATION; IDENTIFICATION; BIOGENESIS; PATHWAYS AB Cilia defects have been implicated in a variety of human diseases and genetic disorders, but how cilia motility contributes to these phenotypes is still unknown. To further our understanding of how cilia function in development, we have cloned and characterized two alleles of seahorse, a zebrafish mutation that results in pronephric cysts. seahorse encodes Lrrc6l, a leucine-rich repeat-containing protein that is highly conserved in organisms that have motile cilia. seahorse is expressed in zebrafish tissues known to contain motile cilia. Although mutants do not affect cilia structure and retain the ability to interact with Disheveled, both alleles of seahorse strongly affect cilia motility in the zebrafish pronephros and neural tube. Intriguingly, although seahorse mutations variably affect fluid flow in Kupffer's vesicle, they can have very weak effects on left-right patterning. Combined with recently published results, our alleles suggest that the function of seahorse in cilia motility is separable from its function in other cilia-related phenotypes. C1 [Serluca, Fabrizio C.; Fishman, Mark C.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Xu, Bo; Okabe, Noriko; Baker, Kari; Lin, Shin-Yi; Sullivan-Brown, Jessica; Konieczkowski, David J.; Jaffe, Kimberly M.; Bradner, Joshua M.; Burdine, Rebecca D.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. RP Serluca, FC (reprint author), Novartis Inst Biomed Res, Cambridge, MA 02139 USA. EM fabrizio.serluca@novartis.com; rburdine@princeton.edu OI Burdine, Rebecca/0000-0001-6620-5015 FU New Jersey Commission on Cancer Research [05-2411-CCR-E0, 04-2405-CCR-E0]; National Science Foundation; American Heart Association [0825952D]; Edward Mallinckrodt Jr Foundation; Polycystic Kidney Disease Foundation [117b2r]; National Institutes of Child Health and Human Development [1R01HD048584]; NIH/NIGMS [P50GM071508] FX We thank Robert Geisler and Silke Geiger-Rudolph for the original bulked segregant analysis that placed seatg238a on chromosome 2; John Mably for advice on positional cloning; Christine Hostetter, Heather McAllister and Jaclyn Taylor for zebrafish care; Peggy Bisher for assistance with TEM; Stephan Y. Thiberge for assistance with video microscopy; Ray Habas for disheveled constructs; and the members of the Burdine and Fishman laboratories for helpful discussions. We thank Jonathan Eggenschwiler, Jack Lee, Kim Poole and Jodi Schottenfeld for participating in the blind test of KV flow. J. S. B. is supported by predoctoral award 05-2411-CCR-E0 from the New Jersey Commission on Cancer Research. S.-Y. L. is supported by a Graduate Research Fellowship from the National Science Foundation. K. M. J. is supported by postdoctoral grant 0825952D from the American Heart Association. R. D. B. is the 44th Scholar of the Edward Mallinckrodt Jr Foundation, and funds from this award were used in support of this work. Funds from awards to R. D. B. from the New Jersey Commission on Cancer Research (04-2405-CCR-E0), from the Polycystic Kidney Disease Foundation, (#117b2r) and from the National Institutes of Child Health and Human Development (1R01HD048584) were used in support of this work. Video imaging was performed in the Princeton Imaging Facility, which is supported by grant P50GM071508 from NIH/NIGMS. Deposited in PMC for release after 12 months. NR 47 TC 38 Z9 39 U1 1 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY 15 PY 2009 VL 136 IS 10 BP 1621 EP 1631 DI 10.1242/dev.020735 PG 11 WC Developmental Biology SC Developmental Biology GA 438AV UT WOS:000265529200005 PM 19395640 ER PT J AU Guseh, JS Bores, SA Stanger, BZ Zhou, Q Anderson, WJ Melton, DA Rajagopal, J AF Guseh, J. Sawalla Bores, Sam A. Stanger, Ben Z. Zhou, Qiao Anderson, William J. Melton, Douglas A. Rajagopal, Jayaraj TI Notch signaling promotes airway mucous metaplasia and inhibits alveolar development SO DEVELOPMENT LA English DT Article DE Airway epithelial cell fate; Lung disease; Notch; Mouse ID GOBLET CELL HYPERPLASIA; LUNG DEVELOPMENT; NEUROENDOCRINE DIFFERENTIATION; EMBRYONIC LETHALITY; PROGENITOR CELLS; IN-VIVO; EPITHELIUM; MICE; ACTIVATION; ASTHMA AB The airways are conduits that transport atmospheric oxygen to the distal alveolus. Normally, airway mucous cells are rare. However, diseases of the airway are often characterized by mucous metaplasia, in which there are dramatic increases in mucous cell numbers. As the Notch pathway is known to regulate cell fate in many contexts, we misexpressed the active intracellular domain of the mouse Notch1 receptor in lung epithelium. Notch misexpression resulted in an increase in mucous cells and a decrease in ciliated cells in the airway. Similarly, mouse embryonic tracheal explants and adult human airway epithelium treated with Notch agonists displayed increased mucous cell numbers and decreased ciliated cell numbers. Notch antagonists had the opposite effect. Notably, Notch antagonists blocked IL13-induced mucous metaplasia. IL13 has a well-established role as an inflammatory mediator of mucous metaplasia and functions through Stat6-mediated gene transcription. We found that Notch ligands, however, are able to cause mucous metaplasia in Stat6-null cultured trachea, thus identifying a novel pathway that stimulates mucous metaplasia. Notch signaling may therefore play an important role in airway disease and, by extension, Notch antagonists may have therapeutic value. Conversely, in the distal lung, Notch misexpression prevented the differentiation of alveolar cell types. Instead, the distal lung formed cysts composed of cells that were devoid of alveolar markers but that expressed some, but not all, markers of proximal airway epithelium. Occasional distal cystic cells appeared to differentiate into normal proximal airway cells, suggesting that ectopic Notch signaling arrests the normal differentiation of distal lung progenitors before they initiate an alveolar program. C1 [Guseh, J. Sawalla; Bores, Sam A.; Zhou, Qiao; Anderson, William J.; Melton, Douglas A.; Rajagopal, Jayaraj] Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Guseh, J. Sawalla; Bores, Sam A.; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Stanger, Ben Z.] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Div Gastroenterol, Philadelphia, PA 19104 USA. RP Rajagopal, J (reprint author), Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM jrajagopal@partners.org FU NHLBI [HL076393] FX We thank George Kenty and Ginna Smith-Bronstein for technical assistance and we thank Paul Danielian and Julie West for assistance with E2F4 staining. D. A. M. is an HHMI Investigator. J.R. is supported by NHLBI HL076393. Deposited in PMC for release after 6 months. NR 34 TC 115 Z9 117 U1 0 U2 10 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY 15 PY 2009 VL 136 IS 10 BP 1751 EP 1759 DI 10.1242/dev.029249 PG 9 WC Developmental Biology SC Developmental Biology GA 438AV UT WOS:000265529200017 PM 19369400 ER PT J AU Guthrie, CR Schellenberg, GD Kraemer, BC AF Guthrie, Chris R. Schellenberg, Gerard D. Kraemer, Brian C. TI SUT-2 potentiates tau-induced neurotoxicity in Caenorhabditis elegans SO HUMAN MOLECULAR GENETICS LA English DT Article ID PUROMYCIN-SENSITIVE AMINOPEPTIDASE; C-ELEGANS; FRONTOTEMPORAL DEMENTIA; AGGRESOME FORMATION; MISFOLDED PROTEINS; ALZHEIMERS-DISEASE; PRION PROTEIN; MUTATIONS; GENE; TAUOPATHY AB Expression of human tau in Caenorhabditis elegans neurons causes accumulation of aggregated tau leading to neurodegeneration and uncoordinated movement. We used this model of human tauopathy disorders to screen for genes required for tau neurotoxicity. Recessive loss-of-function mutations in the sut-2 locus suppress the Unc phenotype, tau aggregation and neurodegenerative changes caused by human tau. We cloned the sut-2 gene and found it encodes a novel sub-type of CCCH zinc finger protein conserved across animal phyla. SUT-2 shares significant identity with the mammalian SUT-2 (MSUT-2). To identify SUT-2 interacting proteins, we conducted a yeast two hybrid screen and found SUT-2 binds to ZYG-12, the sole C. elegans HOOK protein family member. Likewise, SUT-2 binds ZYG-12 in in vitro protein binding assays. Furthermore, loss of ZYG-12 leads to a marked upregulation of SUT-2 protein supporting the connection between SUT-2 and ZYG-12. The human genome encodes three homologs of ZYG-12: HOOK1, HOOK2 and HOOK3. Of these, the human ortholog of SUT-2 (MSUT-2) binds only to HOOK2 suggesting the interaction between SUT-2 and HOOK family proteins is conserved across animal phyla. The identification of sut-2 as a gene required for tau neurotoxicity in C. elegans may suggest new neuroprotective strategies capable of arresting tau pathogenesis in tauopathy disorders. C1 [Guthrie, Chris R.; Schellenberg, Gerard D.; Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Guthrie, Chris R.; Schellenberg, Gerard D.; Kraemer, Brian C.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA. [Schellenberg, Gerard D.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Kraemer, BC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, S182,1660 S Columbian Way, Seattle, WA 98108 USA. EM kraemerb@u.washington.edu FU Department of Veterans Affairs Merit Review; NIA [PO1 AG17586] FX This work was supported by Department of Veterans Affairs Merit Review Grant ( B. C. K.) and by NIA grant PO1 AG17586 ( G. D. S.). NR 57 TC 47 Z9 54 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 15 PY 2009 VL 18 IS 10 BP 1825 EP 1838 DI 10.1093/hmg/ddp099 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 437ZJ UT WOS:000265525400009 PM 19273536 ER PT J AU Salomatina, E Muzikansky, A Neel, V Yaroslavsky, AN AF Salomatina, Elena Muzikansky, Alona Neel, Victor Yaroslavsky, Anna N. TI Multimodal optical imaging and spectroscopy for the intraoperative mapping of nonmelanoma skin cancer SO JOURNAL OF APPLIED PHYSICS LA English DT Article DE biomedical optical imaging; cancer; cellular biophysics; fluorescence; image registration; light polarisation; medical image processing; reflectivity; skin; spectral analysis; statistical testing; surgery; tumours ID BASAL-CELL CARCINOMA; METHYLENE-BLUE; METAPLASIA; TUMORS AB Basal cell carcinoma (BCC) is the most common human malignancy, and its incidence increases yearly. In this contribution we investigate the feasibility of combining multimodal reflectance and fluorescence polarization imaging (RFPI) with spectroscopic analysis of the reflectance images for facilitating intraoperative delineation of BCCs. Twenty fresh thick BCC specimens were obtained within 1 h after Mohs micrographic surgeries. The samples were soaked for up to 2 min in an aqueous 0.2 mg/ml solution of methylene blue, briefly rinsed in saline solution, and imaged. Reflectance images were acquired in the range from 395 to 735 nm, with steps of 10 nm. Fluorescence polarization images were excited at 630 nm and registered in the range between 660 and 750 nm. The results yielded by RFPI were qualitatively compared to each other and to histopathology. From the copolarized reflectance images the spectral responses including the optical densities and their wavelength derivatives were calculated. The differences in the spectral responses of the benign and malignant stained skin structures were assessed. Statistical analysis, i.e., Student's t-test, was employed to verify the significance of the discovered differences. Both reflectance and fluorescence polarization images correlated well with histopathology in all the cases. Reflectance polarization images provided more detailed information on skin morphology, with the appearance of skin structures resembling that of histopathology. Fluorescence polarization images exhibited higher contrast of cancerous tissue as compared to reflectance imaging. The analysis of the optical densities and their wavelength derivatives for tumor and normal tissues has confirmed statistical significance of the differences that can be used for intraoperative cancer delineation. The results of the study indicate that spectral analysis is a useful adjunct to RFPI for facilitating skin cancer delineation. C1 [Salomatina, Elena; Yaroslavsky, Anna N.] Wellman Ctr Photomed, Boston, MA 02114 USA. [Salomatina, Elena; Muzikansky, Alona; Neel, Victor; Yaroslavsky, Anna N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Neel, Victor; Yaroslavsky, Anna N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Yaroslavsky, AN (reprint author), Wellman Ctr Photomed, Boston, MA 02114 USA. EM yaroslav@helix.mgh.harvard.edu FU National Institutes of Health [R01 EB002423-01] FX Help with the histopathological analysis provided by Dr. Munir Al-Arashi is gratefully acknowledged. This study was funded by the National Institutes of Health (Grant No. R01 EB002423-01) NR 19 TC 3 Z9 3 U1 1 U2 2 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-8979 J9 J APPL PHYS JI J. Appl. Phys. PD MAY 15 PY 2009 VL 105 IS 10 AR 102010 DI 10.1063/1.3115646 PG 7 WC Physics, Applied SC Physics GA 451VX UT WOS:000266500100011 ER PT J AU Watanabe, H Smith, MJ Heilig, E Beglopoulos, V Kelleher, RJ Shen, J AF Watanabe, Hirotaka Smith, Miriam J. Heilig, Elizabeth Beglopoulos, Vassilios Kelleher, Raymond J., III Shen, Jie TI Indirect Regulation of Presenilins in CREB-mediated Transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELEMENT-BINDING PROTEIN; ALZHEIMERS-DISEASE; PROTEOLYTIC RELEASE; GAMMA-SECRETASE; STEM-CELLS; EXPRESSION; ERK; PHOSPHORYLATION; PATHWAY; KINASE AB Presenilins are essential for synaptic function, memory formation, and neuronal survival. Previously, we reported that expression of cAMP response element-binding protein (CREB) target genes is reduced in the cerebral cortex of presenilin (PS) conditional double knock-out (cDKO) mice. To determine whether the reduced expression of the CREB target genes in these mutant mice is due to loss of presenilin directly or secondary to the impaired neuronal activity, we established a sensitive luciferase reporter system to assess direct transcriptional regulation in cultured cells. We first used immortalized PS-deficient mouse embryonic fibroblasts (MEFs), and found that both CREB-mediated transcription and Notch-mediated HES1 transcription are decreased. However, the ubiquitin-C promoter-mediated transcription is also reduced, and among these three reporters, transfection of exogenous PS1 can rescue only the Notch-mediated HES1 transcription. Further Northern analysis revealed transcriptional alterations of Creb, ubiquitin-C, and other housekeeping genes in PS-deficient MEFs, indicating transcriptional dysregulation in these cells. We then used the Cre/loxP system to develop a postnatal PS-deficient cortical neuronal culture. Surprisingly, in these PS-null neurons, CREB-mediated transcription is not significantly decreased, and levels of total and phosphorylated CREB proteins are unchanged as well. Notch-mediated HES1 transcription is markedly reduced, and this reduction can be rescued by exogenous PS1. Together, our findings suggest that CREB-mediated transcription is regulated indirectly by PS in the adult cerebral cortex, and that attenuation of CREB target gene expression in PS cDKO mice is likely due to reduced neuronal activity in these mutant brains. C1 [Watanabe, Hirotaka; Smith, Miriam J.; Beglopoulos, Vassilios; Shen, Jie] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Heilig, Elizabeth; Kelleher, Raymond J., III] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02115 USA. RP Shen, J (reprint author), Harvard New Res Bldg,Rm 636E,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM jshen@rics.bwh.harvard.edu RI Smith, Miriam/J-4001-2015 OI Smith, Miriam/0000-0002-3184-0817 FU National Institutes of Health [NS41783] FX This work was supported, in whole or in part, by National Institutes of Health Grant NS41783 (to J. S.). NR 45 TC 19 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 15 PY 2009 VL 284 IS 20 BP 13705 EP 13713 DI 10.1074/jbc.M809168200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442YL UT WOS:000265877300048 PM 19289467 ER PT J AU Sundararaj, KP Samuvel, DJ Li, YC Sanders, JJ Lopes-Virella, MF Huang, Y AF Sundararaj, Kamala P. Samuvel, Devadoss J. Li, Yanchun Sanders, John J. Lopes-Virella, Maria F. Huang, Yan TI Interleukin-6 Released from Fibroblasts Is Essential for Up-regulation of Matrix Metalloproteinase-1 Expression by U937 Macrophages in Coculture CROSS-TALKING BETWEEN FIBROBLASTS AND U937 MACROPHAGES EXPOSED TO HIGH GLUCOSE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERIODONTAL-DISEASE; GINGIVAL FIBROBLASTS; TISSUE INHIBITOR; GENE-EXPRESSION; KAPPA-B; COLLAGENASE; CELLS; HISTIOCYTES; INVOLVEMENT; ACTIVATION AB Matrix metalloproteinases (MMPs) play a key role in periodontal disease. Although it is known that macrophages and fibroblasts are co-localized and express MMPs in the diseased periodontal tissue, the effect of interaction between these two cell types on MMP expression has not been well elucidated. Furthermore although it is known that diabetes is associated with accelerated periodontal tissue destruction, it remains unknown whether hyperglycemia, a major metabolic abnormality in diabetes, regulates MMP expression by affecting the cross-talking between fibroblasts and macrophages. In this study, human gingival fibroblasts and U937 macrophages were cocultured in a two-compartment transwell culture system, and the cells were treated with normal or high glucose. We found that coculture of fibroblasts and U937 macrophages led to an augmentation of MMP-1 expression by U937 macrophages, and high glucose further enhanced this augmentation. Similar observations were also made in the coculture of fibroblasts and human primary monocytes. We also found that interleukin 6 (IL-6) released by fibroblasts was essential for the augmentation of MMP-1 expression by U937 macrophages. Furthermore our results showed that high glucose, IL-6, and lipopolysaccharide had a synergistic effect on MMP-1 expression. Finally our study indicated that MAPK pathways and activator protein-1 transcription factor were involved in the coculture- and high glucose-augmented MMP-1 expression. In conclusion, this study demonstrates that IL-6 derived from fibroblasts is essential for MMP-1 up-regulation by cross-talking between fibroblasts and U937 macrophages exposed to high glucose, revealing an IL-6-dependent mechanism in MMP-1 up-regulation. C1 [Li, Yanchun; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. [Sundararaj, Kamala P.; Samuvel, Devadoss J.; Lopes-Virella, Maria F.; Huang, Yan] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Sanders, John J.] Med Univ S Carolina, Coll Dent Med, Dept Stomatol, Charleston, SC 29403 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU National Institutes of Health [DE16353]; Department of Veterans Affairs FX This work was supported, in whole or in part, by National Institutes of Health Grant DE16353 (to Y. H.). This work was also supported by a merit review grant from the Department of Veterans Affairs (to Y. H.). NR 35 TC 41 Z9 41 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 15 PY 2009 VL 284 IS 20 BP 13714 EP 13724 DI 10.1074/jbc.M806573200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442YL UT WOS:000265877300049 PM 19307187 ER PT J AU Dagda, RK Cherra, SJ Kulich, SM Tandon, A Park, D Chu, CT AF Dagda, Ruben K. Cherra, Salvatore J., III Kulich, Scott M. Tandon, Anurag Park, David Chu, Charleen T. TI Loss of PINK1 Function Promotes Mitophagy through Effects on Oxidative Stress and Mitochondrial Fission SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; PARKINSONS-DISEASE; CELL-DEATH; RECESSIVE PARKINSONISM; DOPAMINERGIC-NEURONS; ALZHEIMERS-DISEASE; MAMMALIAN-CELLS; SH-SY5Y CELLS; AUTOPHAGY; MUTATIONS AB Mitochondrial dysregulation is strongly implicated in Parkinson disease. Mutations in PTEN-induced kinase 1 (PINK1) are associated with familial parkinsonism and neuropsychiatric disorders. Although overexpressed PINK1 is neuroprotective, less is known about neuronal responses to loss of PINK1 function. We found that stable knockdown of PINK1 induced mitochondrial fragmentation and autophagy in SH-SY5Y cells, which was reversed by the reintroduction of an RNA interference (RNAi)-resistant plasmid for PINK1. Moreover, stable or transient overexpression of wild-type PINK1 increased mitochondrial interconnectivity and suppressed toxin-induced autophagy/mitophagy. Mitochondrial oxidant production played an essential role in triggering mitochondrial fragmentation and autophagy in PINK1 shRNA lines. Autophagy/mitophagy served a protective role in limiting cell death, and overexpressing Parkin further enhanced this protective mitophagic response. The dominant negative Drp1 mutant inhibited both fission and mitophagy in PINK1-deficient cells. Interestingly, RNAi knockdown of autophagy proteins Atg7 and LC3/Atg8 also decreased mitochondrial fragmentation without affecting oxidative stress, suggesting active involvement of autophagy in morphologic remodeling of mitochondria for clearance. To summarize, loss of PINK1 function elicits oxidative stress and mitochondrial turnover coordinated by the autophagic and fission/fusion machineries. Furthermore, PINK1 and Parkin may cooperate through different mechanisms to maintain mitochondrial homeostasis. C1 [Dagda, Ruben K.; Cherra, Salvatore J., III; Kulich, Scott M.; Chu, Charleen T.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. [Chu, Charleen T.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15213 USA. [Kulich, Scott M.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Tandon, Anurag] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON M55 3H2, Canada. [Park, David] Univ Ottawa, Neurosci Grp, Ottawa Hlth Res Inst, Ottawa, ON K1H 8M5, Canada. RP Chu, CT (reprint author), Univ Pittsburgh, Dept Pathol, 200 Lothrop St, Pittsburgh, PA 15261 USA. EM ctc4@pitt.edu RI Chu, Charleen/B-1601-2008; OI Chu, Charleen/0000-0002-5052-8271; Dagda, Ruben/0000-0002-9946-9591 FU National Institutes of Health [AG026389, DC009120, NS053777, F32 AG030821]; Pittsburgh Foundation, Emmerling Fund; American Parkinson Disease Association; Veterans Administration Advanced Career Development Award FX Supported in part by National Institutes of Health Grant F32 AG030821. NR 60 TC 393 Z9 399 U1 6 U2 50 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 15 PY 2009 VL 284 IS 20 BP 13843 EP 13855 DI 10.1074/jbc.M808515200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442YL UT WOS:000265877300061 PM 19279012 ER PT J AU Brooks-Worrell, B Warsen, A Palmer, JP AF Brooks-Worrell, Barbara Warsen, Adelaide Palmer, Jerfy P. TI Improved T cell assay for identification of type 1 diabetes patients SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Type 1 diabetes; Islet proteins; T cells; Immune monitoring; T cell assay ID IMMUNE-RESPONSES; ISLET PROTEINS; ANTIGENS; ANTIBODIES; MELLITUS; LYMPHOCYTES; ONSET; PANCREAS; DISEASE; LYT-2+ AB Diabetes mellitus is comprised primarily of two clinically separate diseases: type 1 (T1D) and type 2 diabetes (T2D). T1D is a cell-mediated autoimmune disease directed against the beta cells and characterized by autoantibody (Ab) and T cell reactivity to islet proteins whereas, T2D is non-autoimmune. Despite the fact that the pathological process in autoimmune diabetes involves T cells, immune markers of diabetes have primarily centered on the presence of circulating serum islet autoantibodies. In two masked NIH sponsored workshops, our cellular immunoblotting T cell assay. which uses isolated human islets separated into 18 molecular weight fractions, has been validated to be able to distinguish T1D patients from controls with excellent specificity and sensitivity. In this study. we utilized the first workshop to select eight molecular weight fractions of human islets that were the most discriminatory between T1D patients and controls. Using these eight molecular weight fractions identified in the first workshop, we validated the preferential recognition of these 8 blot sections in a second workshop. We then re-calculated the sensitivity and specificity of the cellular immunoblotting assay for both workshops using only the data from these 8 blot sections. We observed increases in both sensitivity and specificity compared to the original workshop data for both workshops. The use of 8 instead of 18 molecular weight regions allows for a significant reduction in the amount of blood needed from patients, thus allowing cellular immunoblotting to be performed on pediatric patients participating in immunomodulatory studies. This improved T cell assay, which directly measures islet reactive T cell responses in autoimmune diabetes patients with excellent sensitivity and specificity, will likely improve patient follow-up during intervention studies. (C) 2009 Elsevier B.V. All rights reserved. C1 [Brooks-Worrell, Barbara; Warsen, Adelaide; Palmer, Jerfy P.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Brooks-Worrell, B (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way,Bldg 1,Room 609, Seattle, WA 98108 USA. EM bbrooks@u.washington.edu FU National Institute of Health [P01-DK053004, P30-DK17047, M01-RR00037] FX The following National Institute of Health grants provided partial support: P01-DK053004, P30-DK17047, and M01-RR00037. NR 28 TC 13 Z9 14 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 MAY 15 PY 2009 VL 344 IS 1 BP 79 EP 83 DI 10.1016/j.jim.2009.03.004 PG 5 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 452WW UT WOS:000266572900010 PM 19328805 ER PT J AU Kaufmann, DE Walker, BD AF Kaufmann, Daniel E. Walker, Bruce D. TI PD-1 and CTLA-4 Inhibitory Cosignaling Pathways in HIV Infection and the Potential for Therapeutic Intervention SO JOURNAL OF IMMUNOLOGY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHRONIC VIRAL-INFECTION; T-CELL EXHAUSTION; UP-REGULATION; DISEASE PROGRESSION; DENDRITIC CELLS; COSTIMULATORY MOLECULE; METASTATIC MELANOMA; PROGRAMMED DEATH-1; IMMUNE ACTIVATION AB The balance between proinflammatory mechanisms and the dampening of excessive immune activation is critical for successful clearance of a pathogen without harm to the host. In particular, molecules of the B7:CD28 family play a critical role in regulating T cell activation and peripheral tolerance. Chronic pathogens like HIV, which is characterized by ongoing viral replication despite detectable virus-specific T cell responses, and cancer cells have exploited these pathways to attenuate Ag-specific T cell immunity. This review summarizes evidence that molecules of the B7:CD28 family, PD-1, CTLA-4 and their ligands, play an active and reversible role in virus-specific T cell exhaustion associated with HIV infection in humans and in the SIV model in macaques. We discuss the potential for immunotherapeutic interventions based on manipulation of these inhibitory, networks, the promising data obtained with blockade of the PD-1 pathway in animal models, and the challenges to such therapies. The Journal of Immunology, 2009, 182: 5891-5897. C1 [Kaufmann, Daniel E.; Walker, Bruce D.] Massachusetts Gen Hosp E, Ragon Inst, Massachusetts Gen Hosp, MIT, Charlestown, MA 02129 USA. [Kaufmann, Daniel E.; Walker, Bruce D.] Harvard, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. RP Kaufmann, DE (reprint author), Massachusetts Gen Hosp E, Ragon Inst, Massachusetts Gen Hosp, MIT, Room 6618B,149 13th St, Charlestown, MA 02129 USA. EM dkaufmann@partners.org FU Howard Hughes Medical Institute; NHLBI NIH HHS [R01 HL092565]; NIAID NIH HHS [P30 AI060354, P01 AI080192, R01 AI030914] NR 70 TC 121 Z9 129 U1 0 U2 11 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2009 VL 182 IS 10 BP 5891 EP 5897 DI 10.4049/jimmunol.0803771 PG 7 WC Immunology SC Immunology GA 443HC UT WOS:000265899800003 PM 19414738 ER PT J AU Call, MJ Xing, XC Cuny, GD Seth, NP Altmann, DM Fugger, L Krogsgaard, M Stein, RL Wucherpfennig, KW AF Call, Melissa J. Xing, Xuechao Cuny, Gregory D. Seth, Nilufer P. Altmann, Daniel M. Fugger, Lars Krogsgaard, Michelle Stein, Ross L. Wucherpfennig, Kai W. TI In Vivo Enhancement of Peptide Display by MHC Class II Molecules with Small Molecule Catalysts of Peptide Exchange SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HLA-DR MOLECULES; MYELIN BASIC-PROTEIN; CD4 T-CELLS; MULTIPLE-SCLEROSIS; ANTIGEN PRESENTATION; CRYSTAL-STRUCTURE; RECEPTIVE STATE; LYSOSOMAL PH; LYMPH-NODES; B-CELLS AB Rapid binding of peptides to MHC class II molecules is normally limited to a deep endosomal compartment where the coordinate action of low pH and HLA-DM displaces the invariant chain remnant CLIP or other peptides from the binding site. Exogenously added peptides are subject to proteolytic degradation for extended periods of time before they reach the relevant endosomal compartment, which limits the efficacy of peptide-based vaccines and therapeutics. In this study, we describe a family of small molecules that substantially accelerate the rate of peptide binding to HLA-DR molecules in the absence of HLA-DM. A structure-activity relationship study resulted in analogs with significantly higher potency and also defined key structural features required for activity. These compounds are active over a broad pH range and thus enable efficient peptide loading at the cell surface. The small molecules not only enhance peptide presentation by APC in vitro, but are also active in vivo where they substantially increase the fraction of APC on which displayed peptide is detectable. We propose that the small molecule quickly reaches draining lymph nodes along with the coadministered peptide and induces rapid loading of peptide before it is destroyed by proteases. Such compounds may be useful for enhancing the efficacy of peptide-based vaccines and other therapeutics that require binding to MHC class II molecules. The Journal of Immunology, 2009, 182: 6342-6352. C1 [Call, Melissa J.; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Xing, Xuechao; Cuny, Gregory D.; Stein, Ross L.] Harvard Univ, Sch Med, Lab Drug Discovery Neurodegenerat, Harvard NeuroDiscovery Ctr, Boston, MA 02115 USA. [Cuny, Gregory D.; Stein, Ross L.; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. [Seth, Nilufer P.] Wyeth Res, Inflammat Discovery Res, Cambridge, MA 02140 USA. [Altmann, Daniel M.] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis & Immun, Hammersmith Hosp, London, England. [Fugger, Lars] Univ Oxford, John Radcliffe Hosp, Dept Clin Neurol, Weatherall Inst Mol Med, Oxford OX3 9DU, England. [Krogsgaard, Michelle] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Krogsgaard, Michelle] NYU, Sch Med, Inst Canc, New York, NY 10016 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Dona Bldg,Room 1410,44 Binney St, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu OI Altmann, Daniel/0000-0002-2436-6192 FU NIAID NIH HHS [P01 AI045757, P01 AI045757-10, P01AI045757, R01 AI057493, R01 AI057493-05, R01AI57493]; NINDS NIH HHS [R01 NS044914, R01 NS044914-05A1, R01NS044914, R21 NS067497] NR 48 TC 21 Z9 21 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2009 VL 182 IS 10 BP 6342 EP 6352 DI 10.4049/jimmunol.0803464 PG 11 WC Immunology SC Immunology GA 443HC UT WOS:000265899800052 PM 19414787 ER PT J AU Keller, CJ Cash, SS Narayanan, S Wang, CM Kuzniecky, R Carlson, C Devinsky, O Thesen, T Doyle, W Sassaroli, A Boas, DA Ulbert, I Halgren, E AF Keller, Corey J. Cash, Sydney S. Narayanan, Suresh Wang, Chunmao Kuzniecky, Ruben Carlson, Chad Devinsky, Orrin Thesen, Thomas Doyle, Werner Sassaroli, Angelo Boas, David A. Ulbert, Istvan Halgren, Eric TI Intracranial microprobe for evaluating neuro-hemodynamic coupling in unanesthetized human neocortex SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Microelectrode; BOLD; Oxygenation; Hemodynamics; Neuro-hemodynamic coupling; Breath-hold; Electrocardiogram; Cortical electrical stimulation ID CURRENT-SOURCE-DENSITY; CEREBRAL-BLOOD-FLOW; RAT SOMATOSENSORY CORTEX; RODENT BARREL CORTEX; SPECTROSCOPIC ANALYSIS; GENERALIZED SEIZURES; ANURAN CEREBELLUM; SYNAPTIC ACTIVITY; FIELD POTENTIALS; CARBON-DIOXIDE AB Measurement of the blood-oxygen-level dependent (BOLD) response with fMRI has revolutionized cognitive neuroscience and is increasingly important in clinical care. The BOLD response reflects changes in deoxy-hemoglobin concentration, blood volume, and blood flow. These hemodynamic changes ultimately result from neuronal firing and synaptic activity, but the linkage between these domains is complex, poorly understood, and may differ across species, cortical areas, diseases, and cognitive states. We describe here a technique that can measure neural and hemodynamic changes simultaneously from cortical microdomains in waking humans. We utilize a "laminar optode," a linear array of microelectrodes for electrophysiological measures paired with a micro-optical device for hemodynamic measurements. Optical measurements include laser Doppler to estimate cerebral blood flow as well as point spectroscopy to estimate oxy- and deoxy-hemoglobin concentrations. The microelectrode array records local field potential gradients (PC) and multi-unit activity (MUA) at 24 locations spanning the cortical depth, permitting estimation of population trans-membrane current flows (Current Source Density. CSD) and population cell firing in each cortical lamina. Comparison of the laminar CSD/MUA profile with the origins and terminations of cortical circuits allows activity in specific neuronal circuits to be inferred and then directly compared to hemodynamics. Access is obtained in epileptic patients during diagnostic evaluation for surgical therapy. Validation tests with relatively well-understood manipulations (EKG, breath-holding, cortical electrical stimulation) demonstrate the expected responses. This device can provide a new and robust means for obtaining detailed, quantitative data for defining neurovascular coupling in awake humans. (C) 2009 Elsevier B.V. All rights reserved. C1 [Keller, Corey J.; Cash, Sydney S.; Narayanan, Suresh] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wang, Chunmao; Kuzniecky, Ruben; Carlson, Chad; Devinsky, Orrin; Thesen, Thomas; Doyle, Werner] NYU, Comprehens Epilepsy Ctr, Langone Med Ctr, New York, NY USA. [Sassaroli, Angelo] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. [Boas, David A.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ulbert, Istvan] Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. [Ulbert, Istvan] Peter Pazmany Catholic Univ, Dept Informat Technol, Budapest, Hungary. [Halgren, Eric] Univ Calif San Diego, Dept Radiol, Multimodal Imaging Lab, La Jolla, CA 92093 USA. RP Keller, CJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM cjkeller@partners.org; scash@partners.org; suresh.narayanan@ge.com; wangch@nidcd.nih.gov; ruben.kuzniecky@med.nyu.edu; ccarlso2@gmail.com; od4@nyu.edu; thomas.thesen@med.nyu.edu; wkd1@nyu.edu; angelo.sassaroli@tufts.edu; dboas@nmr.mgh.harvard.edu; ulbert@cogpsyphy.hu; ehalgren@ucsd.edu RI Ulbert, Istvan/F-2213-2010; OI Devinsky, Orrin/0000-0003-0044-4632 FU NIH [RO1-NS44623, NS18741] FX We would like to thank Andrew Dykstra, Alex Chan, Justine Cormier, and Nima Dehghani for excellent critique of this manuscript and Laszlo Papp for excellent technical support. This research is funded by NIH grants RO1-NS44623 and NS18741. NR 69 TC 10 Z9 10 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD MAY 15 PY 2009 VL 179 IS 2 BP 208 EP 218 DI 10.1016/j.jneumeth.2009.01.036 PG 11 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 438VZ UT WOS:000265585400008 PM 19428529 ER PT J AU Beckham, JD Tuttle, K Tyler, KL AF Beckham, J. David Tuttle, Kathryn Tyler, Kenneth L. TI Reovirus Activates Transforming Growth Factor beta and Bone Morphogenetic Protein Signaling Pathways in the Central Nervous System That Contribute to Neuronal Survival following Infection SO JOURNAL OF VIROLOGY LA English DT Article ID WEST-NILE-VIRUS; INDUCED APOPTOSIS REQUIRES; NF-KAPPA-B; CELL-DEATH; TGF-BETA; TISSUE-INJURY; JC VIRUS; IN-VITRO; REPLICATION; EXPRESSION AB Viral infections of the central nervous system (CNS) are important causes of worldwide morbidity and mortality, and understanding how viruses perturb host cell signaling pathways will facilitate identification of novel antiviral therapies. We now show that reovirus infection activates transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) signaling in a murine model of encephalitis in vivo. TGF-beta receptor I (TGF-beta RI) expression is increased and its downstream signaling factor, SMAD3, is activated in the brains of reovirus-infected mice. TGF-beta signaling is neuroprotective, as inhibition with a TGF-beta RI inhibitor increases death of infected neurons. Similarly, BMP receptor I expression is increased and its downstream signaling factor, SMAD1, is activated in reovirus-infected neurons in the brains of infected mice in vivo. Activated SMAD1 and SMAD3 were both detected in regions of brain infected by reovirus, but activated SMAD1 was found predominantly in uninfected neurons in close proximity to infected neurons. Treatment of reovirus-infected primary mouse cortical neurons with a BMP agonist reduced apoptosis. These data provide the first evidence for the activation of TGF-beta and BMP signaling pathways following neurotropic viral infection and suggest that these signaling pathways normally function as part of the host's protective innate immune response against CNS viral infection. C1 [Beckham, J. David; Tyler, Kenneth L.] Univ Colorado, Dept Med, Denver, CO 80045 USA. [Tuttle, Kathryn; Tyler, Kenneth L.] Univ Colorado, Dept Neurol, Denver, CO 80045 USA. [Tyler, Kenneth L.] Univ Colorado, Dept Microbiol, Denver, CO 80045 USA. [Beckham, J. David; Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Tyler, KL (reprint author), Univ Colorado Denver, Dept Neurol B182, 12700 E 19th Ave,Res Complex 2-5th Floor, Aurora, CO 80045 USA. EM Ken.Tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU VA Career Development Award-2; NIH [5K08AI076518, 5R01NS050138, 1R01NS051403] FX We express our thanks to Jennifer Smith Leser for technical support. This work was supported in part by VA Career Development Award-2, VA Merit funding, NIH 5K08AI076518, NIH 5R01NS050138, NIH 1R01NS051403, and ASCI Young Investigator Award. NR 45 TC 10 Z9 11 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 MAY 15 PY 2009 VL 83 IS 10 BP 5035 EP 5045 DI 10.1128/JVI.02433-08 PG 11 WC Virology SC Virology GA 436IS UT WOS:000265407700030 PM 19279118 ER PT J AU Mehta, S Li, HM Hogan, PG Cunningham, KW AF Mehta, Sohum Li, Huiming Hogan, Patrick G. Cunningham, Kyle W. TI Domain Architecture of the Regulators of Calcineurin (RCANs) and Identification of a Divergent RCAN in Yeast SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SYNDROME CRITICAL REGION; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; DOWN-SYNDROME; IN-VIVO; CARDIAC-HYPERTROPHY; CANDIDA-ALBICANS; CYCLOSPORINE-A; CRYPTOCOCCUS-NEOFORMANS; INTERACTING PROTEIN-1 AB Regulators of calcineurin (RCANs) in fungi and mammals have been shown to stimulate and inhibit calcineurin signaling in vivo through direct interactions with the catalytic subunit of the phosphatase. The dual effects of RCANs on calcineurin were examined by performing structure-function analyses on yeast Rcn1 and human RCAN1 (a.k.a. DSCR1, MCIP1, and calcipressin 1) proteins expressed at a variety of different levels in yeast. At high levels of expression, the inhibitory effects required a degenerate PxIxIT-like motif and a novel LxxP motif, which may be related to calcineurin-binding motifs in human NFAT proteins. The conserved glycogen synthase kinase 3 (GSK-3) phosphorylation site was not required for inhibition, suggesting that RCANs can simply compete with other substrates for docking onto calcineurin. In addition to these docking motifs, two other highly conserved motifs plus the GSK-3 phosphorylation site in RCANs, along with the E3 ubiquitin ligase SCF(Cdc4), were required for stimulation of calcineurin signaling in yeast. These findings suggest that RCANs may function primarily as chaperones for calcineurin biosynthesis or recycling, requiring binding, phosphorylation, ubiquitylation, and proteasomal degradation for their stimulatory effect. Finally, another highly divergent yeast RCAN, termed Rcn2 (YOR220w), was identified through a functional genetic screen. Rcn2 lacks all stimulatory motifs, though its expression was still strongly induced by calcineurin signaling through Crz1 and it competed with other endogenous substrates when overexpressed, similar to canonical RCANs. These findings suggest a primary role for canonical RCANs in facilitating calcineurin signaling, but canonical RCANs may secondarily inhibit calcineurin signaling by interfering with substrate interactions and enzymatic activity. C1 [Mehta, Sohum; Cunningham, Kyle W.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Li, Huiming] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Li, Huiming; Hogan, Patrick G.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Cunningham, KW (reprint author), Johns Hopkins Univ, Dept Biol, 3400 N Charles St, Baltimore, MD 21218 USA. EM kwc@jhu.edu FU NIAID NIH HHS [R01 AI040127, AI40127]; NIGMS NIH HHS [GM053082, R01 GM053082] NR 81 TC 44 Z9 44 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY 15 PY 2009 VL 29 IS 10 BP 2777 EP 2793 DI 10.1128/MCB.01197-08 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 439ZD UT WOS:000265665900023 PM 19273587 ER PT J AU Sutherland, APR Zhang, H Zhang, Y Michaud, M Xie, ZF Patti, ME Grusby, MJ Zhang, WJ AF Sutherland, Andrew P. R. Zhang, Hai Zhang, Ye Michaud, Monia Xie, Zhifang Patti, Mary-Elizabeth Grusby, Michael J. Zhang, Weiping J. TI Zinc Finger Protein Zbtb20 Is Essential for Postnatal Survival and Glucose Homeostasis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; GROWTH-FACTOR-I; PHOSPHOINOSITIDE 3-KINASE; HEPATIC GLUCOKINASE; P85-ALPHA SUBUNIT; INSULIN ACTION; HORMONE; EXPRESSION; LIVER; MICE AB Zbtb20 is a member of the POK family of proteins, which function primarily as transcriptional repressors via interactions mediated by their conserved C2H2 Kruppel type zinc finger and BTB/POZ domains. To define the function of Zbtb20 in vivo, we generated knockout mice by homologous recombination. Zbtb20 null mice display a stark phenotype characterized by postnatal growth retardation, metabolic dysfunction, and lethality. Zbtb20 knockout mice displayed abnormal glucose homeostasis, hormonal responses, and depletion of energy stores, consistent with an energetic deficit. Additionally, increased serum bilirubin and alanine aminotransferase levels were suggestive of liver dysfunction. To identify potential liver-specific Zbtb20 target genes, we performed transcript profiling studies on liver tissue from Zbtb20 knockout mice and wild-type littermate controls. These studies identified sets of genes involved in growth, metabolism, and detoxification that were differentially regulated in Zbtb20 knockout liver. Transgenic mice expressing Zbtb20 in the liver were generated and crossed onto the Zbtb20 knockout background, which resulted in no significant normalization of growth or glucose metabolism but a significant increase in life span compared to controls. These data indicate that the phenotype of Zbtb20 knockout mice results from liver-dependent and -independent defects, suggesting that Zbtb20 plays nonredundant roles in multiple organ systems. C1 [Sutherland, Andrew P. R.; Michaud, Monia; Grusby, Michael J.; Zhang, Weiping J.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Zhang, Hai; Zhang, Ye; Xie, Zhifang; Zhang, Weiping J.] Second Mil Med Univ, Dept Pathophysiol, Shanghai 200433, Peoples R China. [Patti, Mary-Elizabeth] Harvard Univ, Sch Med, Boston, MA USA. [Patti, Mary-Elizabeth] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Sutherland, Andrew P. R.] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 0200, Australia. RP Grusby, MJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 651 Huntington Ave, Boston, MA 02115 USA. EM mgrusby@hsph.harvard.edu; wzhang@smmu.edu.cn RI Sutherland, Andrew/B-6191-2012 OI Sutherland, Andrew/0000-0003-0366-9327 FU National 973 Program of China [2006CB503910]; NH&MRC of Australia FX We thank Kirsten Sigrist, Jennifer Donovan, Diana Pascual, and the staff at the Harvard School of Public Health Animal Testing Facility for assistance with animal care.; This work was supported by gift from the G. Harold and Leila Y. Mathers Charitable Foundation (to M. J. G.) and National 973 Program of China, grant 2006CB503910 (to W. J. Z.). A. P. R. Sutherland is a CJ Martin Fellow of the NH&MRC of Australia.; We have no conflicting financial interests. NR 34 TC 32 Z9 38 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY 15 PY 2009 VL 29 IS 10 BP 2804 EP 2815 DI 10.1128/MCB.01667-08 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 439ZD UT WOS:000265665900025 PM 19273596 ER PT J AU Callen, E Jankovic, M Wong, N Zha, S Chen, HT Difilippantonio, S Di Virgilio, M Heidkamp, G Alt, FW Nussenzweig, A Nussenzweig, M AF Callen, Elsa Jankovic, Mila Wong, Nancy Zha, Shan Chen, Hua-Tang Difilippantonio, Simone Di Virgilio, Michela Heidkamp, Gordon Alt, Frederick W. Nussenzweig, Andre Nussenzweig, Michel TI Essential Role for DNA-PKcs in DNA Double-Strand Break Repair and Apoptosis in ATM-Deficient Lymphocytes SO MOLECULAR CELL LA English DT Article ID DEPENDENT PROTEIN-KINASE; CLASS-SWITCH RECOMBINATION; CYTIDINE DEAMINASE AID; CELL-CYCLE ARREST; ATAXIA-TELANGIECTASIA; B-CELLS; GENOMIC INSTABILITY; IONIZING-RADIATION; SOMATIC HYPERMUTATION; V(D)J RECOMBINATION AB The DNA double-strand break (DSB) repair protein DNA-PKcs and the signal transducer ATM are both activated by DNA breaks and phosphorylate similar substrates in vitro, yet appear to have distinct functions in vivo. Here, we show that ATM and DNA-PKcs have overlapping functions in lymphocytes. Ablation of both kinase activities in cells undergoing immunoglobulin class switch recombination leads to a compound defect in switching and a synergistic increase in chromosomal fragmentation, DNA insertions, and translocations due to aberrant processing of DSBs. These abnormalities are attributed to a compound deficiency in phosphorylation of key proteins required for DNA repair, class switching, and cell death. Notably, both kinases are required for normal levels of p53 phosphorylation in B and T cells and p53-dependent apoptosis. Our experiments reveal a DNA-PKcs-dependent pathway that regulates DNA repair and activation of p53 in the absence of ATM. C1 [Callen, Elsa; Wong, Nancy; Chen, Hua-Tang; Difilippantonio, Simone; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Zha, Shan; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zha, Shan; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Jankovic, Mila; Di Virgilio, Michela; Heidkamp, Gordon; Nussenzweig, Michel] Howard Hughes Med Inst, New York, NY 10065 USA. [Jankovic, Mila; Di Virgilio, Michela; Heidkamp, Gordon; Nussenzweig, Michel] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov; nussen@mall.rockefeller.edu FU NIH; National Cancer Institute; Center for Cancer Research FX We thank Junjie Chen and Anthony Wynshaw-Boris for mice; L. Stapelton for chromosome painting probes; G. Smith for small molecule inhibitors; Jeremy Daniel, Davide Robbiani, Oscar Femandez-Capetillo, and Yair Dorsett for comments on the manuscript; and Rafael Casellas for advice on ShRNA. A.N. is supported by the Intramural Research program of the NIH, National Cancer Institute, Center for Cancer Research. F.W.A. is supported by grants from the NIH. F.W.A. is a Howard Hughes Institute Investigator. M.C.N. is supported by grants from the NIH. M.C.N. is a Howard Hughes Institute Investigator. NR 87 TC 85 Z9 87 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY 15 PY 2009 VL 34 IS 3 BP 285 EP 297 DI 10.1016/j.molcel.2009.04.025 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 446TP UT WOS:000266144400004 PM 19450527 ER PT J AU Zabetian, CP Yamamoto, M Lopez, AN Ujike, H Mata, IF Izumi, Y Kaji, R Maruyama, H Morino, H Oda, M Hutter, CM Edwards, KL Schellenberg, GD Tsuang, DW Yearout, D Larson, EB Kawakami, H AF Zabetian, Cyrus P. Yamamoto, Mitsutoshi Lopez, Alexis N. Ujike, Hiroshi Mata, Ignacio F. Izumi, Yuishin Kaji, Ryuji Maruyama, Hirofumi Morino, Hiroyuki Oda, Masaya Hutter, Carolyn M. Edwards, Karen L. Schellenberg, Gerard D. Tsuang, Debby W. Yearout, Dora Larson, Eric B. Kawakami, Hideshi TI LRRK2 Mutations and Risk Variants in Japanese Patients with Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE mutation; polymorphism; Parkinson ID GLY2385ARG VARIANT; ALPHA-SYNUCLEIN; LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; ASHKENAZI JEWS; POPULATION; HAPLOTYPE; CHINESE; G2019S; PREVALENCE AB Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic determinant of Parkinson's disease (PD) in European-derived populations, but far less is known about LRRK2 mutations and susceptibility alleles in Asians. To address this issue, we sequenced the LRRK2 coding region in 36 patients with familial PD, then genotyped variants of interest in an additional 595 PD cases and 1,641 controls who were all of Japanese ancestry. We also performed a meta-analysis of studies on G2385R, a polymorphism previously reported to associate with PD. One pathogenic (G20195) and one putative pathogenic (R1067Q) mutation were each observed in two patients with sporadic PD. The overall mutation frequence among patients was 0.6% G2385R was highly associated with PD under a dominant model in our dataset (adjusted OR, 1.83; 95% CI, 1.31-2.54; P = 3.3 x 10(-4)) and similar results were seen in the meta-analysis (summary OR assuming fixed effects, 2.55; 95% CI, 2.10-3.10).G2385R represents the first consistently replicated common PD susceptibility variant in a non-European population and its effect size is substantially greater than that reported for other well-validated genetic risk factors for the disease. However, LRRK2 mutations appear to be rare among Japanese patients with PD. (C) 2009 Movement Disorder Society C1 [Zabetian, Cyrus P.; Lopez, Alexis N.; Mata, Ignacio F.; Schellenberg, Gerard D.; Yearout, Dora] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. [Zabetian, Cyrus P.; Lopez, Alexis N.; Mata, Ignacio F.; Schellenberg, Gerard D.; Yearout, Dora] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, NW Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Zabetian, Cyrus P.; Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Yamamoto, Mitsutoshi] Kagawa Prefectural Cent Hosp, Dept Neurol, Takamatsu, Kagawa, Japan. [Ujike, Hiroshi] Okayama Univ, Dept Neuropsychiat, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan. [Izumi, Yuishin; Kaji, Ryuji] Univ Tokushima, Dept Clin Neurosci, Inst Hlth Biosci, Grad Sch, Tokushima 770, Japan. [Maruyama, Hirofumi; Morino, Hiroyuki; Kawakami, Hideshi] Hiroshima Univ, Dept Epidemiol, Res Inst Radiat Biol & Med, Hiroshima, Japan. [Oda, Masaya] Sumitomo Hosp, Dept Neurol, Osaka, Japan. [Hutter, Carolyn M.; Edwards, Karen L.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Schellenberg, Gerard D.; Larson, Eric B.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Schellenberg, Gerard D.] Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. [Tsuang, Debby W.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S 182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetien@u.washington.edu RI Maruyama, Hirofumi/B-9333-2011; Kawakami, Hideshi/A-2086-2009; Morino, Hiroyuki/H-9583-2013; Tsuang, Debby/L-7234-2016; OI Zabetian, Cyrus/0000-0002-7739-4306; Kawakami, Hideshi/0000-0002-1405-0901; Morino, Hiroyuki/0000-0002-5190-3547; Tsuang, Debby/0000-0002-4716-1894; Fernandez Mata, Ignacio/0000-0003-1198-0633 FU American Parkinson Disease Association; National Institutes of Health; Institute Of Neurological Disorders and Stroke. [K08 NS044138]; Department of Veterans Affairs; Smoking Research Foundation FX This work was Supported by the American Parkinson Disease Association (Research Grant to Dr Zabetian), National Institutes of Health (Nationat Institute Of Neurological Disorders and Stroke. grant K08 NS044138, to Dr Zabetian), Department of Veterans Affairs (Merit Review Award to Dr Zabetian), Smoking Research Foundation (Grant for Biomedical Research to Dr. Kawakami), and the Veterans Integrated Service Network 20 Geriatric. Mental Illness, and Parkinson's Disease Research Education and Clinical Centers. We thank the individuals who participated in the study. Positive controls for TaqMan assays were provided by Eng-King Tan, MD (R1067Q and IVS33+6T -> A) and Owen Ross, PhD (R1628P). NR 37 TC 32 Z9 33 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY 15 PY 2009 VL 24 IS 7 BP 1034 EP 1041 DI 10.1002/mds.22514 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 453NQ UT WOS:000266617900012 PM 19343804 ER PT J AU Jovicich, J Czanner, S Han, X Salat, D van der Kouwe, A Quinn, B Pacheco, J Albert, M Killiany, R Blacker, D Maguire, P Rosas, D Makris, N Gollub, R Dale, A Dickerson, BC Fischl, B AF Jovicich, Jorge Czanner, Silvester Han, Xiao Salat, David van der Kouwe, Andre Quinn, Brian Pacheco, Jenni Albert, Marilyn Killiany, Ronald Blacker, Deborah Maguire, Paul Rosas, Diana Makris, Nikos Gollub, Randy Dale, Anders Dickerson, Bradford C. Fischl, Bruce TI MRI-derived measurements of human subcortical, ventricular and intracranial brain volumes: Reliability effects of scan sessions, acquisition sequences, data analyses, scanner upgrade, scanner vendors and field strengths SO NEUROIMAGE LA English DT Article DE Subcortical brain volumes; Reproducibility; Reliability; Structural MRI; Cerebral cortex; Morphology ID PRECLINICAL HUNTINGTONS-DISEASE; TENSOR-BASED MORPHOMETRY; VOXEL-BASED MORPHOMETRY; STRUCTURAL NEUROPATHOLOGY; CEREBRAL ATROPHY; SEGMENTATION; PROGRESSION; SCHIZOPHRENIA; DISORDER; DEMENTIA AB Automated MRI-derived measurements of in-vivo human brain volumes provide novel insights into normal and abnormal neuroanatomy, but little is known about measurement reliability. Here we assess the impact of image acquisition variables (scan session, MRI sequence, scanner upgrade, vendor and field strengths), FreeSurfer segmentation pre-processing variables (image averaging, B1 field inhomogeneity correction) and segmentation analysis variables (probabilistic atlas) on resultant image segmentation volumes from older (n = 15, mean age 69.5) and younger (both n = 5, mean ages 34 and 36.5) healthy subjects. The variability between hippocampal, thalamic, caudate, putamen, lateral ventricular and total intracranial volume measures across sessions on the same scanner on different days is less than 4.3% for the older group and less than 2.3% for the younger group. Within-scanner measurements are remarkably reliable across scan sessions, being minimally affected by averaging of multiple acquisitions, B1 correction, acquisition sequence (MPRAGE vs. multi-echo-FLASH), major scanner upgrades (Sonata-Avanto, Trio-TrioTIM), and segmentation atlas (MPRAGE or multi-echo-FLASH). Volume measurements across platforms (Siemens Sonata vs. GE Signa) and field strengths (1.5 T vs. 3 T) result in a volume difference bias but with a comparable variance as that measured within-scanner, implying that multi-site studies may not necessarily require a much larger sample to detect a specific effect. These results suggest that volumes derived from automated segmentation of T1-weighted structural images are reliable measures within the same scanner platform, even after upgrades; however, combining data across platform and across field-strength introduces a bias that should be considered in the design of multi-site studies, such as clinical drug trials. The results derived from the young groups (scanner upgrade effects and B1 inhomogeneity correction effects) should be considered as preliminary and in need for further validation with a larger dataset. (C) 2009 Elsevier Inc. All rights reserved. C1 [Jovicich, Jorge] Univ Trent, Dept Cognit & Educ Sci, Ctr Mind Brain Sci, Trento, Italy. [Czanner, Silvester] Univ Warwick, Sch Engn, Warwick Mfg Grp, Coventry CV4 7AL, W Midlands, England. [Han, Xiao] CMS Inc, St Louis, MO USA. [Salat, David; van der Kouwe, Andre; Quinn, Brian; Pacheco, Jenni; Rosas, Diana; Makris, Nikos; Gollub, Randy; Fischl, Bruce] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Rosas, Diana; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Salat, David; van der Kouwe, Andre; Quinn, Brian; Pacheco, Jenni; Blacker, Deborah; Rosas, Diana; Makris, Nikos; Gollub, Randy; Dickerson, Bradford C.; Fischl, Bruce] Harvard Univ, Sch Med, Boston, MA USA. [Blacker, Deborah; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Boston, MA 02114 USA. [Albert, Marilyn] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21218 USA. [Killiany, Ronald] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02215 USA. [Maguire, Paul] Pfizer Global Res & Dev, Groton, CT USA. [Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. [Dale, Anders] Univ Calif San Diego, La Jolla, CA 92093 USA. [Dickerson, Bradford C.] Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Fischl, Bruce] MIT, CSAIL HST, Cambridge, MA 02139 USA. RP Jovicich, J (reprint author), Univ Trent, Dept Cognit & Educ Sci, Ctr Mind Brain Sci, Trento, Italy. EM jorge.jovicich@unitn.it RI Jovicich, Jorge/D-2293-2010; Dale, Anders/A-5180-2010; OI Maguire, Ralph/0000-0003-3937-6622; Gollub, Randy L./0000-0002-9434-4044; Jovicich, Jorge/0000-0001-9504-7503 FU NCRR NIH HHS [U24 RR021382, P41 RR014075, P41 RR014075-04, P41-RR14075, R01 RR016594, R01 RR016594-01A1, R01-RR16594-01A1, U24 RR021382-05, U24RR021382]; NIA NIH HHS [K23 AG022509, K23 AG022509-01, K23-AG22509, P01 AG004953, P01 AG004953-140004, P01-AG04953, R01 AG029411, R01 AG029411-02, R21 AG029840, R21 AG029840-02] NR 62 TC 243 Z9 244 U1 3 U2 27 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 15 PY 2009 VL 46 IS 1 BP 177 EP 192 DI 10.1016/j.neuroimage.2009.02.010 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 440TY UT WOS:000265723800020 PM 19233293 ER PT J AU Chee, MWL Chen, KHM Zheng, H Chan, KPL Isaac, V Sim, SKY Chuah, LYM Schuchinsky, M Fischl, B Ng, TP AF Chee, Michael W. L. Chen, Karren H. M. Zheng, Hui Chan, Karen P. L. Isaac, Vivian Sim, Sam K. Y. Chuah, Lisa Y. M. Schuchinsky, Maria Fischl, Bruce Ng, Tze Pin TI Cognitive function and brain structure correlations in healthy elderly East Asians SO NEUROIMAGE LA English DT Review DE Cognitive aging; Cohort studies; MRI; Volumetry; Cortical thickness; White matter ID BODY-MASS INDEX; WHITE-MATTER HYPERINTENSITIES; TOTAL INTRACRANIAL VOLUME; PREFRONTAL GRAY-MATTER; ALZHEIMERS-DISEASE; ROTTERDAM SCAN; OLDER-ADULTS; HIPPOCAMPAL VOLUME; RESERVE-HYPOTHESIS; CEREBRAL-RESERVE AB We investigated the effect of age and health variables known to modulate cognitive aging on several measures of cognitive performance and brain volume in a cohort of healthy, non-demented persons of Chinese descent aged between 55 and 86 years. 248 subjects contributed combined neuropsychological, MR imaging, health and socio-demographic information. Speed of processing showed the largest age-related decline. Education and plasma homocysteine levels modulated age-related decline in cognitive performance. Total cerebral volume declined at an annual rate of 0.4%/yr. Gray and white matter volume loss was comparable in magnitude. Regionally, there was relatively greater volume loss in the lateral prefrontal cortex bilaterally, around the primary visual cortex as well as bilateral superior parietal cortices. Speed of processing showed significant positive correlation with gray matter volume in several frontal, parietal and midline occipital regions bilaterally. In spite of differences in diet, lifestyle and culture, these findings are broadly comparable to studies conducted in Caucasian populations and suggest generalizability of processes involved in age-related decline in cognition and brain volume. (C) 2009 Elsevier Inc. All rights reserved. C1 [Chee, Michael W. L.; Chen, Karren H. M.; Zheng, Hui; Chan, Karen P. L.; Isaac, Vivian; Sim, Sam K. Y.; Chuah, Lisa Y. M.; Schuchinsky, Maria] Duke NUS Grad Med Sch Singapore, Cognit Neurosci Lab, Singapore 169611, Singapore. [Fischl, Bruce] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA USA. [Ng, Tze Pin] Natl Univ Singapore, Fac Med, Gerontol Res Programme, Singapore 117548, Singapore. RP Chee, MWL (reprint author), Duke NUS Grad Med Sch Singapore, Cognit Neurosci Lab, 7 Hosp Dr,Block B,01-11, Singapore 169611, Singapore. EM michael.chee@duke-nus.edu.sg RI Isaac, Vivian /B-5581-2017; OI Isaac, Vivian /0000-0003-1525-8090; Chee, Michael/0000-0002-6087-0548 FU Biomedical Research Council, Singapore: BMRC [04/1/36/372]; A*STAR: SRP [R-913-200-004-304] FX Arne Littmann provided proprietary homogeneity correction and gradient distortion correction techniques. Jenni Pacheco provided on-site training for the use of FreeSurfer. Cliff Jack provided valuable advice on manual morphometry and the quality control aspects of this study. This work was supported by the Biomedical Research Council, Singapore: BMRC 04/1/36/372 and A*STAR: SRP R-913-200-004-304. NR 111 TC 45 Z9 46 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 15 PY 2009 VL 46 IS 1 BP 257 EP 269 DI 10.1016/j.neuroimage.2009.01.036 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 440TY UT WOS:000265723800028 PM 19457386 ER PT J AU Schilero, GJ Spungen, AM Bauman, WA Radulovic, M Lesser, M AF Schilero, Gregory J. Spungen, Ann M. Bauman, William A. Radulovic, Miroslav Lesser, Marvin TI Pulmonary function and spinal cord injury SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Review DE Spinal cord injury; Respiratory Function Tests; Obstructive sleep apnea; Tetraplegia ID OBSTRUCTIVE SLEEP-APNEA; INSPIRATORY MUSCLE STRENGTH; POSITIVE AIRWAY PRESSURE; RIB CAGE MOTION; MAXIMAL EXPIRATORY PRESSURE; LOWER RESPIRATORY-TRACT; FORCED VITAL CAPACITY; TETRAPLEGIC PATIENTS; CERVICAL CORD; ELECTRICAL-STIMULATION AB Injury to the cervical and upper thoracic spinal cord disrupts function of inspiratory and expiratory muscles, as reflected by reduction in spirometric and lung volume parameters and static mouth pressures. In association, subjects with tetraplegia have decreased chest wall and lung compliance, increased abdominal wall compliance, and rib cage stiffness with paradoxical chest wall movements, all of which contribute to an increase in the work of breathing. Expiratory muscle function is more compromised than inspiratory muscle function among subjects with tetraplegia and high paraplegia, which can result in ineffective cough and propensity to mucus retention and atelectasis. Subjects with tetraplegia also demonstrate heightened vagal activity with reduction in baseline airway caliber, findings attributed to loss of sympathetic innervation to the lungs. Significant increase in airway caliber following inhalation of ipratropium bromide, an anticholinergic agent, suggests that reduction in airway caliber is not due to acquired airway fibrosis stemming from repeated infections or to abnormal hysteresis secondary to chronic inability of subjects to inhale to predicted total lung capacity. Reduced baseline airway caliber possibly explains why subjects with tetraplegia exhibit airway hyperresponsiveness to methacholine and ultrasonically nebulized distilled water. While it has been well demonstrated that bilateral phrenic nerve pacing or stimulation through intramuscular diaphragmatic electrodes improves inspiratory muscle function, it remains unclear if inspiratory muscle training improves pulmonary function. Recent findings suggest that expiratory muscle training, electrical stimulation of expiratory muscles and administration of a long-acting beta(2)-agonist (salmeterol) improve physiological parameters and cough. It is unknown if baseline bronchoconstriction in tetraplegia contributes to respiratory symptoms, of if the chronic administration of a bronchodilator reduces the work of breathing and/or improves respiratory symptoms. Less is known regarding the benefits of treatment of obstructive sleep apnea, despite evidence indicating that the prevalence of this condition in persons with tetraplegia is far greater than that encountered in able-bodied individuals. Published by Elsevier B.V. C1 [Schilero, Gregory J.; Spungen, Ann M.; Bauman, William A.; Radulovic, Miroslav; Lesser, Marvin] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Rehabil Res & Dev Ctr, Bronx, NY 10468 USA. [Schilero, Gregory J.; Spungen, Ann M.; Bauman, William A.; Radulovic, Miroslav] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Spungen, Ann M.; Bauman, William A.] James J Peters VA Med Ctr, Spinal Cord Injury Serv, Bronx, NY 10468 USA. [Schilero, Gregory J.; Spungen, Ann M.; Bauman, William A.; Radulovic, Miroslav] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Spungen, Ann M.; Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. RP Schilero, GJ (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Rehabil Res & Dev Ctr, Rm 1 E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM greg.schilero@va.gov NR 206 TC 58 Z9 64 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD MAY 15 PY 2009 VL 166 IS 3 BP 129 EP 141 DI 10.1016/j.resp.2009.04.002 PG 13 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 455HP UT WOS:000266749600001 PM 19442929 ER PT J AU Tahiliani, M Koh, KP Shen, YH Pastor, WA Bandukwala, H Brudno, Y Agarwal, S Iyer, LM Liu, DR Aravind, L Rao, A AF Tahiliani, Mamta Koh, Kian Peng Shen, Yinghua Pastor, William A. Bandukwala, Hozefa Brudno, Yevgeny Agarwal, Suneet Iyer, Lakshminarayan M. Liu, David R. Aravind, L. Rao, Anjana TI Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1 SO SCIENCE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; GLYCOSYLASE ACTIVITY; CXXC DOMAIN; BASE-J; DEMETHYLATION; CYTOSINE; METHYLATION; PROTEIN; METHYLTRANSFERASE; T(10/11)(Q22,Q23) AB DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development. In a computational search for enzymes that could modify 5-methylcytosine (5mC), we identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. We show here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro. hmC is present in the genome of mouse embryonic stem cells, and hmC levels decrease upon RNA interference-mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC. C1 [Shen, Yinghua; Brudno, Yevgeny; Liu, David R.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. [Shen, Yinghua; Brudno, Yevgeny; Liu, David R.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Tahiliani, Mamta; Koh, Kian Peng; Pastor, William A.; Bandukwala, Hozefa; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Tahiliani, Mamta; Koh, Kian Peng; Pastor, William A.; Bandukwala, Hozefa; Rao, Anjana] Immune Dis Inst, Boston, MA 02115 USA. [Agarwal, Suneet] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Agarwal, Suneet] Dana Farber Canc Inst, Boston, MA 02115 USA. [Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Liu, DR (reprint author), Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. EM drliu@fas.harvard.edu; aravind@ncbi.nlm.nih.gov; arao@idi.harvard.edu RI Waha, Andreas/J-2950-2014 FU NIH [AI44432, K08 HL089150]; a Scholar Award from the Juvenile Diabetes Research Foundation; Harvard Stem Cell Institute [Seed]; Howard Hughes Medical Institute; NIH/NIGMS [R01GM065865]; American Heart Association postdoctoral fellowship; National Library of Medicine, NIH; Lady Tata Memorial postdoctoral fellowship; NSF Graduate Fellowships; Department of Defense graduate fellowship FX We thank K. Kreuzer for the gift of the T4 phage and E. coli ER1656 and CR63; Charles Richardson, Udi Qimron, and Ben Beauchamp for advice and assistance in culturing T4 phage; Melissa Call for advice on production of recombinant proteins in insect cells; and Patrick Hogan for many helpful discussions. This work was supported by NIH grant AI44432, a Scholar Award from the Juvenile Diabetes Research Foundation, and a Seed grant from the Harvard Stem Cell Institute (to A.R.); Howard Hughes Medical Institute and NIH/NIGMS (R01GM065865) funding (to D.R.L.); an American Heart Association postdoctoral fellowship (to K.P.K.); intramural funds of the National Library of Medicine, NIH (to L.A. and L.M.I.); a Lady Tata Memorial postdoctoral fellowship (to H.B.); NIH award K08 HL089150 (to S.A.); NSF Graduate Fellowships (to W.A.P. and Y.B.); and a Department of Defense graduate fellowship (to W.A.P.). NR 33 TC 2102 Z9 2172 U1 37 U2 317 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 15 PY 2009 VL 324 IS 5929 BP 930 EP 935 DI 10.1126/science.1170116 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 445KD UT WOS:000266048800037 PM 19372391 ER PT J AU Atlas, SJ AF Atlas, Steven J. TI Point of View SO SPINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Atlas, SJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM satlas@partners.org NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAY 15 PY 2009 VL 34 IS 11 BP 1227 EP 1227 DI 10.1097/BRS.0b013e31819f29e5 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA V17ZX UT WOS:000207976200005 ER PT J AU Zhou, XH Hu, N Hu, GZ Root, M AF Zhou, Xiao-Hua Hu, Nan Hu, Guizhou Root, Martin TI Synthesis analysis of regression models with a continuous outcome SO STATISTICS IN MEDICINE LA English DT Article DE synthesis analysis; meta-analysis; linear models ID DISEASE AB To estimate the multivariate regression model from multiple individual studies, it would be challenging to obtain results if the input from individual studies only provide univariate or incomplete multivariate regression information. Samsa et al. (J. Biomed. Biotechnol. 2005; 2:113-123) proposed a simple method to combine coefficients from univariate linear regression models into a multivariate linear regression model, a method known as synthesis analysis. However, the validity of this method relies on the normality assumption of the data, and it does not provide variance estimates. In this paper we propose a new synthesis method that improves on the existing synthesis method by eliminating the normality assumption, reducing bias, and allowing for the variance estimation of the estimated parameters. Copyright (c) 2009 John Wiley & Sons, Ltd. C1 [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA. [Zhou, Xiao-Hua; Hu, Nan] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Hu, Guizhou; Root, Martin] BioSignia Inc, Durham, NC 27713 USA. RP Zhou, XH (reprint author), VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA. EM azhou@u.washington.edu FU NSFC [30728019] FX We would like to thank Vicki Ding and Hua Chen for their help in preparing this manuscript. Xiao-Hua Zhou, PhD, is presently a Core Investigator and Biostatistics Unit Director at the Northwest HSR&D Center of Excellence, Department of Veterans Affairs Medical Center, Seattle, WA. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. This study has been partially supported by NSFC 30728019. NR 6 TC 5 Z9 6 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 15 PY 2009 VL 28 IS 11 BP 1620 EP 1635 DI 10.1002/sim.3563 PG 16 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 446TC UT WOS:000266143100006 PM 19326397 ER PT J AU Griesemer, AD Okumi, M Shimizu, A Moran, S Ishikawa, Y Iorio, J Arn, JS Yamada, K AF Griesemer, Adam D. Okumi, Masayoshi Shimizu, Akira Moran, Shannon Ishikawa, Yoshinori Iorio, Justin Arn, J. Scott Yamada, Kazuhiko TI Upregulation of CD59: Potential Mechanism of Accommodation in a Large Animal Model SO TRANSPLANTATION LA English DT Article DE Accommodation; CD59; Swine; Gal ID KNOCKOUT MINIATURE SWINE; KIDNEY-TRANSPLANTATION; IMMUNOAFFINITY COLUMN; ENDOTHELIAL-CELLS; RENAL-ALLOGRAFTS; NUCLEAR TRANSFER; HUMAN-COMPLEMENT; TRANSGENIC PIG; IN-VITRO; EXPRESSION AB Background. Survival of ABO-mismatched kidneys with stable renal function despite the persistence of anti-ABO antibodies is called accommodation. The mechanism of accommodation is unclear, but may involve complement regulatory proteins such as CD59. The development of alpha-1,3-galactosyltransferase knock-out (GalT-KO) swine that produce anti-Gal antibodies provides a large animal model capable of determining the role of complement regulatory proteins in accommodation. Methods. ELISA and antibody fluorescence-activated cell sorting were used to examine the rate of anti-Gal antibody expression as a function of age. Major histocompatibility complex-matched kidneys were transplanted from Gal-positive NIGH miniature swine to NIGH GalT-KO swine with systemic immunosuppression. One recipient underwent adsorbtion of anti-Gal antibodies before transplantation. Graft survival, antibody, and complement deposition patterns and CD59 expression were determined. Results. Three animals rejected Gal-positive kidneys by humoral mechanisms. One animal with low titers of anti-Gal antibody displayed spontaneous accommodation and the animal that was treated with antibody adsorbtion also displayed accommodation. Rejected grafts had deposition of IgM, IgG, C3, and C5b-9 with low expression of CD59, whereas accommodated grafts had low deposition of C5b-9 and high expression of CD59. Retransplantation of one accommodated graft to a naive GalT-KO animal confirmed that changes in the graft were responsible for the lack of C5b-9 deposition. Conclusion. GalT-KO miniature swine produce anti-Gal antibodies and titers increase with age. These anti-Gal antibodies can cause rejection of major histocompatibility complex-matched kidneys unless accommodation occurs. CD59 up-regulation seems to be involved in the mechanism of accommodation by preventing the formation of the membrane attack complex (MAC) on the accommodated graft. C1 [Yamada, Kazuhiko] Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Med Sch,MGH E, Head Organ Transplantat Tolerance & Xenotransplan, Boston, MA 02129 USA. [Shimizu, Akira] Nippon Med Sch, Dept Pathol, Tokyo 113, Japan. RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Med Sch,MGH E, Head Organ Transplantat Tolerance & Xenotransplan, 13th St,CNY 149,9019, Boston, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu FU NIH Program Project [5PO1-A145897]; Japanese Society for the Promotion of Science [A-19209043]; American Society of Transplantation/Juvende Diabetes Research Foundation Fellowship FX This work was supported by the NIH Program Project 5PO1-A145897 (Project 1) and the Japanese Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A-19209043) and by the American Society of Transplantation/Juvende Diabetes Research Foundation Fellowship (A.G.). NR 41 TC 16 Z9 17 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 2009 VL 87 IS 9 BP 1308 EP 1317 DI 10.1097/TP.0b013e3181a19afc PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 445JW UT WOS:000266048100009 PM 19424030 ER PT J AU Sykes, M AF Sykes, Megan TI Mechanisms of Transplantation Tolerance in Animals and Humans SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 8th Beaune Seminar in Transplantation Research CY JUN 12-13, 2008 CL Beaune, FRANCE DE Tolerance; Thymus; Chimerism; T-cells ID BONE-MARROW-TRANSPLANTATION; T-CELL TOLERANCE; REFRACTORY HEMATOLOGIC MALIGNANCIES; MIXED CHIMERISM; MEDIATED ALLORESISTANCE; COSTIMULATORY BLOCKADE; MONOCLONAL-ANTIBODY; ALLOGENEIC MARROW; ALLOREACTIVE CD8; HOST-DISEASE AB Donor-specific immune tolerance would avoid the toxicities of chronic immunosuppressive therapies while preventing graft rejection. Hematopoietic cell transplantation has shown preliminary success for intentional tolerance induction in pilot clinical trials. The mechanisms of tolerance in these trials and the animal studies leading up to them are discussed. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv,Transplantat Biol Res Ctr,Bone Marrow T, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv,Transplantat Biol Res Ctr,Bone Marrow T, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NCI NIH HHS [P01 CA111519, P01 CA111519-01A2, P01 CA111519-01A20001, P01 CA111519-02, P01 CA111519-020001, P01 CA111519-03, P01 CA111519-030001, R01 CA079989, R01 CA079989-06, R01 CA079989-07, R01 CA079989-08, R01 CA079989-09]; NHLBI NIH HHS [R01 HL49915, P01 HL018646, P01 HL018646-270014, P01 HL018646-280014, P01 HL018646-290014, P01 HL018646-300014, P01 HL18646, R01 HL049915, R01 HL049915-09, R01 HL049915-10, R01 HL049915-11, R01 HL049915-12, R01 HL049915-13A1, P01 HL018646-26A10014] NR 28 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 2009 VL 87 IS 9 BP S67 EP S69 DI 10.1097/TP.0b013e3181a2a6b8 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 445JX UT WOS:000266048200012 PM 19424011 ER PT J AU Carson, KR Evens, AM Richey, EA Habermann, TM Focosi, D Seymour, JF Laubach, J Bawn, SD Gordon, LI Winter, JN Furman, RR Vose, JM Zelenetz, AD Mamtani, R Raisch, DW Dorshimer, GW Rosen, ST Muro, K Gottardi-Littell, NR Talley, RL Sartor, O Green, D Major, EO Bennett, CL AF Carson, Kenneth R. Evens, Andrew M. Richey, Elizabeth A. Habermann, Thomas M. Focosi, Daniele Seymour, John F. Laubach, Jacob Bawn, Susie D. Gordon, Leo I. Winter, Jane N. Furman, Richard R. Vose, Julie M. Zelenetz, Andrew D. Mamtani, Ronac Raisch, Dennis W. Dorshimer, Gary W. Rosen, Steven T. Muro, Kenji Gottardi-Littell, Numa R. Talley, Robert L. Sartor, Oliver Green, David Major, Eugene O. Bennett, Charles L. TI Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project SO BLOOD LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 30-JUN 03, 2008 CL Chicago, IL SP Amer Soc Clin Oncol ID B-CELL LYMPHOMA; IDIOPATHIC THROMBOCYTOPENIC PURPURA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHEMOTHERAPY PLUS RITUXIMAB; MULTIPLE-SCLEROSIS PATIENTS; OF-THE-LITERATURE; JC VIRUS VIREMIA; ANTIBODY NATALIZUMAB; FOLLICULAR LYMPHOMA; INFECTED PATIENTS AB Rituximab improves outcomes for persons with lymphoproliferative disorders and is increasingly used to treat immune-mediated illnesses. Recent reports describe 2 patients with systemic lupus erythematosus and 1 with rheumatoid arthritis who developed progressive multifocal leukoencephalopathy (PML) after rituximab treatment. We reviewed PML case descriptions among patients treated with rituximab from the Food and Drug Administration, the manufacturer, physicians, and a literature review from 1997 to 2008. Overall, 52 patients with lymphoproliferative disorders, 2 patients with systemic lupus erythematosus, 1 patient with rheumatoid arthritis, 1 patient with an idiopathic autoimmune pancytopenia, and 1 patient with immune thrombocytopenia developed PML after treatment with rituximab and other agents. Other treatments included hematopoietic stem cell transplantation (7 patients), purine analogs (26 patients), or alkylating agents (39 patients). One patient with an autoimmune hemolytic anemia developed PML after treatment with corticosteroids and rituximab, and 1 patient with an autoimmune pancytopenia developed PML after treatment with corticosteroids, azathioprine, and rituximab. Median time from last rituximab dose to PML diagnosis was 5.5 months. Median time to death after PML diagnosis was 2.0 months. The case-fatality rate was 90%. Awareness is needed of the potential for PML among rituximab-treated persons. (Blood. 2009;113:4834-4840) C1 [Evens, Andrew M.; Richey, Elizabeth A.; Gordon, Leo I.; Winter, Jane N.; Rosen, Steven T.; Green, David; Bennett, Charles L.] Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA. [Carson, Kenneth R.] Washington Univ, Sch Med, Siteman Comprehens Canc Ctr, St Louis, MO USA. [Evens, Andrew M.; Gordon, Leo I.; Winter, Jane N.; Rosen, Steven T.; Green, David; Bennett, Charles L.] Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. [Habermann, Thomas M.] Mayo Clin, Coll Med, Dept Hematol, Rochester, MN USA. [Focosi, Daniele] Univ Pisa, Div Hematol, Pisa, Italy. [Seymour, John F.] Peter MacCallum Canc Ctr, Div Haematol & Med Oncol, Melbourne, Australia. [Laubach, Jacob] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bawn, Susie D.] Stanford Univ, Sch Med, Div Hematol Oncol, Stanford, CA 94305 USA. [Furman, Richard R.; Zelenetz, Andrew D.; Mamtani, Ronac] New York Presbyterian Hosp, Cornell Med Ctr, Div Hematol Oncol, New York, NY USA. [Vose, Julie M.] Univ Nebraska, Med Ctr, Hematol Oncol Sect, Omaha, NE USA. [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, Div Hematol Oncol, New York, NY 10021 USA. [Raisch, Dennis W.] Univ New Mexico, Vet Adm Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, Albuquerque, NM 87131 USA. [Dorshimer, Gary W.] Univ Penn Hlth Syst, Penn Hosp, Philadelphia, PA USA. [Muro, Kenji] Northwestern Univ, Dept Neurol Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Gottardi-Littell, Numa R.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. [Talley, Robert L.] Kansas City Canc Ctr, Kansas City, MO USA. [Sartor, Oliver] Tulane Med Sch, New Orleans, LA USA. [Major, Eugene O.] Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, Bethesda, MD USA. [Bennett, Charles L.] Jesse Brown VAMC, Vet Adm Ctr Management Complex Chron Condit, Chicago, IL USA. RP Bennett, CL (reprint author), Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, 710 N Fairbanks Ct,Olson Pavil,Suite 8-250, Chicago, IL 60611 USA. EM cbenne@northwestern.edu OI Zelenetz, Andrew/0000-0003-1403-6883; Focosi, Daniele/0000-0001-8811-195X; Gordon, Leo/0000-0003-1666-7064 FU NCI NIH HHS [1R01 CA125077-01A1, R01 CA125077] NR 68 TC 465 Z9 475 U1 9 U2 21 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 14 PY 2009 VL 113 IS 20 BP 4834 EP 4840 DI 10.1182/blood-2008-10-186999 PG 7 WC Hematology SC Hematology GA 445ZT UT WOS:000266090700007 PM 19264918 ER PT J AU Hiruma, Y Honjo, T Jelinek, DF Windle, JJ Shin, J Roodman, GD Kurihara, N AF Hiruma, Yuko Honjo, Tadashi Jelinek, Diane F. Windle, Jolene J. Shin, Jaekyoon Roodman, G. David Kurihara, Noriyoshi TI Increased signaling through p62 in the marrow microenvironment increases myeloma cell growth and osteoclast formation SO BLOOD LA English DT Article ID HUMAN MULTIPLE-MYELOMA; KAPPA-B LIGAND; STROMAL CELLS; BONE MICROENVIRONMENT; RECEPTOR ACTIVATOR; PROGENITOR CELLS; DRUG-RESISTANCE; PAGETS-DISEASE; IN-VITRO; ADHESION AB Adhesive interactions between multiple myeloma ( MM) cells and marrow stromal cells activate multiple signaling pathways including nuclear factor kappa B (NF-kappa B), p38 mitogen-activated protein kinase (MAPK), and Jun N-terminal kinase (JNK) in stromal cells, which promote tumor growth and bone destruction. Sequesto-some-1 (p62), an adapter protein that has no intrinsic enzymatic activity, serves as a platform to facilitate formation of signaling complexes for these pathways. Therefore, we determined if targeting only p62 would inhibit multiple signaling pathways activated in the MM microenvironment and thereby decrease MM cell growth and osteoclast formation. Signaling through NF-kappa B and p38 MAPK was increased in primary stromal cells from MM patients. Increased interleukin-6 (IL-6) production by MM stromal cells was p38 MAPK-dependent while increased vascular cell adhesion molecule-1 (VCAM-1) expression was NF-kappa B-dependent. Knocking-down p62 in patient-derived stromal cells significantly decreased protein kinase C zeta(PKC zeta), VCAM-1, and IL-6 levels as well as decreased stromal cell support of MM cell growth. Similarly, marrow stromal cells from p62(-/-) mice produced much lower levels of IL-6, tumor necrosis factor-alpha (TNF-alpha), and receptor activator of NF-kappa B ligand (RANKL) and supported MM cell growth and osteoclast formation to a much lower extent than normal cells. Thus, p62 is an attractive therapeutic target for MM. (Blood. 2009;113:4894-4902) C1 [Hiruma, Yuko; Honjo, Tadashi; Roodman, G. David; Kurihara, Noriyoshi] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Jelinek, Diane F.] Mayo Clin, Dept Immunol, Rochester, MN USA. [Windle, Jolene J.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Shin, Jaekyoon] Sungkyunkwan Univ, Sch Med, Suwon, South Korea. RP Kurihara, N (reprint author), VA Pittsburgh Healthcare Syst, Res & Dev 151U, Univ Dr C,Rm 2E-115, Pittsburgh, PA 15240 USA. EM Kuriharan@upmc.edu OI Windle, Jolene/0000-0001-6690-385X FU Multiple Myeloma Research Foundation grant; VA Merit Review grant; National Institutes of Health [R01 AR053537-02] FX We thank Dr Deborah Galson for reading the manuscript and her constructive suggestions.; This work was supported by a Multiple Myeloma Research Foundation grant, a VA Merit Review grant, and by research funds from the National Institutes of Health (NIH; grant no. R01 AR053537-02). The materials are the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System, Research and Development. NR 37 TC 25 Z9 25 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 14 PY 2009 VL 113 IS 20 BP 4894 EP 4902 DI 10.1182/blood-2008-08-173948 PG 9 WC Hematology SC Hematology GA 445ZT UT WOS:000266090700014 PM 19282458 ER PT J AU Szostak, JW AF Szostak, Jack W. TI ORIGINS OF LIFE Systems chemistry on early Earth SO NATURE LA English DT Editorial Material C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu NR 4 TC 49 Z9 50 U1 5 U2 56 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 14 PY 2009 VL 459 IS 7244 BP 171 EP 172 DI 10.1038/459171a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 445FR UT WOS:000266036100021 PM 19444196 ER PT J AU Kelly, JX Smilkstein, MJ Brun, R Wittlin, S Cooper, RA Lane, KD Janowsky, A Johnson, RA Dodean, RA Winter, R Hinrichs, DJ Riscoe, MK AF Kelly, Jane X. Smilkstein, Martin J. Brun, Reto Wittlin, Sergio Cooper, Roland A. Lane, Kristin D. Janowsky, Aaron Johnson, Robert A. Dodean, Rozalia A. Winter, Rolf Hinrichs, David J. Riscoe, Michael K. TI Discovery of dual function acridones as a new antimalarial chemotype SO NATURE LA English DT Article ID CHLOROQUINE RESISTANCE TRANSPORTER; TRANSMEMBRANE PROTEIN PFCRT; PLASMODIUM-FALCIPARUM; DIGESTIVE VACUOLE; BETA-HEMATIN; IN-VITRO; DRUG; MALARIA; MUTATIONS; MECHANISM AB Preventing and delaying the emergence of drug resistance is an essential goal of antimalarial drug development. Monotherapy and highly mutable drug targets have each facilitated resistance, and both are undesirable in effective long-term strategies against multi-drug-resistant malaria. Haem remains an immutable and vulnerable target, because it is not parasite-encoded and its detoxification during haemoglobin degradation, critical to parasite survival, can be subverted by drug-haem interaction as in the case of quinolines and many other drugs(1-5). Here we describe a new antimalarial chemotype that combines the haem-targeting character of acridones, together with a chemosensitizing component that counteracts resistance to quinoline antimalarial drugs. Beyond the essential intrinsic characteristics common to deserving candidate antimalarials ( high potency in vitro against pan-sensitive and multi-drug-resistant Plasmodium falciparum, efficacy and safety in vivo after oral administration, inexpensive synthesis and favourable physicochemical properties), our initial lead, T3.5 (3-chloro-6-(2-diethylamino-ethoxy)-10-(2-diethylamino-ethyl)acridone), demonstrates unique synergistic properties. In addition to 'verapamil-like' chemosensitization to chloroquine and amodiaquine against quinoline-resistant parasites, T3.5 also results in an apparently mechanistically distinct synergism with quinine and with piperaquine. This synergy, evident in both quinoline-sensitive and quinoline-resistant parasites, has been demonstrated both in vitro and in vivo. In summary, this innovative acridone design merges intrinsic potency and resistance-counteracting functions in one molecule, and represents a new strategy to expand, enhance and sustain effective antimalarial drug combinations. C1 [Kelly, Jane X.; Smilkstein, Martin J.; Janowsky, Aaron; Johnson, Robert A.; Dodean, Rozalia A.; Winter, Rolf; Hinrichs, David J.; Riscoe, Michael K.] Portland VA Med Ctr, Portland, OR 97239 USA. [Kelly, Jane X.; Smilkstein, Martin J.; Dodean, Rozalia A.; Winter, Rolf; Riscoe, Michael K.] Portland State Univ, Dept Chem, Portland, OR 97201 USA. [Smilkstein, Martin J.; Janowsky, Aaron; Johnson, Robert A.; Hinrichs, David J.; Riscoe, Michael K.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Brun, Reto; Wittlin, Sergio] Swiss Trop Inst, CH-4002 Basel, Switzerland. [Cooper, Roland A.; Lane, Kristin D.] Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA. RP Kelly, JX (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. EM kellyja@ohsu.edu; riscoem@ohsu.edu FU Merit Review Program of the Department of Veterans Affairs FX We thank D. Kyle for the gift of P. falciparum parasite Tm90-C2B, and the Malaria Research and Reference Resource Center for supplying P. falciparum parasites D6, Dd2 and 7G8. We thank A. P. Waters and C. J. Janse for the donation of GFP- labelled P. berghei strain ANKA. We thank L. Jones- Brando and R. Yolken for the cytotoxicity (HFF) data. We are grateful to A. Cornea for the confocal imaging. We thank K. Liebman, C. Hudson, S. Burgess and D. Peyton for compound characterization. We acknowledge financial support from the Merit Review Program of the Department of Veterans Affairs. United States patent applications have been filed by the US Department of Veterans Affairs to protect the intellectual property described in this report. NR 28 TC 104 Z9 106 U1 2 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 14 PY 2009 VL 459 IS 7244 BP 270 EP 273 DI 10.1038/nature07937 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 445FR UT WOS:000266036100045 PM 19357645 ER PT J AU Muss, HB Berry, DA Cirrincione, CT Theodoulou, M Mauer, AM Kornblith, AB Partridge, AH Dressler, LG Cohen, HJ Becker, HP Kartcheske, PA Wheeler, JD Perez, EA Wolff, AC Gralow, JR Burstein, HJ Mahmood, AA Magrinat, G Parker, BA Hart, RD Grenier, D Norton, L Hudis, CA Winer, EP AF Muss, Hyman B. Berry, Donald A. Cirrincione, Constance T. Theodoulou, Maria Mauer, Ann M. Kornblith, Alice B. Partridge, Ann H. Dressler, Lynn G. Cohen, Harvey J. Becker, Heather P. Kartcheske, Patricia A. Wheeler, Judith D. Perez, Edith A. Wolff, Antonio C. Gralow, Julie R. Burstein, Harold J. Mahmood, Ahmad A. Magrinat, Gutav Parker, Barbara A. Hart, Ronald D. Grenier, Debjani Norton, Larry Hudis, Clifford A. Winer, Eric P. CA CALGB Investigators TI Adjuvant Chemotherapy in Older Women with Early-Stage Breast Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONSENSUS RECOMMENDATIONS; RANDOMIZED-TRIALS; CLINICAL-TRIALS; DOSE-INTENSITY; PHASE-II; THERAPY; SURVIVAL; ONCOLOGY; AGE; CYCLOPHOSPHAMIDE AB BACKGROUND Older women with breast cancer are underrepresented in clinical trials, and data on the effects of adjuvant chemotherapy in such patients are scant. We tested for the noninferiority of capecitabine as compared with standard chemotherapy in women with breast cancer who were 65 years of age or older. METHODS We randomly assigned patients with stage I, II, IIIA, or IIIB breast cancer to standard chemotherapy (either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide plus doxorubicin) or capecitabine. Endocrine therapy was recommended after chemotherapy in patients with hormone-receptor-positive tumors. A Bayesian statistical design was used with a range in sample size from 600 to 1800 patients. The primary end point was relapse-free survival. RESULTS When the 600th patient was enrolled, the probability that, with longer follow-up, capecitabine therapy was highly likely to be inferior to standard chemotherapy met a prescribed level, and enrollment was discontinued. After an additional year of follow-up, the hazard ratio for disease recurrence or death in the capecitabine group was 2.09 (95% confidence interval, 1.38 to 3.17; P<0.001). Patients who were randomly assigned to capecitabine were twice as likely to have a relapse and almost twice as likely to die as patients who were randomly assigned to standard chemotherapy (P = 0.02). At 3 years, the rate of relapse-free survival was 68% in the capecitabine group versus 85% in the standard-chemotherapy group, and the overall survival rate was 86% versus 91%. Two patients in the capecitabine group died of treatment-related complications; as compared with patients receiving capecitabine, twice as many patients receiving standard chemotherapy had moderate-to-severe toxic effects (64% vs. 33%). CONCLUSIONS Standard adjuvant chemotherapy is superior to capecitabine in patients with early-stage breast cancer who are 65 years of age or older. (ClinicalTrials.gov number, NCT00024102.) C1 [Muss, Hyman B.] Univ Vermont, Burlington, VT 05405 USA. [Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cirrincione, Constance T.; Kartcheske, Patricia A.] Duke Univ, Med Ctr, Ctr Stat, CALGB, Durham, NC USA. [Theodoulou, Maria; Norton, Larry; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mauer, Ann M.; Becker, Heather P.] CALGB, Chicago, IL USA. [Kornblith, Alice B.; Partridge, Ann H.; Cohen, Harvey J.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Muss, Hyman B.] Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC 27599 USA. [Perez, Edith A.] N Cent Canc Treatment Grp, Rochester, MN USA. [Wolff, Antonio C.] Eastern Cooperat Oncol Grp, Philadelphia, PA USA. [Gralow, Julie R.] SW Oncol Grp, Ann Arbor, MI USA. [Magrinat, Gutav] SE Canc Control Consortium, Community Clin Oncol Program, Goldsboro, NC USA. [Parker, Barbara A.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Hart, Ronald D.] Mt Sinai Sch Med, New York, NY USA. [Grenier, Debjani] Canadian Canc Soc Res Inst, Toronto, ON, Canada. RP Muss, HB (reprint author), Univ N Carolina, Div Hematol Oncol, 170 Manning Dr,Campus Box 7305,3rd Fl, Chapel Hill, NC 27599 USA. EM hyman.muss@gmail.com OI Wolff, Antonio/0000-0003-3734-1063 FU NCI NIH HHS [U10 CA085850, CA31946, CA33601, U10 CA031946, U10 CA031946-21, U10 CA033601, U10 CA033601-24, U10 CA085850-02, U10CA85850] NR 40 TC 242 Z9 249 U1 0 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 14 PY 2009 VL 360 IS 20 BP 2055 EP 2065 DI 10.1056/NEJMoa0810266 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 444WN UT WOS:000266011200004 PM 19439741 ER PT J AU Kotton, CN Elias, N Delmonico, FL Kradin, RL AF Kotton, Camille N. Elias, Nahel Delmonico, Francis L. Kradin, Richard L. TI A Man with Coma after Cardiac Arrest Intestinal schistosomiasis in a brain-dead organ donor SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LIVER-TRANSPLANTATION; TRANSMISSION; VIRUS; HISTORY; DISEASE; GRAFT C1 [Kotton, Camille N.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Elias, Nahel] Massachusetts Gen Hosp, Dept Transplant Surg, Boston, MA 02114 USA. [Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Delmonico, Francis L.] New England Organ Bank Inc, Newton, MA USA. [Kotton, Camille N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Elias, Nahel; Delmonico, Francis L.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. NR 15 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 14 PY 2009 VL 360 IS 20 BP 2118 EP 2125 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 444WN UT WOS:000266011200012 PM 19439747 ER PT J AU Sarin, H Kanevsky, AS Fung, SH Butman, JA Cox, RW Glen, D Reynolds, R Auh, S AF Sarin, Hemant Kanevsky, Ariel S. Fung, Steve H. Butman, John A. Cox, Robert W. Glen, Daniel Reynolds, Richard Auh, Sungyoung TI Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID CONVERTING-ENZYME-INHIBITION; GADOLINIUM-DTPA COMPLEX; TO-TISSUE TRANSPORT; BLOOD-BRAIN; CEREPORT RMP-7; NITRIC-OXIDE; GD-DTPA; QUANTITATIVE MEASUREMENT; CHEMOTHERAPEUTIC-AGENTS; VASCULAR-PERMEABILITY AB Background: The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas. Methods: Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA), a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1st bolus of Gd-DTPA over the first hour, and then re-imaged with a 2nd bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods. Results: The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine-lysine-bradykinin and labradimil increased the blood half-life of Gd-DTPA sufficiently enough to increase significantly the tumor tissue Gd-DTPA area under the time-concentration curve. Conclusion: Metabolically stable bradykinin B2 receptor agonists, methionine-lysine-bradykinin and labradimil, enhance the transvascular delivery of small chemotherapy drugs across the BBTB of malignant gliomas by increasing the blood half-life of the co-infused drug. The selectivity of the increase in drug delivery into the malignant glioma tissue, but not into normal brain tissue or skeletal muscle tissue, is due to the inherent porous nature of the BBTB of malignant glioma microvasculature. C1 [Sarin, Hemant] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. [Sarin, Hemant; Kanevsky, Ariel S.; Butman, John A.] NIH, Radiol & Imaging Sci Program, Ctr Clin, Bethesda, MD 20892 USA. [Fung, Steve H.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Cox, Robert W.; Glen, Daniel; Reynolds, Richard] NIMH, Bethesda, MD 20892 USA. [Auh, Sungyoung] NINDS, NIH, Bethesda, MD 20892 USA. RP Sarin, H (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. EM sarinh@mail.nih.gov; kanevskya@cc.nih.gov; SFUNG@PARTNERS.ORG; JButmanA@cc.nih.gov; robertcox@mail.nih.gov; glend@mail.nih.gov; reynoldr@mail.nih.gov; auhs@ninds.nih.gov RI Butman, John/A-2694-2008; Butman, John/J-2780-2013; OI Butman, John/0000-0002-1547-9195; Fung, Steve/0000-0002-1177-682X FU National Institute of Biomedical Imaging Bioengineering (NIBIB); Radiology and Imaging Sciences Program (CC) FX This study was funded by the National Institute of Biomedical Imaging Bioengineering (NIBIB) and the Radiology and Imaging Sciences Program (CC). We thank Dr. Matthew Hall for useful discussions. NR 65 TC 7 Z9 7 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD MAY 13 PY 2009 VL 7 AR 33 DI 10.1186/1479-5876-7-33 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 461CA UT WOS:000267240800001 PM 19439100 ER PT J AU Vitalo, A Fricchione, J Casali, M Berdichevsky, Y Hoge, EA Rauch, SL Berthiaume, F Yarmush, ML Benson, H Fricchione, GL Levine, JB AF Vitalo, Antonia Fricchione, Jonathan Casali, Monica Berdichevsky, Yevgeny Hoge, Elizabeth A. Rauch, Scott L. Berthiaume, Francois Yarmush, Martin L. Benson, Herbert Fricchione, Gregory L. Levine, John B. TI Nest Making and Oxytocin Comparably Promote Wound Healing in Isolation Reared Rats SO PLOS ONE LA English DT Article AB Background: Environmental enrichment (EE) fosters attachment behavior through its effect on brain oxytocin levels in the hippocampus and other brain regions, which in turn modulate the hypothalamic-pituitary axis (HPA). Social isolation and other stressors negatively impact physical healing through their effect on the HPA. Therefore, we reasoned that: 1) provision of a rat EE (nest building with NestletsH) would improve wound healing in rats undergoing stress due to isolation rearing and 2) that oxytocin would have a similar beneficial effect on wound healing. Methodology/Principal Findings: In the first two experiments, we provided isolation reared rats with either EE or oxytocin and compared their wound healing to group reared rats and isolation reared rats that did not receive Nestlets or oxytocin. In the third experiment, we examined the effect of Nestlets on open field locomotion and immediate early gene (IEG) expression. We found that isolation reared rats treated with Nestlets a) healed significantly better than without Nestlets, 2) healed at a similar rate to rats treated with oxytocin, 3) had decreased hyperactivity in the open field test, and 4) had normalized IEG expression in brain hippocampus. Conclusions/Significance: This study shows that when an EE strategy or oxytocin is given to isolation reared rats, the peripheral stress response, as measured by burn injury healing, is decreased. The findings indicate an association between the effect of nest making on wound healing and administration of the pro-bonding hormone oxytocin. Further elucidation of this animal model should lead to improved understanding of how EE strategies can ameliorate poor wound healing and other symptoms that result from isolation stress. RP Vitalo, A (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM gfricchione@partners.org; jblevine@partners.org RI Hoge, Elizabeth/H-5879-2012; Levine, John/G-6221-2015 OI Hoge, Elizabeth/0000-0002-5513-2292; NR 47 TC 19 Z9 20 U1 2 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 13 PY 2009 VL 4 IS 5 AR e5523 DI 10.1371/journal.pone.0005523 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 444WA UT WOS:000266009900015 PM 19436750 ER PT J AU Nilsson, J Skog, J Nordstrand, A Baranov, V Mincheva-Nilsson, L Breakefield, XO Widmark, A AF Nilsson, J. Skog, J. Nordstrand, A. Baranov, V. Mincheva-Nilsson, L. Breakefield, X. O. Widmark, A. TI Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE prostate cancer; prostasomes; tumour exosomes; biomarkers ID PROMOTE TUMOR-GROWTH; DIAGNOSTIC BIOMARKERS; FUSION; GENE; SEDIMENTS; ANTIGEN; TMPRSS2; PCA3 AB Herein, we describe a novel approach in the search for prostate cancer biomarkers, which relies on the transcriptome within tumour exosomes. As a proof-of-concept, we show the presence of two known prostate cancer biomarkers, PCA-3 and TMPRSS2: ERG the in exosomes isolated from urine of patients, showing the potential for diagnosis and monitoring cancer patients status. British Journal of Cancer ( 2009) 100, 1603-1607. doi: 10.1038/sj.bjc.6605058 www.bjcancer.com Published online 28 April 2009 (C) 2009 Cancer Research UK C1 [Nilsson, J.] VU Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp, Dept Neurosurg, Amsterdam, Netherlands. [Nilsson, J.; Nordstrand, A.; Widmark, A.] Umea Univ, Dept Radiat Sci, Umea, Sweden. [Skog, J.; Breakefield, X. O.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Skog, J.; Breakefield, X. O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Skog, J.; Breakefield, X. O.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Baranov, V.; Mincheva-Nilsson, L.] Umea Univ, Dept Clin Immunol, Umea, Sweden. RP Nilsson, J (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Canc Ctr Amsterdam, Room 3-60,Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM j.nilsson@vumc.nl FU Swedish Cancer Research Foundation [070604, 080560]; Wenner-Gren Foundation; Stiftelsen Olle Engkvist Byggmastare; NCI [CA86355, CA69246]; Lions Research Foundation; Umea University, Sweden FX This work was supported by grants from Swedish Cancer Research Foundation (Project Nr. 070604 AW and Nr. 080560 LM-N), Wenner-Gren Foundation (JS), Stiftelsen Olle Engkvist Byggmastare (JS), NCI CA86355 (XOB), NCI CA69246 (XOB) and the Lions Research Foundation, Umea University, Sweden (AW, JN, LM-N). The patients participating in the study are gratefully acknowledged. JS is also a consultant for Exosome Diagnostics Inc. NR 19 TC 224 Z9 240 U1 7 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY 12 PY 2009 VL 100 IS 10 BP 1603 EP 1607 DI 10.1038/sj.bjc.6605058 PG 5 WC Oncology SC Oncology GA 445BR UT WOS:000266025100012 PM 19401683 ER PT J AU Bloch, KD AF Bloch, Kenneth D. TI Careers in Basic Cardiovascular Research SO CIRCULATION LA English DT Article DE research; laboratory research; health occupations ID GUIDE C1 [Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Bloch, KD (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Anesthesia Ctr Crit Care Res, Jackson 4,55 Fruit St, Boston, MA 02114 USA. EM kdbloch@partners.org FU NHLBI [T32 HL007208]; American Heart Association; Department of Anesthesia and Critical Care; Cardiology Division; Cardiovascular Research Center at the Massachusetts General Hospital FX The author acknowledges funding from the NHLBI, which has supported a research training program in cardiovascular science based at the Massachusetts General Hospital for >30 years (T32 HL007208) and funding from the American Heart Association, which has provided generous support for both fellows and faculty in the Department of Anesthesia and Critical Care, the Cardiology Division, and the Cardiovascular Research Center at the Massachusetts General Hospital. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 12 PY 2009 VL 119 IS 18 BP 2526 EP 2530 DI 10.1161/CIRCULATIONAHA.107.752709 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 444WP UT WOS:000266011500014 PM 19433769 ER PT J AU Pfister, EL Kennington, L Straubhaar, J Wagh, S Liu, WZ DiFiglia, M Landwehrmeyer, B Vonsattel, JP Zamore, PD Aronin, N AF Pfister, Edith L. Kennington, Lori Straubhaar, Juerg Wagh, Sujata Liu, Wanzhou DiFiglia, Marian Landwehrmeyer, Bernhard Vonsattel, Jean-Paul Zamore, Phillip D. Aronin, Neil TI Five siRNAs Targeting Three SNPs May Provide Therapy for Three-Quarters of Huntington's Disease Patients SO CURRENT BIOLOGY LA English DT Article ID RNA INTERFERENCE; NUCLEOTIDE MISMATCHES; MUTANT HUNTINGTIN; MODEL MOUSE; IN-VIVO; ALLELE; NEURODEGENERATION; GENE; SOD1; NEUROPATHOLOGY AB Among dominant neurodegenerative disorders, Huntington's disease (HD) is perhaps the best candidate for treatment with small interfering RNAs (siRNAs) [1-9]. Invariably fatal, HD is caused by expansion of a CAG repeat in the Huntingtin gene, creating an extended polyglutamine tract that makes the Huntingtin protein toxic [10]. Silencing mutant Huntingtin messenger RNA (mRNA) should provide therapeutic benefit, but normal Huntingtin likely contributes to neuronal function [11-13]. No si RNA strategy can yet distinguish among the normal and disease Huntingtin alleles and other mRNAs containing CAG repeats [14]. siRNAs targeting the disease isoform of a heterozygous single-nucleotide polymorphism (SNP) in Huntingtin provide an alternative [15-19]. We sequenced 22 predicted SNP sites in 225 human samples corresponding to HD and control subjects. We find that 48% of our patient population is heterozygous at a single SNP site; one isoform of this SNP is associated with HD. Several other SNP sites are frequently heterozygous. Consequently, five allele-specific siRNAs, corresponding to just three SNP sites, could be used to treat three-quarters of the United States and European HD patient populations. We have designed and validated selective siRNAs for the three SNP sites, laying the foundation for allele-specific RNA interference (RNAi) therapy for HD. C1 [Zamore, Phillip D.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Dept Biochem & Mol Biol, Worcester, MA 01605 USA. [Pfister, Edith L.; Kennington, Lori; Straubhaar, Juerg; Wagh, Sujata; Liu, Wanzhou; Aronin, Neil] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Dept Med, Worcester, MA 01605 USA. [DiFiglia, Marian] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Landwehrmeyer, Bernhard] Univ Ulm, D-89069 Ulm, Germany. [Vonsattel, Jean-Paul] Columbia Univ, Sch Med, New York, NY 10032 USA. RP Zamore, PD (reprint author), Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Dept Biochem & Mol Biol, Worcester, MA 01605 USA. EM phillip.zamore@umassmed.edu; neil.aronin@umassmed.edu RI Zamore, Phillip/A-8941-2013; OI Landwehrmeyer, Georg Bernhard/0000-0003-3375-790X FU National Institutes of Health (NIH) [NS38194]; Diabetes and Endocrinology Research Center [P30DK032520-25]; Cure Huntington's Disease Foundation (CHDI); NIH [2T32DK007302-31] FX We thank members of the Zamore and Aronin laboratories for encouragement, helpful discussions and comments on the manuscript. This work was supported, in part, by grants from the National Institutes of Health (NIH) to N.A., M.D., and P.D.Z. (NS38194); from the Diabetes and Endocrinology Research Center (P30DK032520-25); and from the Cure Huntington's Disease Foundation (CHDI) to N.A. and P.D.Z. S.W. was supported by an NIH grant (2T32DK007302-31) to the UMass Endocrine Training Program. P.D.Z. is a cofounder and member of the scientific advisory board of Alnylam Pharmaceuticals, Inc. NR 26 TC 125 Z9 127 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 12 PY 2009 VL 19 IS 9 BP 774 EP 778 DI 10.1016/j.cub.2009.03.030 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 446OU UT WOS:000266131800031 PM 19361997 ER PT J AU Schacter, DL Addis, DR AF Schacter, Daniel L. Addis, Donna Rose TI On the nature of medial temporal lobe contributions to the constructive simulation of future events SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE memory; mental simulation; future thinking; hippocampus; medial temporal lobe; parahippocampal cortex ID MENTAL TIME-TRAVEL; AUTOBIOGRAPHICAL MEMORY; EPISODIC MEMORY; PHENOMENAL CHARACTERISTICS; HIPPOCAMPAL ACTIVATION; RETRIEVAL; IMAGINE; BRAIN; ASSOCIATIONS; RECOGNITION AB A rapidly growing number of studies indicate that imagining or simulating possible future events depends on much of the same neural machinery as does remembering past events. One especially striking finding is that the medial temporal lobe (MTL), which has long been linked to memory function, appears to be similarly engaged during future event simulation. This paper focuses on the role of two MTL regions - the hippocampus and parahippocampal cortex - in thinking about the future and building mental simulations. C1 [Schacter, Daniel L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Schacter, Daniel L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Addis, Donna Rose] Univ Auckland, Dept Psychol, Auckland 1142, New Zealand. RP Schacter, DL (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM dls@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061; Addis, Donna Rose/0000-0002-6231-1491 FU NIMH; NIA FX The preparation of this paper was supported by grants from the NIMH and NIA. We thank Adrian Gilmore for his help with the preparation of the manuscript. NR 55 TC 113 Z9 116 U1 0 U2 11 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD MAY 12 PY 2009 VL 364 IS 1521 BP 1245 EP 1253 DI 10.1098/rstb.2008.0308 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 425UE UT WOS:000264662000008 PM 19528005 ER PT J AU Barrett, LF Bar, M AF Barrett, L. F. Bar, Moshe TI See it with feeling: affective predictions during object perception SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Review DE affect; emotion; perception; prediction; amygdala; orbitofrontal cortex ID MEDIAL PREFRONTAL CORTEX; TOP-DOWN FACILITATION; HUMAN ORBITOFRONTAL CORTEX; TEMPORAL AREAS TE; MACAQUE MONKEYS; RHESUS-MONKEY; VISUAL PATHWAYS; SUBCORTICAL CONNECTIONS; RESPONSE PROPERTIES; ANATOMIC BASIS AB People see with feeling. We 'gaze', 'behold', 'stare', 'gape' and 'glare'. In this paper, we develop the hypothesis that the brain's ability to see in the present incorporates a representation of the affective impact of those visual sensations in the past. This representation makes up part of the brain's prediction of what the visual sensations stand for in the present, including how to act on them in the near future. The affective prediction hypothesis implies that responses signalling an object's salience, relevance or value do not occur as a separate step after the object is identified. Instead, affective responses support vision from the very moment that visual stimulation begins. C1 [Barrett, L. F.] Boston Coll, Chestnut Hill, MA 02467 USA. [Barrett, L. F.; Bar, Moshe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RP Barrett, LF (reprint author), Boston Coll, Chestnut Hill, MA 02467 USA. EM barretli@bc.edu FU NIH [R01NS050615, DP1OD003312]; National Institute of Aging [AG030311]; National Science Foundation [BCS 0721260, BCS 0527440]; Army Research Institute [W91WAW]; Cattell; American Philosophical Society FX Deep thanks to Michael May for sharing his thoughts and experiences. We also thank Eliza Bliss-Moreau, Krysal Yu and Jasmine Boshyan who helped with the preparation of figures. Thanks to Daniel Gilbert and the members of the Barrett and Bar laboratories who made helpful comments on the previous drafts of this manuscript. Preparation of this paper was supported by NIH grant R01NS050615 to M. B., and a National Institutes of Health Director's Pioneer Award (DP1OD003312), grants from the National Institute of Aging (AG030311) and the National Science Foundation (BCS 0721260; BCS 0527440) and a contract with the Army Research Institute (W91WAW), as well as by a Cattell Award and a fellowship from the American Philosophical Society to L. F. B. NR 104 TC 154 Z9 155 U1 5 U2 24 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD MAY 12 PY 2009 VL 364 IS 1521 BP 1325 EP 1334 DI 10.1098/rstb.2008.0312 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 425UE UT WOS:000264662000017 PM 19528014 ER PT J AU Karch, CM Prudencio, M Winkler, DD Hart, PJ Borchelt, DR AF Karch, Celeste M. Prudencio, Mercedes Winkler, Duane D. Hart, P. John Borchelt, David R. TI Role of mutant SOD1 disulfide oxidation and aggregation in the pathogenesis of familial ALS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neurodegenerative disease; protein misfolding ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOLECULAR-WEIGHT COMPLEXES; SUPEROXIDE-DISMUTASE 1; MOUSE MODEL; TRANSGENIC MICE; SPINAL-CORDS; DISEASE; COPPER; SUPEROXIDE-DISMUTASE-1; MUTATIONS AB Transgenic mice that model familial (f) ALS, caused by mutations in superoxide dismutase (SOD) 1, develop paralysis with pathology that includes the accumulation of aggregated forms of the mutant protein. Using a highly sensitive detergent extraction assay, we traced the appearance and abundance of detergent-insoluble and disulfide cross-linked aggregates of SOD1 throughout the disease course of SOD1-fALS mice (G93A, G37R, and H46R/H48Q). We demonstrate that the accumulation of disulfide cross-linked, detergent-insoluble, aggregates of mutant SOD1 occurs primarily in the later stages of the disease, concurrent with the appearance of rapidly progressing symptoms. We find no evidence for a model in which aberrant intermolecular disulfide bonding has an important role in promoting the aggregation of mutant SOD1, instead, such cross-linking appears to be a secondary event. Also, using both cell culture and mouse models, we find that mutant protein lacking the normal intramolecular disulfide bond is a major component of the insoluble SOD1 aggregates. Overall, our findings suggest a model in which soluble forms of mutant SOD1 initiate disease with larger aggregates implicated only in rapidly progressing events in the final stages of disease. Within the final stages of disease, abnormalities in the oxidation of a normal intramolecular disulfide bond in mutant SOD1 facilitate the aggregation of mutant protein. C1 [Karch, Celeste M.; Prudencio, Mercedes; Borchelt, David R.] Univ Florida, McKnight Brain Inst, Dept Neurosci, Gainesville, FL 32610 USA. [Winkler, Duane D.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Winkler, Duane D.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. [Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Borchelt, DR (reprint author), Univ Florida, McKnight Brain Inst, Dept Neurosci, Gainesville, FL 32610 USA. EM borchelt@mbi.ufl.edu OI Karch, Celeste/0000-0002-6854-5547; Prudencio, Mercedes/0000-0002-4894-4858 FU National Institutes of Health [P01 NS049134] FX We thank Hilda Brown (University of Florida) for advice and assistance in generating the SOD1 expression constructs, Susan Fromholt (University of Florida) for assistance in genotyping the mice, and our colleagues for thoughtful discussions. This work was supported by National Institutes of Health Grant P01 NS049134 (to P. J. H. and D. R. B.). NR 33 TC 93 Z9 94 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 12 PY 2009 VL 106 IS 19 BP 7774 EP 7779 DI 10.1073/pnas.0902505106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 447RG UT WOS:000266208900020 PM 19416874 ER PT J AU Kroh, HK Panizzi, P Bock, PE AF Kroh, Heather K. Panizzi, Peter Bock, Paul E. TI Von Willebrand factor-binding protein is a hysteretic conformational activator of prothrombin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE coagulation; proteinases; Staphylococcus aureus; zymogens; hysteresis ID STAPHYLOCOCCUS-AUREUS; BOVINE TRYPSINOGEN; STAPHYLOCOAGULASE; RECOGNITION; ZYMOGEN; STAPHYLOTHROMBIN; STREPTOKINASE; TRANSITION; COMPLEXES; MECHANISM AB Von Willebrand factor-binding protein (VWbp), secreted by Staphylococcus aureus, displays secondary structural homology to the 3-helix bundle, D1 and D2 domains of staphylocoagulase (SC), a potent conformational activator of the blood coagulation zymogen, prothrombin (ProT). In contrast to the classical proteolytic activation mechanism of trypsinogen-like serine proteinase zymogens, insertion of the first 2 residues of SC into the NH(2)-terminal binding cleft on ProT (molecular sexuality) induces rapid conformational activation of the catalytic site. Based on plasma-clotting assays, the target zymogen for VWbp may be ProT, but this has not been verified, and the mechanism of ProT activation is unknown. We demonstrate that VWbp activates ProT conformationally in a mechanism requiring its Val(1)-Val(2) residues. By contrast to SC, full time-course kinetic studies of ProT activation by VWbp demonstrate that it activates ProT by a substrate-dependent, hysteretic kinetic mechanism. VWbp binds weakly to ProT (K(D) 2.5 mu M) to form an inactive complex, which is activated through a slow conformational change by tripeptide chromogenic substrates and its specific physiological substrate, identified here as fibrinogen (Fbg). This mechanism increases the specificity of ProT activation by delaying it in a slow reversible process, with full activation requiring binding of Fbg through an exosite expressed on the activated ProT*.VWbp complex. The results suggest that this unique mechanism regulates pathological fibrin (Fbn) deposition to VWF-rich areas during S. aureus endocarditis. C1 [Kroh, Heather K.; Bock, Paul E.] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. [Panizzi, Peter] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Bock, PE (reprint author), Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. EM paul.bock@vanderbilt.edu OI Panizzi, Peter/0000-0003-0141-8807 FU National Institutes of Health [R37 HL071544]; National Heart, Lung, and Blood Institute; National Institutes of Health Training Grant [2-T32 HL07751] FX This work was supported by National Institutes of Health Grant R37 HL071544 from the National Heart, Lung, and Blood Institute (to P. E. B.). H. K. K. was supported by National Institutes of Health Training Grant 2-T32 HL07751. NR 34 TC 37 Z9 37 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 12 PY 2009 VL 106 IS 19 BP 7786 EP 7791 DI 10.1073/pnas.0811750106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 447RG UT WOS:000266208900022 PM 19416890 ER PT J AU Chakraborty, T Perlot, T Subrahmanyam, R Jani, A Goff, PH Zhang, Y Ivanova, I Alt, FW Sen, R AF Chakraborty, Tirtha Perlot, Thomas Subrahmanyam, Ramesh Jani, Anant Goff, Peter H. Zhang, Yu Ivanova, Irina Alt, Frederick W. Sen, Ranjan TI A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID BETA-GLOBIN LOCUS; RECEPTOR-GENE REARRANGEMENT; MOUSE IGH LOCUS; HISTONE ACETYLATION; CONTROL REGION; V(D)J RECOMBINATION; CORE REGION; CHROMATIN; METHYLATION; MU AB A tissue-specific transcriptional enhancer, E mu, has been implicated in developmentally regulated recombination and transcription of the immunoglobulin heavy chain (IgH) gene locus. We demonstrate that deleting 220 nucleotides that constitute the core E. results in partially active locus, characterized by reduced histone acetylation, chromatin remodeling, transcription, and recombination, whereas other hallmarks of tissue-specific locus activation, such as loss of H3K9 dimethylation or gain of H3K4 dimethylation, are less affected. These observations define E mu-independent and E mu-dependent phases of locus activation that reveal an unappreciated epigenetic hierarchy in tissue-specific gene expression. C1 [Chakraborty, Tirtha; Subrahmanyam, Ramesh; Ivanova, Irina; Sen, Ranjan] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. [Jani, Anant] Yale Univ, Sch Med, Program Immunol, New Haven, CT 06510 USA. [Perlot, Thomas] Univ Vienna, A-1010 Vienna, Austria. [Perlot, Thomas; Goff, Peter H.; Zhang, Yu; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Perlot, Thomas; Goff, Peter H.; Zhang, Yu; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA. RP Sen, R (reprint author), NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. EM rs465z@nih.gov RI Subrahmanyam, Ramesh/K-5503-2012 FU National Institutes of Health [AI2047]; Intramural Research Program of the National Institute on Aging (Baltimore, MD) FX T. Perlot is supported by a Boehringer Ingelheim Fonds PhD scholarship. F. W. Alt is an investigator of the Howard Hughes Medical Institute. This work was supported by National Institutes of Health grant AI2047 (to F. W. Alt) and by the Intramural Research Program of the National Institute on Aging (Baltimore, MD). The authors have no conflicting financial interests. NR 35 TC 30 Z9 31 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 11 PY 2009 VL 206 IS 5 BP 1019 EP 1027 DI 10.1084/jem.20081621 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 444WB UT WOS:000266010000009 PM 19414554 ER PT J AU Diller, L Chow, EJ Gurney, JG Hudson, MM Kadin-Lottick, NS Kawashima, TI Leisenring, WM Meacham, LR Mertens, AC Mulrooney, DA Oeffinger, KC Packer, RJ Robison, LL Sklar, CA AF Diller, Lisa Chow, Eric J. Gurney, James G. Hudson, Melissa M. Kadin-Lottick, Nina S. Kawashima, Toana I. Leisenring, Wendy M. Meacham, Lillian R. Mertens, Ann C. Mulrooney, Daniel A. Oeffinger, Kevin C. Packer, Roger J. Robison, Leslie L. Sklar, Charles A. TI Chronic Disease in the Childhood Cancer Survivor Study Cohort: A Review of Published Findings SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GROWTH-HORMONE TREATMENT; BODY-MASS-INDEX; LEPTIN RECEPTOR GENE; LONG-TERM SURVIVORS; FUNCTIONAL STATUS INDEX; CENTRAL-NERVOUS-SYSTEM; GH-DEFICIENT CHILDREN; HODGKINS-DISEASE; ADULT SURVIVORS C1 [Diller, Lisa] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Dept Canc Prevent, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Dept Clin Stat, Seattle, WA 98104 USA. Univ Michigan, Ctr Comprehens Canc, Dept Pediat, Ann Arbor, MI 48109 USA. St Jude Childrens Res Hosp, Dept Oncol Epidemiol & Canc Control, Memphis, TN 38105 USA. Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Childrens Natl Med Ctr, Neurosci Res Ctr, Washington, DC 20010 USA. RP Diller, L (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Mailstop SW312, Boston, MA 02115 USA. EM lisa_diller@dfci.harvard.edu FU NCI NIH HHS [U24 CA055727, U24-CA55727] NR 110 TC 137 Z9 139 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2009 VL 27 IS 14 BP 2339 EP 2355 DI 10.1200/JCO.2008.21.1953 PG 17 WC Oncology SC Oncology GA 447MM UT WOS:000266195200005 PM 19364955 ER PT J AU Nathan, PC Ford, JS Henderson, TO Hudson, MM Emmons, KM Casillas, JN Lown, EA Ness, KK Oeffinger, KC AF Nathan, Paul C. Ford, Jennifer S. Henderson, Tara O. Hudson, Melissa M. Emmons, Karen M. Casillas, Jacqueline N. Lown, E. Anne Ness, Kirsten K. Oeffinger, Kevin C. TI Health Behaviors, Medical Care, and Interventions to Promote Healthy Living in the Childhood Cancer Survivor Study Cohort SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LONG-TERM SURVIVORS; GROWTH-HORMONE DEFICIENCY; HEPATITIS-C INFECTION; ADULT SURVIVORS; HODGKINS-DISEASE; BREAST-CANCER; FOLLOW-UP; PHYSICAL-ACTIVITY; DENTAL ABNORMALITIES AB Childhood cancer survivors are at risk for medical and psychosocial late effects as a result of their cancer and its therapy. Promotion of healthy lifestyle behaviors and provision of regular risk-based medical care and surveillance may modify the evolution of these late effects. This manuscript summarizes publications from the Childhood Cancer Survivor Study (CCSS) that have examined health behaviors, risk-based health care, and interventions to promote healthy lifestyle practices. Long-term survivors use tobacco and alcohol and have inactive lifestyles at higher rates than is ideal given their increased risk of cardiac, pulmonary, and metabolic late effects. Nearly 90% of survivors report receiving some form of medical care. However, only 18% report medical visits related to their prior cancer that include discussion or ordering of screening tests or counseling on how to reduce the specific risks arising from their cancer. One low-cost, peer-driven intervention trial has been successful in improving smoking cessation within the CCSS cohort. On the basis of data from CCSS investigations, several trials to promote improved medical surveillance among high-risk groups within the cohort are underway. Despite their long-term risks, many survivors of childhood cancer engage in risky health behaviors and do not receive adequate risk-based medical care. C1 [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Chicago Pritzker, Sch Med, Chicago, IL USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Alcohol Res Grp, Emeryville, CA USA. RP Oeffinger, KC (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA. EM oeffingk@mskcc.org FU NCI NIH HHS [U24 CA055727, U24 CA55727] NR 83 TC 101 Z9 101 U1 7 U2 13 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2009 VL 27 IS 14 BP 2363 EP 2373 DI 10.1200/JCO.2008.21.1441 PG 11 WC Oncology SC Oncology GA 447MM UT WOS:000266195200007 PM 19255308 ER PT J AU Zeltzer, LK Recklitis, C Buchbinder, D Zebrack, B Casillas, J Tsao, JCI Lu, Q Krull, K AF Zeltzer, Lonnie K. Recklitis, Christopher Buchbinder, David Zebrack, Bradley Casillas, Jacqueline Tsao, Jennie C. I. Lu, Qian Krull, Kevin TI Psychological Status in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID QUALITY-OF-LIFE; LONG-TERM SURVIVORS; RANDOMIZED CLINICAL-TRIAL; BREAST-CANCER; ADULT SURVIVORS; NEUROCOGNITIVE SEQUELAE; HODGKINS-DISEASE; SELF-MANAGEMENT; HEALTH; OUTCOMES AB Psychological quality of life (QOL), health-related QOL (HRQOL), and life satisfaction outcomes and their associated risk factors are reviewed for the large cohort of survivors and siblings in the Childhood Cancer Survivor Study (CCSS). This review includes previously published manuscripts that used CCSS data focused on psychological outcome measures, including the Brief Symptom Inventory (BSI-18), the Medical Outcomes Survey Short Form-36 (SF-36), the Cantril Ladder of Life, and other self-report questionnaires. Comparisons and contrasts are made between siblings and survivors, and to normative data when available, in light of demographic/health information and abstracted data from the medical record. These studies demonstrate that a significant proportion of survivors report more symptoms of global distress and poorer physical, but not emotional, domains of HRQOL. Other than brain tumor survivors, most survivors report both good present and expected future life satisfaction. Risk factors for psychological distress and poor HRQOL are female sex, lower educational attainment, unmarried status, annual household income less than $20,000, unemployment, lack of health insurance, presence of a major medical condition, and treatment with cranial radiation and/or surgery. Cranial irradiation impacted neurocognitive outcomes, especially in brain tumor survivors. Psychological distress also predicted poor health behaviors, including smoking, alcohol use, fatigue, and altered sleep. Psychological distress and pain predicted use of complementary and alternative medicine. Overall, most survivors are psychologically healthy and report satisfaction with their lives. However, certain groups of childhood cancer survivors are at high risk for psychological distress, neurocognitive dysfunction, and poor HRQOL, especially in physical domains. These findings suggest targeting interventions for groups at highest risk for adverse outcomes and examining the positive growth that remains despite the trauma of childhood cancer. C1 [Zeltzer, Lonnie K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA. Univ Houston, Dept Psychol, Houston, TX USA. St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. RP Zeltzer, LK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, 22-464 MDCC,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM lzeltzer@mednet.ucla.edu FU NCI NIH HHS [U24 CA055727, U24-CA55727] NR 62 TC 204 Z9 205 U1 8 U2 36 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2009 VL 27 IS 14 BP 2396 EP 2404 DI 10.1200/JCO.2008.21.1433 PG 9 WC Oncology SC Oncology GA 447MM UT WOS:000266195200011 PM 19255309 ER PT J AU Morris, ZS McClatchey, AI AF Morris, Zachary S. McClatchey, Andrea I. TI The Neurofibroma Cell of Origin: SKPs Expand the Playing Field SO CELL STEM CELL LA English DT Editorial Material ID NF1; TYPE-1 AB Mounting evidence suggests that stem/progenitor cells maybe the cells of origin for many tumor types. In this issue of Cell Stem Cell, Le et al. (2009) demonstrate that skin-derived precursors (SKPs) can initiate dermal neurofibromas and highlight the importance of the microenvironment in the formation of this complex tumor. C1 [Morris, Zachary S.; McClatchey, Andrea I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc Res, Charlestown, MA 02129 USA. [Morris, Zachary S.; McClatchey, Andrea I.] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. RP McClatchey, AI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc Res, 149 13th St, Charlestown, MA 02129 USA. EM mcclatch@helix.mgh.harvard.edu OI Morris, Zachary/0000-0001-5558-3547 NR 10 TC 2 Z9 2 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAY 8 PY 2009 VL 4 IS 5 BP 371 EP 372 DI 10.1016/j.stem.2009.04.010 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 445SF UT WOS:000266071100001 PM 19427284 ER PT J AU Pakotiprapha, D Liu, Y Verdine, GL Jeruzalmi, D AF Pakotiprapha, Danaya Liu, Yi Verdine, Gregory L. Jeruzalmi, David TI A Structural Model for the Damage-sensing Complex in Bacterial Nucleotide Excision Repair SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; (A)BC EXCINUCLEASE; LIGHT-SCATTERING; COUPLING FACTOR; ACTIVE-SITE; NMR SYSTEM; 5 INCISION; UVRB; DNA; BINDING AB Nucleotide excision repair is distinguished from other DNA repair pathways by its ability to process a wide range of structurally unrelated DNA lesions. In bacteria, damage recognition is achieved by the UvrA.UvrB ensemble. Here, we report the structure of the complex between the interaction domains of UvrA and UvrB. These domains are necessary and sufficient for full-length UvrA and UvrB to associate and thereby form the DNA damage-sensing complex of bacterial nucleotide excision repair. The crystal structure and accompanying biochemical analyses suggest a model for the complete damage-sensing complex. C1 [Pakotiprapha, Danaya; Liu, Yi; Verdine, Gregory L.; Jeruzalmi, David] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Pakotiprapha, Danaya; Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. RP Verdine, GL (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM gregory_verdine@harvard.edu; dj@mcb.harvard.edu RI Pakotiprapha, Danaya/B-1032-2013 OI Pakotiprapha, Danaya/0000-0002-1639-6105 FU National Institutes of Health [CA100742]; National Center for Research Resources [RR-15301]; National Institutes of Health FX This work was supported, in whole or in part, by National Institutes of Health Grant CA100742 (to G. L. V.). This work was also supported by Award RR-15301 from the National Center for Research Resources at the National Institutes of Health. NR 34 TC 28 Z9 28 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 8 PY 2009 VL 284 IS 19 BP 12837 EP 12844 DI 10.1074/jbc.M900571200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 440GH UT WOS:000265688300029 PM 19287003 ER PT J AU Kimbrel, EA Kung, AL AF Kimbrel, Erin A. Kung, Andrew L. TI The F-box Protein beta-TrCp1/Fbw1a Interacts with p300 to Enhance beta-Catenin Transcriptional Activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UBIQUITIN LIGASE RECEPTOR; COLORECTAL-CANCER CELLS; CREB-BINDING PROTEIN; GENE-EXPRESSION; DEPENDENT DEGRADATION; MOLECULAR-MECHANISMS; COACTIVATOR P300; COLON-CARCINOMA; MESSENGER-RNA; ACTIVATION AB Hyperactivated beta-catenin is a commonly found molecular abnormality in colon cancer, and its nuclear accumulation is thought to promote the expression of genes associated with cellular proliferation and transformation. The p300 transcriptional co-activator binds to beta-catenin and facilitates transcription by recruiting chromatin remodeling complexes and general transcriptional apparatus. We have found that beta-TrCp1/Fbw1a, a member of the Skp1/Cullin/Rbx1/F-box E3 ubiquitin ligase complex, binds directly to p300 and co-localizes with it to beta-catenin target gene promoters. Our data show that Fbw1a, which normally targets beta-catenin for degradation, works together with p300 to enhance the transcriptional activity of beta-catenin, whereas other F-box/WD40 proteins do not. Fbw1a also cooperates with p300 to co-activate transcription by SMAD3, another Fbw1a ubiquitylation target, but not p53 or HIF-1 alpha, which are substrates for other ubiquitin ligase complexes. These results suggest that, although Fbw1a is part of a negative feedback loop for controlling beta-catenin levels in normal cells, its overexpression and binding to p300 may contribute to hyperactivated beta-catenin transcriptional activity in colon cancer cells. C1 [Kung, Andrew L.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kung, AL (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM andrew_kung@dfci.harvard.edu FU Dana-Farber Cancer Institute Pediatric Oncology Department FX This work was supported by an Abraham fellowship through the Dana-Farber Cancer Institute Pediatric Oncology Department and an Aid for Cancer Research fellowship (to E. A. K.). NR 71 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 8 PY 2009 VL 284 IS 19 BP 13033 EP 13044 DI 10.1074/jbc.M901248200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 440GH UT WOS:000265688300051 PM 19297328 ER PT J AU Guan, JS Haggarty, SJ Giacometti, E Dannenberg, JH Joseph, N Gao, J Nieland, TJF Zhou, Y Wang, XY Mazitschek, R Bradner, JE DePinho, RA Jaenisch, R Tsai, LH AF Guan, Ji-Song Haggarty, Stephen J. Giacometti, Emanuela Dannenberg, Jan-Hermen Joseph, Nadine Gao, Jun Nieland, Thomas J. F. Zhou, Ying Wang, Xinyu Mazitschek, Ralph Bradner, James E. DePinho, Ronald A. Jaenisch, Rudolf Tsai, Li-Huei TI HDAC2 negatively regulates memory formation and synaptic plasticity SO NATURE LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; GENE-EXPRESSION; MOUSE MODEL; HUNTINGTONS-DISEASE; CHROMATIN; ACETYLATION; MICE; MODULATION; RECEPTORS; MECHANISM AB Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACis requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not that of HDAC1, decreased dendritic spine density, synapse number, synaptic plasticity and memory formation. Conversely, Hdac2 deficiency resulted in increased synapse number and memory facilitation, similar to chronic treatment with HDACis in mice. Notably, reduced synapse number and learning impairment of HDAC2-overexpressing mice were ameliorated by chronic treatment with HDACis. Correspondingly, treatment with HDACis failed to further facilitate memory formation in Hdac2-deficient mice. Furthermore, analysis of promoter occupancy revealed an association of HDAC2 with the promoters of genes implicated in synaptic plasticity and memory formation. Taken together, our results suggest that HDAC2 functions in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory. These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment. C1 [Guan, Ji-Song; Joseph, Nadine; Gao, Jun; Zhou, Ying; Wang, Xinyu; Tsai, Li-Huei] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Guan, Ji-Song; Joseph, Nadine; Gao, Jun; Zhou, Ying; Wang, Xinyu; Tsai, Li-Huei] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Guan, Ji-Song; Haggarty, Stephen J.; Joseph, Nadine; Nieland, Thomas J. F.; Mazitschek, Ralph; Bradner, James E.; Tsai, Li-Huei] Harvard Univ, Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Guan, Ji-Song; Haggarty, Stephen J.; Joseph, Nadine; Nieland, Thomas J. F.; Mazitschek, Ralph; Bradner, James E.; Tsai, Li-Huei] MIT, Cambridge, MA 02142 USA. [Haggarty, Stephen J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Cambridge, MA 02142 USA. [Giacometti, Emanuela; Jaenisch, Rudolf] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Giacometti, Emanuela; Jaenisch, Rudolf] MIT, Dept Biol, Cambridge, MA 02139 USA. [Dannenberg, Jan-Hermen; DePinho, Ronald A.] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA. [Dannenberg, Jan-Hermen; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Dannenberg, Jan-Hermen; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mazitschek, Ralph] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Tsai, LH (reprint author), MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, E25-618, Cambridge, MA 02139 USA. EM lhtsai@mit.edu RI Mazitschek, Ralph/E-3741-2013; OI Mazitschek, Ralph/0000-0002-1105-689X; Guan, Ji-Song /0000-0001-5219-0289; Haggarty, Stephen J./0000-0002-7872-168X FU National Institute of Neurological Disorders and Stroke [2 ROI NS051874]; Stanley Center for Psychiatric Research; National Alliance for Research on Schizophrenia and Depression Foundation; Damon-Runyon Cancer Research Foundation; Dutch Cancer Society; NIH [5-RO1-CA087869, 5-R37-CA084198, 5-RO1-HD0445022]; Robert A. and Renee E. Belfer Institute for Applied Cancer Science FX We thank E. Scolnick, D. Fass, P. Sklar, T. Petryshen, B. A. Samuels, A. Fischer, C. Frank, D. Kim, S. Su and Y. Hayashi for advice and critical reading of the manuscript; T. Petryshen, A. Graybiel, J. Crittenden and M. C. Lewis for providing the T-maze behaviour model; R. Neve for providing tdTomato HSV. Funding was provided by a grant from the National Institute of Neurological Disorders and Stroke (2 ROI NS051874) to L.-H. T., by a research fund from the Stanley Center for Psychiatric Research to L.-H. T. and S. J. H., by the National Alliance for Research on Schizophrenia and Depression Foundation to S. J. H.; by a fellowship from the Damon-Runyon Cancer Research Foundation and The Dutch Cancer Society (KWF) to J. H. D. R. J. is supported by NIH grants (5-RO1-CA087869, 5-R37-CA084198, 5-RO1-HD0445022); R. A. D. is supported by the Robert A. and Renee E. Belfer Institute for Applied Cancer Science. L.-H. T. is an investigator of the Howard Hughes Medical Institute. NR 35 TC 688 Z9 714 U1 5 U2 72 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 7 PY 2009 VL 459 IS 7243 BP 55 EP U58 DI 10.1038/nature07925 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441WN UT WOS:000265801300027 PM 19424149 ER PT J AU Adams, GB Alley, IR Chung, U Chabner, KT Jeanson, NT Lo Celso, C Marsters, ES Chen, M Weinstein, LS Lin, CP Kronenberg, HM Scadden, DT AF Adams, Gregor B. Alley, Ian R. Chung, Ung-il Chabner, Karissa T. Jeanson, Nathaniel T. Lo Celso, Cristina Marsters, Emily S. Chen, Min Weinstein, Lee S. Lin, Charles P. Kronenberg, Henry M. Scadden, David T. TI Haematopoietic stem cells depend on G alpha(s)-mediated signalling to engraft bone marrow SO NATURE LA English DT Article ID IN-VIVO; CHOLERA-TOXIN; MICE; DIFFERENTIATION; LYMPHOPOIESIS; MYELOPOIESIS; MIGRATION; SELECTINS; CXCR4 AB Haematopoietic stem and progenitor cells (HSPCs) change location during development(1) and circulate in mammals throughout life(2), moving into and out of the bloodstream to engage bone marrow niches in sequential steps of homing, engraftment and retention(3-5). Here we show that HSPC engraftment of bone marrow in fetal development is dependent on the guanine-nucleotide-binding protein stimulatory a subunit (G alpha(s)). HSPCs from adult mice deficient in G alpha(s) (G alpha(-/-)(s)) differentiate and undergo chemotaxis, but also do not home to or engraft in the bone marrow in adult mice and demonstrate a marked inability to engage the marrow microvasculature. If deleted after engraftment, G alpha(s) deficiency did not lead to lack of retention in the marrow, rather cytokine-induced mobilization into the blood was impaired. Testing whether activation of G alpha(s) affects HSPCs, pharmacological activators enhanced homing and engraftment in vivo. G alpha(s) governs specific aspects of HSPC localization under physiological conditions in vivo and may be pharmacologically targeted to improve transplantation efficiency. C1 [Adams, Gregor B.; Alley, Ian R.; Chabner, Karissa T.; Jeanson, Nathaniel T.; Lo Celso, Cristina; Marsters, Emily S.; Scadden, David T.] Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. [Chung, Ung-il; Kronenberg, Henry M.] Harvard Univ, Sch Med, Endocrine Unit, Boston, MA 02114 USA. [Lin, Charles P.] Harvard Univ, Sch Med, Adv Microscopy Program, Ctr Syst Biol, Boston, MA 02114 USA. [Lin, Charles P.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Adams, Gregor B.; Lo Celso, Cristina; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Scadden, David T.] Harvard Univ, Sch Med, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA. [Chen, Min; Weinstein, Lee S.] NIDDKD, Bethesda, MD 20892 USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. EM dscadden@mgh.harvard.edu FU Burroughs Wellcome Fund, Doris Duke Charitable Trust; Harvard Stem Cell Institute; National Institutes of Health FX Financial support for this work was provided by the Burroughs Wellcome Fund, Doris Duke Charitable Trust (D. T. S.), the Harvard Stem Cell Institute (C. P. L.) and the National Institutes of Health (G. B. A., C. P. L., H. M. K., D. T. S.). NR 21 TC 41 Z9 42 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 7 PY 2009 VL 459 IS 7243 BP 103 EP U111 DI 10.1038/nature07859 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441WN UT WOS:000265801300038 PM 19322176 ER PT J AU Naik, AD Petersen, LA AF Naik, Aanand D. Petersen, Laura A. TI The Neglected Purpose of Comparative-Effectiveness Research. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Naik, Aanand D.; Petersen, Laura A.] Michael E DeBakey Vet Affairs Med Ctr, Houston Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. [Petersen, Laura A.] Baylor Coll Med, John M Eisenberg Ctr Clin Decis & Commun Sci, Houston, TX 77030 USA. [Naik, Aanand D.; Petersen, Laura A.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Naik, AD (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. FU NIA NIH HHS [K23 AG027144-04, K23 AG027144] NR 5 TC 53 Z9 54 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 7 PY 2009 VL 360 IS 19 BP 1929 EP 1931 DI 10.1056/NEJMp0902195 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 441QN UT WOS:000265784400003 PM 19420362 ER PT J AU Picard, C McCarl, CA Papolos, A Khalil, S Luthy, K Hivroz, C LeDeist, F Rieux-Laucat, F Rechavi, G Rao, A Fischer, A Feske, S AF Picard, Capucine McCarl, Christie-Ann Papolos, Alexander Khalil, Sara Luethy, Kevin Hivroz, Claire LeDeist, Francoise Rieux-Laucat, Frederic Rechavi, Gideon Rao, Anjana Fischer, Alain Feske, Stefan TI Brief Report: STIM1 Mutation Associated with a Syndrome of Immunodeficiency and Autoimmunity. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OPERATED CALCIUM-ENTRY; CRAC CHANNEL; T-CELL; STORE DEPLETION; SENSOR STIM1; CA2+ INFLUX; ACTIVATION; LYMPHOCYTES; ORAI1; OLIGOMERIZATION AB A mutation in ORAI1, the gene encoding the pore-forming subunit of the Ca(sup 2+)-release-activated Ca(sup 2+) (CRAC) channel, abrogates the store-operated entry of Ca(sup 2+) into cells and impairs lymphocyte activation. Stromal interaction molecule 1 (STIM1) in the endoplasmic reticulum activates ORAI1-CRAC channels. We report on three siblings from one kindred with a clinical syndrome of immunodeficiency, hepatosplenomegaly, autoimmune hemolytic anemia, thrombocytopenia, muscular hypotonia, and defective enamel dentition. Two of these patients have a homozygous nonsense mutation in STIM1 that abrogates expression of STIM1 and Ca(sup 2+) influx. C1 [Picard, Capucine; LeDeist, Francoise; Fischer, Alain] Hop Necker Enfants Malad, AP HP, Paris, France. [Picard, Capucine] Necker Fac, INSERM, Unite 550, Lab Genet Humaine Malad Infect, Paris, France. [Picard, Capucine; Rieux-Laucat, Frederic; Fischer, Alain] Paris Descartes Univ, Paris, France. [Hivroz, Claire; LeDeist, Francoise; Rieux-Laucat, Frederic; Fischer, Alain] INSERM, Unite 768, Paris, France. [Hivroz, Claire] Inst Curie, INSERM, Unite 653, Paris, France. [McCarl, Christie-Ann; Papolos, Alexander; Khalil, Sara; Luethy, Kevin; Feske, Stefan] NYU, Sch Med, New York, NY 10016 USA. [LeDeist, Francoise] Ctr Hosp Univ St Justine, Montreal, PQ, Canada. [LeDeist, Francoise] Univ Montreal, Montreal, PQ, Canada. [Rechavi, Gideon] Tel Aviv Univ, Chaim Sheba Med Ctr, IL-69978 Tel Aviv, Israel. [Rechavi, Gideon] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Rao, Anjana] Immune Dis Inst, Boston, MA USA. [Rao, Anjana] Harvard Univ, Sch Med, Boston, MA USA. RP Feske, S (reprint author), NYU, Dept Pathol, Langone Med Ctr, 550 1st Ave, New York, NY 10016 USA. EM feskes01@nyumc.org RI Hivroz, Claire/H-2711-2014; Rieux-Laucat, Frederic/A-7916-2017 OI Rieux-Laucat, Frederic/0000-0001-7858-7866 FU NIAID NIH HHS [R01 AI048213, R01 AI048213-09] NR 31 TC 220 Z9 222 U1 4 U2 15 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 7 PY 2009 VL 360 IS 19 BP 1971 EP 1980 DI 10.1056/NEJMoa0900082 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 441QN UT WOS:000265784400007 PM 19420366 ER PT J AU Fazel, R Dhaliwal, G Saint, S Nallamothu, BK AF Fazel, Reza Dhaliwal, Gurpreet Saint, Sanjay Nallamothu, Brahmajee K. TI A Red Flag. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; EOSINOPHILIA C1 [Fazel, Reza] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30306 USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. [Saint, Sanjay; Nallamothu, Brahmajee K.] Univ Michigan, Sch Med, Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI USA. [Saint, Sanjay; Nallamothu, Brahmajee K.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. RP Fazel, R (reprint author), Emory Univ, Sch Med, Div Cardiol, Bldg A,Suite 1-N,1256 Briarcliff Rd NE, Atlanta, GA 30306 USA. EM rfazel@emory.edu NR 11 TC 6 Z9 6 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 7 PY 2009 VL 360 IS 19 BP 2005 EP 2010 DI 10.1056/NEJMcps0802754 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 441QN UT WOS:000265784400012 PM 19420370 ER PT J AU Razansky, D Vinegoni, C Ntziachristos, V AF Razansky, Daniel Vinegoni, Claudio Ntziachristos, Vasilis TI Imaging of mesoscopic-scale organisms using selective-plane optoacoustic tomography SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID FLUORESCENCE MICROSCOPY; DROSOPHILA-MELANOGASTER; EXPRESSION; SYSTEM; BRAIN AB Mesoscopic-scale living organisms (i.e. 1 mm to 1 cm sized) remain largely inaccessible by current optical imaging methods due to intensive light scattering in tissues. Therefore, imaging of many important model organisms, such as insects, fishes, worms and similarly sized biological specimens, is currently limited to embryonic or other transparent stages of development. This makes it difficult to relate embryonic cellular and molecular mechanisms to consequences in organ function and animal behavior in more advanced stages and adults. Herein, we have developed a selective-plane illumination optoacoustic tomography technique for in vivo imaging of optically diffusive organisms and tissues. The method is capable of whole-body imaging at depths from the sub-millimeter up to centimeter range with a scalable spatial resolution in the order of magnitude of a few tenths of microns. In contrast to pure optical methods, the spatial resolution here is not determined nor limited by light diffusion; therefore, such performance cannot be achieved by any other optical imaging technology developed so far. The utility of the method is demonstrated on several whole-body models and small-animal extremities. C1 [Razansky, Daniel; Ntziachristos, Vasilis] Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, D-85764 Neuherberg, Germany. [Razansky, Daniel; Ntziachristos, Vasilis] Tech Univ Munich, Fac Med, D-81675 Munich, Germany. [Razansky, Daniel; Ntziachristos, Vasilis] Tech Univ Munich, Fac Elect Engn & Informat Technol, D-81675 Munich, Germany. [Razansky, Daniel; Vinegoni, Claudio; Ntziachristos, Vasilis] Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, Charlestown, MA 02115 USA. [Razansky, Daniel; Vinegoni, Claudio; Ntziachristos, Vasilis] Harvard Univ, Sch Med, Charlestown, MA 02115 USA. [Vinegoni, Claudio] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Vinegoni, Claudio] Harvard Univ, Sch Med, Richard B Simches Res Ctr, Boston, MA 02114 USA. RP Razansky, D (reprint author), Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. EM dr@tum.de OI Razansky, Daniel/0000-0001-8676-0964 NR 25 TC 32 Z9 32 U1 0 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 7 PY 2009 VL 54 IS 9 BP 2769 EP 2777 DI 10.1088/0031-9155/54/9/012 PG 9 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 435NJ UT WOS:000265350300012 PM 19369709 ER PT J AU Vrancic, C Trofimov, A Chan, TCY Sharp, GC Bortfeld, T AF Vrancic, Christian Trofimov, Alexei Chan, Timothy C. Y. Sharp, Gregory C. Bortfeld, Thomas TI Experimental evaluation of a robust optimization method for IMRT of moving targets SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MODULATED RADIATION-THERAPY; INTRA-FRACTION-MOTION; LUNG-TUMOR MOTION; CANCER PATIENTS; TRACKING; RADIOTHERAPY; UNCERTAINTY; INTRAFRACTION; STRATEGIES; DELIVERY AB Internal organ motion during radiation therapy, if not considered appropriately in the planning process, has been shown to reduce target coverage and increase the dose to healthy tissues. Standard planning approaches, which use safety margins to handle intrafractional movement of the tumor, are typically designed based on the maximum amplitude of motion, and are often overly conservative. Comparable coverage and reduced dose to healthy organs appear achievable with robust motion-adaptive treatment planning, which considers the expected probability distribution of the average target position and the uncertainty of its realization during treatment delivery. A dosimetric test of a robust optimization method for IMRT was performed, using patient breathing data. External marker motion data acquired from respiratory-gated radiotherapy patients were used to build and test the framework for robust optimization. The motion trajectories recorded during radiation treatment itself are not strictly necessary to generate the initial version of a robust treatment plan, but can be used to adapt the plan during the course of treatment. Single-field IMRT plans were optimized to deliver a uniform dose to a rectangular area. During delivery on a linear accelerator, a computer-driven motion phantom reproduced the patients' breathing patterns and a two-dimensional ionization detector array measured the dose delivered. The dose distributions from robust-optimized plans were compared to those from standard plans, which used a margin expansion. Dosimetric tests confirmed the improved sparing of the non-target area with robust planning, which was achieved without compromising the target coverage. The maximum dose in robust plans did not exceed 110% of the prescription, while the minimum target doses were comparable in standard and robust plans. In test courses, optimized for a simplified target geometry, and delivered to a phantom that moved in one dimension with an average amplitude of 17 mm, the robust treatment design produced a reduction of more than 12% of the integral dose to non-target areas, compared to the standard plan using 10 mm margin expansion. C1 [Vrancic, Christian] Univ Heidelberg, Mannheim Med Ctr, Dept Radiat Oncol, D-6800 Mannheim, Germany. [Trofimov, Alexei; Sharp, Gregory C.; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Trofimov, Alexei; Sharp, Gregory C.; Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chan, Timothy C. Y.] MIT, Ctr Operat Res, Cambridge, MA 02139 USA. RP Vrancic, C (reprint author), Univ Heidelberg, Mannheim Med Ctr, Dept Radiat Oncol, D-6800 Mannheim, Germany. EM cvrancic@ix.urz.uni-heidelberg.de FU US National Cancer Institute [RO1-CA118200]; United States-Israel Binational Science Foundation [2003275] FX This work was supported by the US National Cancer Institute under grant RO1-CA118200 and the United States-Israel Binational Science Foundation grant 2003275. CV was supported by Landestiftung Baden-Wurttemberg and the University of Heidelberg through the student practical training program. The authors thank Dr Steve B Jiang for assistance with the motion phantom. NR 27 TC 7 Z9 7 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 7 PY 2009 VL 54 IS 9 BP 2901 EP 2914 DI 10.1088/0031-9155/54/9/021 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 435NJ UT WOS:000265350300021 PM 19384003 ER PT J AU Roodman, GD AF Roodman, G. David TI Osteoclasts Pump Iron SO CELL METABOLISM LA English DT Editorial Material ID DEFICIENCY AB Osteoclasts are the primary cells that resorb bone; they require high energy levels to degrade bone matrix, releasing minerals to maintain calcium homeostasis. Recent work on osteoclast differentiation and activity highlights an important role for mitochondrial biogenesis and explores the role of iron transferrin in generating a positive osteoclastogenic feedback loop. C1 [Roodman, G. David] Vet Affairs Pittsburgh Healthcare Syst, Dept Med Hematol Oncol, Pittsburgh, PA 15240 USA. [Roodman, G. David] Univ Pittsburgh, Dept Med Hematol Oncol, Pittsburgh, PA 15260 USA. RP Roodman, GD (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Dept Med Hematol Oncol, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu NR 6 TC 6 Z9 6 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAY 6 PY 2009 VL 9 IS 5 BP 405 EP 406 DI 10.1016/j.cmet.2009.04.005 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 442LC UT WOS:000265841700004 PM 19416710 ER PT J AU Wang, XL Suzuki, R Lee, K Tran, T Gunton, JE Saha, AK Patti, ME Goldfine, A Ruderman, NB Gonzalez, FJ Kahn, CR AF Wang, Xiaohui L. Suzuki, Ryo Lee, Kevin Tran, Thien Gunton, Jenny E. Saha, Asish K. Patti, Mary-Elizabeth Goldfine, Allison Ruderman, Neil B. Gonzalez, Frank J. Kahn, C. Ronald TI Ablation of ARNT/HIF1 beta in Liver Alters Gluconeogenesis, Lipogenic Gene Expression, and Serum Ketones SO CELL METABOLISM LA English DT Article ID ACTIVATED PROTEIN-KINASE; HYPOXIA-INDUCIBLE FACTOR-1; ARYL-HYDROCARBON RECEPTOR; HEPATIC GLUCONEOGENESIS; INSULIN-RESISTANCE; LIPID HOMEOSTASIS; MALONYL-COA; PPAR-ALPHA; IN-VIVO; ACID AB We have previously shown that expression of the transcription factor ARNT/HIF1 beta is reduced in islets of humans with type 2 diabetes. We have now found that ARNT is also reduced in livers of diabetics. To study the functional effect of its reduction, we created mice with liver-specific ablation (L-ARNT KO) using ARNT IoxP mice and adenoviral-mediated delivery of Cre. L-ARNT KO mice had normal blood glucose but increased fed insulin levels. These mice also exhibited features of type 2 diabetes with increased hepatic gluconeogenesis, increased lipogenic gene expression, and low serum beta-hydroxybutyrate. These effects appear to be secondary to increased expression of CCAAT/enhancer-binding protein alpha (C/EBP alpha), farnesoid X receptor (FXR), and sterol response element-binding protein 1 c (SREBP-1c) and a reduction in phosphorylation of AMPK without changes in the expression of enzymes in ketogenesis, fatty acid oxidation, or FGF21. These results demonstrate that a deficiency of ARNT action in the liver, coupled with that in beta cells, could contribute to the metabolic phenotype of human type 2 diabetes. C1 [Wang, Xiaohui L.; Suzuki, Ryo; Lee, Kevin; Tran, Thien; Gunton, Jenny E.; Patti, Mary-Elizabeth; Goldfine, Allison; Kahn, C. Ronald] Harvard Univ, Joslin Diabet Ctr, Sch Med, Boston, MA 02215 USA. [Saha, Asish K.; Ruderman, Neil B.] Boston Med Ctr, Diabet Unit, Endocrinol Sect, Boston, MA 02118 USA. [Saha, Asish K.; Ruderman, Neil B.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Saha, Asish K.; Ruderman, Neil B.] Boston Univ, Sch Med, Dept Physiol, Boston, MA 02118 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. [Gunton, Jenny E.] Garvan Inst Med Res, Sydney, NSW, Australia. RP Kahn, CR (reprint author), Harvard Univ, Joslin Diabet Ctr, Sch Med, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu OI Saha, Asish/0000-0003-1001-5110; Ruderman, Neil/0000-0002-6589-6587 FU Intramural NIH HHS [Z01 BC005708-17]; NHLBI NIH HHS [P01 HL068758, P01HL68758]; NIDDK NIH HHS [R01 DK067509, DK-067509, R01 DK060837, DK-060837] NR 33 TC 42 Z9 42 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAY 6 PY 2009 VL 9 IS 5 BP 428 EP 439 DI 10.1016/j.cmet.2009.04.001 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 442LC UT WOS:000265841700007 PM 19416713 ER PT J AU Abdelmohsen, K Srikantan, S Yang, XL Lal, A Kim, HH Kuwano, Y Galban, S Becker, KG Kamara, D de Cabo, R Gorospe, M AF Abdelmohsen, Kotb Srikantan, Subramanya Yang, Xiaoling Lal, Ashish Kim, Hyeon Ho Kuwano, Yuki Galban, Stefanie Becker, Kevin G. Kamara, Davida de Cabo, Rafael Gorospe, Myriam TI Ubiquitin-mediated proteolysis of HuR by heat shock SO EMBO JOURNAL LA English DT Article DE post-transcriptional gene regulation; proteasome; protein stability; ribonucleoprotein complex; ubiquitination ID MESSENGER-RNA STABILITY; BINDING PROTEIN HUR; TRANSLATIONAL CONTROL; NUCLEAR IMPORT; STABILIZATION; TURNOVER; EXPRESSION; STRESS; PHOSPHORYLATION; KINASE AB The RNA-binding protein HuR regulates the stability and translation of numerous mRNAs encoding stress-response and proliferative proteins. Although its post-transcriptional influence has been linked primarily to its cytoplasmic translocation, here we report that moderate heat shock (HS) potently reduces HuR levels, thereby altering the expression of HuR target mRNAs. HS did not change HuR mRNA levels or de novo translation, but instead reduced HuR protein stability. Supporting the involvement of the ubiquitin-proteasome system in this process were results showing that (1) HuR was ubiquitinated in vitro and in intact cells, (2) proteasome inhibition increased HuR abundance after HS, and (3) the HuR kinase checkpoint kinase 2 protected against the loss of HuR by HS. Within a central, HS-labile similar to 110-amino-acid region, K182 was found to be essential for HuR ubiquitination and proteolysis as mutant HuR(K182R) was left virtually un-ubiquitinated and was refractory to HS-triggered degradation. Our findings reveal that HS transiently lowers HuR by proteolysis linked to K182 ubiquitination and that HuR reduction enhances cell survival following HS. The EMBO Journal (2009) 28, 1271-1282. doi: 10.1038/emboj.2009.67; Published online 26 March 2009 C1 [Abdelmohsen, Kotb; Srikantan, Subramanya; Yang, Xiaoling; Lal, Ashish; Kim, Hyeon Ho; Kuwano, Yuki; Galban, Stefanie; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. [Abdelmohsen, Kotb; Becker, Kevin G.] NIA, Res Resources Branch, IRP, NIH, Baltimore, MD 21224 USA. [Kamara, Davida; de Cabo, Rafael] NIA, Lab Expt Gerontol, IRP, NIH, Baltimore, MD 21224 USA. [Lal, Ashish] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Lal, Ashish] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Abdelmohsen, K (reprint author), NIA, Cellular & Mol Biol Lab, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM abdelmohsenk@grc.nia.nih.gov; myriam-gorospe@nih.gov RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810; Becker, Kevin/0000-0002-6794-6656; , rafael/0000-0003-2830-5693 FU NIA-IRP Program [Z01-AG000511-10]; NIA-IRP, NIH FX We thank MJ Pazin, V Dixit, WH Wood 3rd, B Frank, S Subaran, and FE Indig for their assistance with these studies. HCT116 cells were kindly provided by F Bunz. This research was supported entirely by the NIA-IRP Program Z01-AG000511-10 and by set-aside funds of the NIA-IRP, NIH. NR 55 TC 68 Z9 69 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 6 PY 2009 VL 28 IS 9 BP 1271 EP 1282 DI 10.1038/emboj.2009.67 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 443BK UT WOS:000265885000009 PM 19322201 ER PT J AU Kertesz, SG Weiner, SJ AF Kertesz, Stefan G. Weiner, Saul J. TI Housing the Chronically Homeless High Hopes, Complex Realities SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HEALTH-CARE; ALCOHOL; COHORT C1 [Kertesz, Stefan G.] Univ Alabama, Div Prevent Med, Birmingham Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL 35294 USA. [Weiner, Saul J.] Univ Illinois, Vet Affairs Ctr Management Complex Chron Care, Jesse Brown Vet Affairs Med Ctr Med & Pediat, Chicago, IL USA. RP Kertesz, SG (reprint author), Univ Alabama, Div Prevent Med, Birmingham Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit, 1530 3rd Ave S,MT608, Birmingham, AL 35294 USA. EM skertesz@uab.edu OI Kertesz, Stefan/0000-0001-6101-8421 NR 15 TC 34 Z9 34 U1 3 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 6 PY 2009 VL 301 IS 17 BP 1822 EP 1824 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 441AU UT WOS:000265742500036 PM 19417203 ER PT J AU Gordon, GJ Dong, LS Yeap, BY Richards, WG Glickman, JN Edenfield, H Mani, M Colquitt, R Maulik, G Van Oss, B Sugarbaker, DJ Bueno, R AF Gordon, Gavin J. Dong, Lingsheng Yeap, Beow Y. Richards, William G. Glickman, Jonathan N. Edenfield, Heather Mani, Madhubalan Colquitt, Richard Maulik, Gautam Van Oss, Branden Sugarbaker, David J. Bueno, Raphael TI Four-Gene Expression Ratio Test for Survival in Patients Undergoing Surgery for Mesothelioma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MALIGNANT PLEURAL MESOTHELIOMA; GENE-EXPRESSION; BREAST-CANCER; MICROARRAY DATA; MULTIMODALITY THERAPY; PROFILING DATA; PLEURECTOMY/DECORTICATION; CLASSIFICATION; CISPLATIN; RESECTION AB Malignant pleural mesothelioma has few effective treatments, one being cytoreductive surgery. We previously developed a gene ratio test to predict outcome of malignant pleural mesothelioma patients undergoing surgery. In this study, we investigated the predictive value and technical assay performance of this test in patients with malignant pleural mesothelioma. Clinical data were obtained prospectively from 120 consecutive patients with malignant pleural mesothelioma who were scheduled for debulking surgery at one institution. Specimens were obtained at surgery or by pleural biopsy examination. Expression data for four genes were collected from tumor specimens, and three ratios of gene expression (TM4SF1/PKM2, TM4SF1/ARHGDIA, and COBLL1/ARHGDIA) were determined by quantitative reverse transcriptase-polymerase chain reaction. Patients were assigned to good or poor outcome groups by the gene ratio test. Survival was estimated by the Kaplan-Meier method and the log-rank test in univariate analyses. A multivariable Cox proportional hazards model was used to control for prognostic factors. Technical robustness was determined by using up to 30 specimens per patient, two biopsy techniques, and two performance sites. All statistical tests were two-sided. The test predicted overall survival (P < .001) and cancer-specific survival (P = .007) in univariate analysis and overall survival in multivariable analysis (hazard ratio for death = 2.09, 95% confidence interval [CI] = 1.27 to 3.45, P = .004). The test was reproducible within patients and repeatable between two determinations for specimens with widely varying tumor cell contents. Repeatability between two determinations was 88.5% (95% CI = 84.0% to 92.2%) or, when technically unacceptable test values were excluded, 91.9% (95% CI = 87.4% to 95.1%). Reproducibility between two determinations was 96.1% (95% CI = 86.5% to 99.5%). Combining the gene ratio test and other prognostic factors allowed prospective discrimination between patients at high risk (median survival = 6.9 months, 95% CI = 2.6 to 8.9 months; 3-year survival = 0%) and low risk (median survival = 31.9 months, 95% CI = 21.9 to 41.7 months; 3-year survival = 42%). The gene ratio test for survival of patients with malignant pleural mesothelioma has robust predictive value and technical assay performance. C1 [Gordon, Gavin J.; Dong, Lingsheng; Richards, William G.; Edenfield, Heather; Mani, Madhubalan; Colquitt, Richard; Maulik, Gautam; Van Oss, Branden; Sugarbaker, David J.; Bueno, Raphael] Harvard Univ, Dept Surg, Div Thorac Surg, Sch Med, Boston, MA 02115 USA. [Glickman, Jonathan N.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Bueno, R (reprint author), Harvard Univ, Dept Surg, Div Thorac Surg, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM rbueno@partners.org FU National Cancer Institute [100315, 120528]; International Mesothelioma Program; Maurice Favell Fund FX National Cancer Institute (100315 and 120528 to R. B.) as well as grants from the International Mesothelioma Program at Brigham and Women's Hospital (to R. B.) and the Maurice Favell Fund at the Vancouver Foundation (to R. B.). NR 33 TC 42 Z9 42 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 6 PY 2009 VL 101 IS 9 BP 678 EP 686 DI 10.1093/jnci/djp061 PG 9 WC Oncology SC Oncology GA 444AR UT WOS:000265952700011 PM 19401544 ER PT J AU Garcia-Alloza, M Subramanian, M Thyssen, D Borrelli, LA Fauq, A Das, P Golde, TE Hyman, BT Bacskai, BJ AF Garcia-Alloza, Monica Subramanian, Meenakshi Thyssen, Diana Borrelli, Laura A. Fauq, Abdul Das, Pritam Golde, Todd E. Hyman, Bradley T. Bacskai, Brian J. TI Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the gamma-secretase inhibitor LY-411575 SO MOLECULAR NEURODEGENERATION LA English DT Article ID TRANSGENIC MOUSE MODEL; AMYLOID-BETA-PROTEIN; ALZHEIMERS-DISEASE; IN-VIVO; A-BETA; CEREBROSPINAL-FLUID; MULTIPHOTON MICROSCOPY; TG2576 MOUSE; PLASMA; BRAIN AB The gamma-secretase complex is a major therapeutic target for the prevention and treatment of Alzheimer's disease. Previous studies have shown that treatment of young APP mice with specific inhibitors of gamma-secretase prevented formation of new plaques. It has not yet been shown directly whether existing plaques would be affected by gamma-secretase inhibitor treatment. Similarly, alterations in neuronal morphology in the immediate vicinity of plaques represent a plaque-specific neurotoxic effect. Reversal of these alterations is an important endpoint of successful therapy whether or not a treatment affects plaque size. In the present study we used longitudinal imaging in vivo with multiphoton microscopy to study the effects of the orally active gamma-secretase inhibitor LY-411575 in 10-11 month old APP:PS1 mice with established amyloid pathology and neuritic abnormalities. Neurons expressed YFP allowing fluorescent detection of morphology whereas plaques were labelled with methoxy-XO4. The same identified neurites and plaques were followed in weekly imaging sessions in living mice treated daily (5 mg/kg) for 3 weeks with the compound. Although LY-411575 reduced A beta levels in plasma and brain, it did not have an effect on the size of existing plaques. There was also no effect on the abnormal neuritic curvature near plaques, or the dystrophies in very close proximity to senile plaques. Our results suggest that therapeutics aimed at inhibition of A beta generation are less effective for reversal of existing plaques than for prevention of new plaque formation and have no effect on the plaque-mediated neuritic abnormalities, at least under these conditions where A beta production is suppressed but not completely blocked. Therefore, a combination therapy of A beta suppression with agents that increase clearance of amyloid and/or prevent neurotoxicity might be needed for a more effective treatment in patients with pre-existing pathology. C1 [Garcia-Alloza, Monica; Subramanian, Meenakshi; Thyssen, Diana; Borrelli, Laura A.; Hyman, Bradley T.; Bacskai, Brian J.] Massachusetts Gen Hosp, Massgen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Garcia-Alloza, Monica; Fauq, Abdul] Univ Cadiz, Fac Med, Area Fisiol, Cadiz 11003, Spain. [Das, Pritam; Golde, Todd E.] Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL 32224 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Massgen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM mogarcia3344@yahoo.es; psminakshi@gmail.com; dianathyssen@gmail.com; laborrelli@partners.org; fauq.abdul@mayo.edu; das.pritam@mayo.edu; golde.todd@mayo.edu; bhyman@partners.org; bbacskai@partners.org OI Garcia-Alloza, Monica/0000-0003-1610-4114 FU NIH [AG020570, EB000768, AG08487, AG025531]; AHA-Bugher Foundation; Ramon y Cajal FX This work was supported by NIH AG020570, EB000768, AG08487, AG025531, and a fellowship from the AHA-Bugher Foundation and Ramon y Cajal contract (MG-A). NR 50 TC 33 Z9 33 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1750-1326 J9 MOL NEURODEGENER JI Mol. Neurodegener. PD MAY 6 PY 2009 VL 4 AR 19 DI 10.1186/1750-1326-4-19 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 461GJ UT WOS:000267252400001 PM 19419556 ER PT J AU de Gelder, B Partan, S AF de Gelder, Beatrice Partan, Sarah TI The neural basis of perceiving emotional bodily expressions in monkeys SO NEUROREPORT LA English DT Article DE body; emotion; functional magnetic resonance imaging; monkey; threat ID HUMAN EXTRASTRIATE CORTEX; SURFACE-BASED ANALYSIS; TEMPORAL CORTEX; CEREBRAL-CORTEX; FUNCTIONAL MRI; BODY LANGUAGE; FACES; REPRESENTATIONS; MOTION; SYSTEM AB Higher animals invest considerable time and brain resources in monitoring each others' body language. A network of dedicated brain structures is presumably involved in social perception. We hypothesized that functional magnetic resonance imaging may reveal portions of inferior temporal cortex participating in processing social signals. We used contrast agent-enhanced awake monkey functional magnetic resonance imaging to test whether subdivisions of inferior temporal cortex are sensitive to emotional body displays of conspecifics, and whether the degree of activation reflects the social intention expressed. We show that portions of superior temporal sulcus play a central role in processing body images of conspecifics and that these areas are preferentially sensitive to threat signals indicating that threat may be the most salient social signal. NeuroReport 20:642-646 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [de Gelder, Beatrice] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Partan, Sarah] New Hampshire Coll, Amherst, NH USA. [de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. RP de Gelder, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Room 409,Bldg 36,1st St, Charlestown, MA 02129 USA. EM degelder@nmr.mgh.harvard.edu FU Human Frontier Science Program [HFSP-RGP0054/2004-C]; Dutch Science Organization (NWO); N.C.R.R. [P41RR14075]; MIND Institute FX Authors gratefully acknowledge the contribution of J. Arsenault and W. Vanduffel who performed the scanning and data analysis. B.dG. was partly supported by the Human Frontier Science Program HFSP-RGP0054/2004-C and a grant from the Dutch Science Organization (NWO). The Martinos Center is supported by N.C.R.R. grant P41RR14075 and the MIND Institute. The authors report no conflict of interest. NR 25 TC 11 Z9 11 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 6 PY 2009 VL 20 IS 7 BP 642 EP 646 DI 10.1097/WNR.0b013e32832a1e56 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 442VN UT WOS:000265868800002 PM 19349919 ER PT J AU Kidambi, S Yarmush, J Fong, W Kamath, S SchianodiCola, J Nahmias, Y AF Kidambi, Srivatsan Yarmush, Joel Fong, Wayne Kamath, Sangeetha SchianodiCola, Joseph Nahmias, Yaakov TI Propofol induces ERK-dependant expression of c-Fos and Egr-1 in neuronal cells SO NEUROREPORT LA English DT Article DE gamma-aminobutyric acid; extracellular signal-regulated kinase; immediate early genes; propofol ID IMMEDIATE-EARLY GENES; RAT HIPPOCAMPAL SLICES; LONG-TERM POTENTIATION; PROTEIN-KINASES; ACTIVATION; MEMORY; PHOSPHORYLATION; ANESTHETICS; ISOFLURANE AB This study explored the effects of propofol on c-Fos and Egr-1 in neuroblastoma (N2A) cells. We demonstrate that propofol induced the expression of c-Fos and Egr-1 within 30 and 60 min of exposure time. At 16.8 mu M concentration, propofol induced a 6 and 2.5-fold expression of c-Fos and Egr-1, respectively. However, at concentrations above 100 mu M, propofol failed to induce expression of c-Fos or Egr-1. Propofol-induced c-Fos and Egr-1 transcription was unaffected by bicuculline, a gamma-aminobutyric acid-A receptor antagonist, but was abolished by PD98059, a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor. Our study shows that clinically relevant concentrations of propofol induce c-Fos and Egr-1 expression through an extracellular signal-regulated kinase mediated and gamma-aminobutyric acid-A independent pathway. NeuroReport 20:657-662 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Kidambi, Srivatsan; Yarmush, Joel; Fong, Wayne; Kamath, Sangeetha; SchianodiCola, Joseph] New York Methodist Hosp, Dept Anesthesiol, Brooklyn, NY USA. [Kidambi, Srivatsan; Nahmias, Yaakov] Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA USA. [Kidambi, Srivatsan; Nahmias, Yaakov] Harvard Univ, Sch Med, Boston, MA USA. RP Nahmias, Y (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, 114 16th St,Room 2450, Charlestown, MA 02129 USA. EM srivatsan.kidambi@gmail.com; ynahmias@partners.org RI Nahmias, Yaakov/H-4725-2013; KIDAMBI, SRIVATSAN/A-5689-2015; OI KIDAMBI, SRIVATSAN/0000-0002-0282-0411; Nahmias, Yaakov/0000-0002-6051-616X FU NIH/NIDDK [K01DK090241]; Park Slope Anesthesia Associates FX The authors thank Dr Martin Yarmush for valuable discussions regarding the manuscript. We also thank Dr Monica Casali for her valuable suggestions regarding PCR experiments. This study was supported by NIH/NIDDK Grant K01DK090241, by Park Slope Anesthesia Associates, and by the core facilities of Shriners Childrens Hospital. NR 23 TC 3 Z9 6 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 6 PY 2009 VL 20 IS 7 BP 657 EP 662 DI 10.1097/WNR.0b013e328329a449 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 442VN UT WOS:000265868800005 PM 19349923 ER PT J AU Salthouse, CD Reynolds, F Tam, JM Josephson, L Mahmood, U AF Salthouse, Christopher D. Reynolds, Fred Tam, Jenny M. Josephson, Lee Mahmood, Urnar TI Quantitative measurement of protease activity with correction of probe delivery and tissue absorption effects SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article DE Fluorescence imaging; Fluorescence lifetime; Activatable probe; Ratiometric ID CANCER AB Proteases play important roles in a variety of pathologies front heart disease to cancer. Quantitative measurement of protease activity is possible using a novel spectrally matched dual fluorophore probe and a small animal lifetime imager. The recorded fluorescence from an activatable fluorophore, one that changes its fluorescent amplitude after biological target interaction, is also influenced by other factors including imaging probe delivery and optical tissue absorption of excitation and emission light, Fluorescence from a second spectrally matched constant (non-activatable) fluorophore oil each nanoparticle platform call be used to correct for both probe delivery and tissue absorption. The fluorescence from each fluorophore is separated using fluorescence lifetime methods. (C) 2009 Elsevier B.V. All rights reserved. C1 [Salthouse, Christopher D.; Reynolds, Fred; Tam, Jenny M.; Josephson, Lee; Mahmood, Urnar] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Josephson, Lee; Mahmood, Urnar] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5406, Charlestown, MA 02129 USA. EM mahmood@helix.mgh.harvard.edu FU NIH [R01EB001872]; Vivo Multichannel Fluorescence Imaging [T32EB002102]; Postgraduate Program in Radiological Sciences FX This work was supported by NIH grants R01EB001872 "in Vivo Multichannel Fluorescence Imaging" and T32EB002102 "Postgraduate Program in Radiological Sciences". NR 17 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0925-4005 J9 SENSOR ACTUAT B-CHEM JI Sens. Actuator B-Chem. PD MAY 6 PY 2009 VL 138 IS 2 BP 591 EP 597 DI 10.1016/j.snb.2009.02.037 PG 7 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 443EU UT WOS:000265893800031 PM 20161242 ER PT J AU Pei, XH Bai, F Smith, MD Usary, J Fan, C Pai, SY Ho, IC Perou, CM Xiong, Y AF Pei, Xin-Hai Bai, Feng Smith, Matthew D. Usary, Jerry Fan, Cheng Pai, Sung-Yun Ho, I-Cheng Perou, Charles M. Xiong, Yue TI CDK Inhibitor p18(INK4c) Is a Downstream Target of GATA3 and Restrains Mammary Luminal Progenitor Cell Proliferation and Tumorigenesis SO CANCER CELL LA English DT Article ID GENE-EXPRESSION SIGNATURE; HUMAN BREAST-TUMORS; STEM-CELL; CYCLIN D1; MOLECULAR PORTRAITS; CANCER; GLAND; P16(INK4A); MICE; DIFFERENTIATION AB Mammary epithelia are composed of luminal and myoepithelial/basal cells whose neoplastic transformations lead to distinct types of breast cancers with diverse clinical features. We report that mice deficient for the CDK4/6 inhibitor p18(Ink4c) spontaneously develop ER-positive luminal tumors at a high penetrance. Ink4c deletion stimulates luminal progenitor cell proliferation at pubertal age and maintains an expanded luminal progenitor cell population throughout life. We demonstrate that GATA3 binds to and represses INK4C transcription. In human breast cancers, low INK4C and high GATA3 expressions are simultaneously observed in luminal A type tumors and predict a favorable patient outcome. Hence, p18(INK4c) is a downstream target of GATA3, constrains luminal progenitor cell expansion, and suppresses luminal tumorigenesis in the mammary gland. C1 [Pei, Xin-Hai; Bai, Feng; Smith, Matthew D.; Usary, Jerry; Fan, Cheng; Perou, Charles M.; Xiong, Yue] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Perou, Charles M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Xiong, Yue] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. [Perou, Charles M.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. [Ho, I-Cheng] Harvard Univ, Sch Med, Dept Pediat Hematol Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ho, I-Cheng] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Xiong, Y (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM yxiong@email.unc.edu RI Pei, Xin-Hai/P-1812-2014; OI Perou, Charles/0000-0001-9827-2247 FU NCI Breast SPORE program [P50-CA58223]; Breast Cancer Research Foundation; NIH [CA68377] FX We thank Yojiro Kotake for helping with the ChIP assay and Ned Sharpless, Chuxia Deng, and Connie Eaves for discussions. F.B. was supported in part by a U.S. Department of Defense Career Postdoctoral fellowship. This study was supported by the NCI Breast SPORE program (P50-CA58223) and the Breast Cancer Research Foundation grants (to C.M.P.), and by an NIH grant (CA68377, to Y.X.). NR 48 TC 48 Z9 52 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY 5 PY 2009 VL 15 IS 5 BP 389 EP 401 DI 10.1016/j.ccr.2009.03.004 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 443IK UT WOS:000265903200007 PM 19411068 ER PT J AU Belkin, M Bhatt, DL AF Belkin, Michael Bhatt, Deepak L. TI Carotid Stenting in the Elderly Is 80 the New 60? SO CIRCULATION LA English DT Editorial Material DE carotid arteries; stenosis ID HIGH-RISK PATIENTS; ARTERY STENOSIS; ENDARTERECTOMY; PREVENTION; TRIAL C1 [Belkin, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Belkin, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mbelkin@partners.org NR 19 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 5 PY 2009 VL 119 IS 17 BP 2302 EP 2304 DI 10.1161/CIRCULATIONAHA.109.857532 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 441PF UT WOS:000265780400003 PM 19414655 ER PT J AU Hoffmann, U Bamberg, F Chae, CU Nichols, JH Rogers, IS Seneviratne, SK Truong, QA Cury, RC Abbara, S Shapiro, MD Moloo, J Butler, J Ferencik, M Lee, H Jang, IK Parry, BA Brown, DF Udelson, JE Achenbach, S Brady, TJ Nagurney, JT AF Hoffmann, Udo Bamberg, Fabian Chae, Claudia U. Nichols, John H. Rogers, Ian S. Seneviratne, Sujith K. Truong, Quynh A. Cury, Ricardo C. Abbara, Suhny Shapiro, Michael D. Moloo, Jamaluddin Butler, Javed Ferencik, Maros Lee, Hang Jang, Ik-Kyung Parry, Blair A. Brown, David F. Udelson, James E. Achenbach, Stephan Brady, Thomas J. Nagurney, John T. TI Coronary Computed Tomography Angiography for Early Triage of Patients With Acute Chest Pain The ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE cardiac CT; emergency department; acute chest pain ID EMERGENCY-DEPARTMENT PATIENTS; ACUTE CARDIAC ISCHEMIA; ARTERY-DISEASE; PRACTICAL IMPLEMENTATION; INTRAVASCULAR ULTRASOUND; RISK STRATIFICATION; PROGNOSTIC VALUE; UNSTABLE ANGINA; PERFUSION; GUIDELINES AB Objectives This study was designed to determine the usefulness of coronary computed tomography angiography (CTA) in patients with acute chest pain. Background Triage of chest pain patients in the emergency department remains challenging. Methods We used an observational cohort study in chest pain patients with normal initial troponin and nonischemic electrocardiogram. A 64-slice coronary CTA was performed before admission to detect coronary plaque and stenosis (> 50% luminal narrowing). Results were not disclosed. End points were acute coronary syndrome (ACS) during index hospitalization and major adverse cardiac events during 6-month follow-up. Results Among 368 patients (mean age 53 +/- 12 years, 61% men), 31 had ACS (8%). By coronary CTA, 50% of these patients were free of coronary artery disease (CAD), 31% had nonobstructive disease, and 19% had inconclusive or positive computed tomography for significant stenosis. Sensitivity and negative predictive value for ACS were 100% (n = 183 of 368; 95% confidence interval [CI]: 98% to 100%) and 100% ( 95% CI: 89% to 100%), respectively, with the absence of CAD and 77% (95% CI: 59% to 90%) and 98% ( n = 300 of 368, 95% CI: 95% to 99%), respectively, with significant stenosis by coronary CTA. Specificity of presence of plaque and stenosis for ACS were 54% ( 95% CI: 49% to 60%) and 87% (95% CI: 83% to 90%), respectively. Only 1 ACS occurred in the absence of calcified plaque. Both the extent of coronary plaque and presence of stenosis predicted ACS independently and incrementally to Thrombolysis In Myocardial Infarction risk score (area under curve: 0.88, 0.82, vs. 0.63, respectively; all p < 0.0001). Conclusions Fifty percent of patients with acute chest pain and low to intermediate likelihood of ACS were free of CAD by computed tomography and had no ACS. Given the large number of such patients, early coronary CTA may significantly improve patient management in the emergency department. (J Am Coll Cardiol 2009; 53: 1642-50) (C) 2009 by the American College of Cardiology Foundation C1 [Hoffmann, Udo; Bamberg, Fabian; Nichols, John H.; Rogers, Ian S.; Seneviratne, Sujith K.; Truong, Quynh A.; Cury, Ricardo C.; Abbara, Suhny; Shapiro, Michael D.; Moloo, Jamaluddin; Butler, Javed; Ferencik, Maros; Brady, Thomas J.] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Hoffmann, Udo; Bamberg, Fabian; Cury, Ricardo C.; Abbara, Suhny; Brady, Thomas J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Chae, Claudia U.; Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Parry, Blair A.; Brown, David F.; Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA. [Udelson, James E.] Tufts Med Ctr, Div Cardiol, Boston, MA USA. [Udelson, James E.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Achenbach, Stephan] Univ Erlangen Nurnberg, Dept Cardiol, Erlangen, Germany. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org FU National Institutes of Health [R01 HL080053, T32HL076136]; Siemens Medical Solutions; GE Healthcare; Bracco; Ezem; Siemens; Partners Imaging; Magellan Health; Perceptive Informatics; Bayer Schering Pharma; Biosite for a biomarker research study FX This work was supported by the National Institutes of Health (R01 HL080053) and in part supported by Siemens Medical Solutions and GE Healthcare. Drs. Rogers, Truong, Shapiro, and Moloo were supported by the National Institutes of Health grant T32HL076136. Dr. Hoffmann has received research grants from GE Healthcare and Siemens. Dr. Abbara has received research funding from Bracco and consulting honoraria (minor) from Ezem, Siemens, Partners Imaging, Magellan Health, Perceptive Informatics. Dr. Achenbach has received grant support from Siemens and Bayer Schering Pharma. Dr. Nagurney is funded by Biosite for a biomarker research study. NR 41 TC 289 Z9 292 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 5 PY 2009 VL 53 IS 18 BP 1642 EP 1650 DI 10.1016/j.jacc.2009.01.052 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 439LL UT WOS:000265628500003 PM 19406338 ER PT J AU Das, G Choi, Y Sicinski, P Levine, EM AF Das, Gaurav Choi, Yoon Sicinski, Piotr Levine, Edward M. TI Cyclin D1 fine-tunes the neurogenic output of embryonic retinal progenitor cells SO NEURAL DEVELOPMENT LA English DT Article ID NUCLEAR RECEPTOR NR2E3; MOUSE RETINA; TRANSGENIC MICE; FATE DETERMINATION; HORIZONTAL CELLS; RAT RETINA; PHOTORECEPTOR DEGENERATION; VERTEBRATE RETINA; GLAND DEVELOPMENT; T-ANTIGEN AB Background: Maintaining the correct balance of proliferation versus differentiation in retinal progenitor cells (RPCs) is essential for proper development of the retina. The cell cycle regulator cyclin D1 is expressed in RPCs, and mice with a targeted null allele at the cyclin D1 locus (Ccnd1(-/-)) have microphthalmia and hypocellular retinas, the latter phenotype attributed to reduced RPC proliferation and increased photoreceptor cell death during the postnatal period. How cyclin D1 influences RPC behavior, especially during the embryonic period, is unclear. Results: In this study, we show that embryonic RPCs lacking cyclin D1 progress through the cell cycle at a slower rate and exit the cell cycle at a faster rate. Consistent with enhanced cell cycle exit, the relative proportions of cell types born in the embryonic period, such as retinal ganglion cells and photoreceptor cells, are increased. Unexpectedly, cyclin D1 deficiency decreases the proportions of other early born retinal neurons, namely horizontal cells and specific amacrine cell types. We also found that the laminar positioning of horizontal cells and other cell types is altered in the absence of cyclin D1. Genetically replacing cyclin D1 with cyclin D2 is not efficient at correcting the phenotypes due to the cyclin D1 deficiency, which suggests the D-cyclins are not fully redundant. Replacement with cyclin E or inactivation of cyclin-dependent kinase inhibitor p27Kip1 restores the balance of RPCs and retinal cell types to more normal distributions, which suggests that regulation of the retinoblastoma pathway is an important function for cyclin D1 during embryonic retinal development. Conclusion: Our findings show that cyclin D1 has important roles in RPC cell cycle regulation and retinal histogenesis. The reduction in the RPC population due to a longer cell cycle time and to an enhanced rate of cell cycle exit are likely to be the primary factors driving retinal hypocellularity and altered output of precursor populations in the embryonic Ccnd1(-/-) retina. C1 [Das, Gaurav; Levine, Edward M.] Univ Utah, Dept Ophthalmol & Visual Sci, John A Moran Eye Ctr, Salt Lake City, UT 84132 USA. [Das, Gaurav; Levine, Edward M.] Univ Utah, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA. [Choi, Yoon; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Choi, Yoon; Sicinski, Piotr] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Levine, EM (reprint author), Univ Utah, Dept Ophthalmol & Visual Sci, John A Moran Eye Ctr, Salt Lake City, UT 84132 USA. EM gaurav.das@hsc.utah.edu; yoon_choi@dfci.harvard.edu; peter_sicinski@dfci.harvard.edu; ed.levine@utah.edu RI Levine, Edward/N-3878-2015 OI Levine, Edward/0000-0003-1725-2805 FU NEI vision core [EY0014800]; Research to Prevent Blindness; Leukemia and Lymphoma Society.; [R01 grants EY013760]; [CA108950]; [CA083688] FX We thank Dr Sabine Fuhrmann for critical reading of the manuscript and members of the Levine and Fuhrmann laboratories for their insights and assistance. We also thank Drs Nadean Brown, Helena Edlund, Alejandro Sanchez-Alvarado, and Anand Swaroop for reagents and advice. The ISLI and PAX6 monoclonal antibodies, developed by Drs TM Jessell and A Kawakami, respectively, were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA, USA. This work was supported by R01 grants EY013760 ( EML), CA108950 (PS), and CA083688 (PS), by NEI vision core grant EY0014800, and unrestricted funding by Research to Prevent Blindness to the Moran Eye Center. EML is a Research to Prevent Blindness Sybil Harrington Scholar and PS is a Fellow of the Leukemia and Lymphoma Society. NR 95 TC 27 Z9 27 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1749-8104 J9 NEURAL DEV JI Neural Dev. PD MAY 5 PY 2009 VL 4 AR 15 DI 10.1186/1749-8104-4-15 PG 23 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 461ZN UT WOS:000267314400001 PM 19416500 ER PT J AU Fong, TG Jones, RN Shi, P Marcantonio, ER Yap, L Rudolph, JL Yang, FM Kiely, DK Inouye, SK AF Fong, T. G. Jones, R. N. Shi, P. Marcantonio, E. R. Yap, L. Rudolph, J. L. Yang, F. M. Kiely, D. K. Inouye, S. K. TI Delirium accelerates cognitive decline in Alzheimer disease SO NEUROLOGY LA English DT Article ID FUNCTIONAL DECLINE; PREVENT DELIRIUM; ELDERLY SUBJECTS; OLDER PATIENTS; DEMENTIA; INTERVENTION; ASSOCIATION; PROGRESSION; PROGNOSIS; DIAGNOSIS AB Objective: To examine the impact of delirium on the trajectory of cognitive function in a cohort of patients with Alzheimer disease (AD). Methods: A secondary analysis of data collected from a large prospective cohort, the Massachusetts Alzheimer's Disease Research Center's patient registry, examined cognitive performance over time in patients who developed (n = 72) or did not develop (n = 336) delirium during the course of their illnesses. Cognitive performance was measured by change in score on the Information-Memory-Concentration (IMC) subtest of the Blessed Dementia Rating Scale. Delirium was identified using a previously validated chart review method. Using linear mixed regression models, rates of cognitive change were calculated, controlling for age, sex, education, comorbid medical diagnoses, family history of dementia, dementia severity score, and duration of symptoms before diagnosis. Results: A significant acceleration in the slope of cognitive decline occurs following an episode of delirium. Among patients who developed delirium, the average decline at baseline for performance on the IMC was 2.5 points per year, but after an episode of delirium there was further decline to an average of 4.9 points per year (p = 0.001). Across groups, the rate of change in IMC score occurred about three times faster in those who had delirium compared to those who did not. Conclusions: Delirium can accelerate the trajectory of cognitive decline in patients with Alzheimer disease (AD). The information from this study provides the foundation for future randomized intervention studies to determine whether prevention of delirium might ameliorate or delay cognitive decline in patients with AD. Neurology (R) 2009;72:1570-1575 C1 [Fong, T. G.; Jones, R. N.; Shi, P.; Rudolph, J. L.; Yang, F. M.; Kiely, D. K.; Inouye, S. K.] Hebrew SeniorLife, Inst Aging Res, Aging Brain Ctr, Boston, MA 02131 USA. [Fong, T. G.] Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Marcantonio, E. R.; Inouye, S. K.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Yap, L.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rudolph, J. L.] Ctr Geriatr Res Educ & Clin, VA Boston Healthcare Syst, Boston, MA USA. [Yang, F. M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Rudolph, J. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA. RP Fong, TG (reprint author), Hebrew SeniorLife, Inst Aging Res, Aging Brain Ctr, 1200 Ctr St, Boston, MA 02131 USA. EM tfong@bidmc.harvard.edu RI Jones, Richard/J-3488-2013 OI Jones, Richard/0000-0002-1049-218X FU Massachusetts Alzheimer's Disease Research Center [P50AG005134]; National Institute on Aging [K23 AG 031320, R21 AG027549, R21 AG026566, R01 AG 030618, R03 AG 028189, R03 AG029861, K24AG000949, P60 AG008812]; Alzheimer's Association [IIRG-08-88737]; VA Rehabilitation Career Development Award FX Supported in part by a pilot grant from the Massachusetts Alzheimer's Disease Research Center (P50AG005134) and grants from the National Institute on Aging, K23 AG 031320 (T.G.F.), R21 AG027549 (E.R.M.), R21 AG026566 (E.R.M.), R01 AG 030618 (E.R.M.), R03 AG 028189 (E.R.M.), R03 AG029861 (J.L.R.), K24AG000949 (S.K.I.), P60 AG008812 (R.N.J.), Alzheimer's Association Grant #IIRG-08-88737 (S.K.I.), and VA Rehabilitation Career Development Award (J.L.R.). S.K.I. holds the Milton and Shirley F. Levy Family Chair. NR 30 TC 148 Z9 149 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAY 5 PY 2009 VL 72 IS 18 BP 1570 EP 1575 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 441PZ UT WOS:000265782600007 PM 19414723 ER PT J AU Athappilly, G Pelak, VS AF Athappilly, Geetha Pelak, Victoria S. TI Teaching NeuroImages: Superior segmental optic nerve hypoplasia confirmed by optical coherence tomography SO NEUROLOGY LA English DT Editorial Material C1 [Athappilly, Geetha; Pelak, Victoria S.] Univ Colorado, Sch Med, Dept Ophthalmol, Denver, CO USA. [Pelak, Victoria S.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO USA. [Pelak, Victoria S.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Pelak, VS (reprint author), 12631 E 17th Ave,POB 6511,Mail Stop B185, Aurora, CO 80045 USA. EM Victoria.Pelak@UCHSC.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 5 PY 2009 VL 72 IS 18 BP E91 EP E92 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 441PZ UT WOS:000265782600024 PM 19414718 ER PT J AU Adams, JC Seed, B Lu, N Landry, A Xavier, RJ AF Adams, J. C. Seed, B. Lu, N. Landry, A. Xavier, R. J. TI SELECTIVE ACTIVATION OF NUCLEAR FACTOR KAPPA B IN THE COCHLEA BY SENSORY AND INFLAMMATORY STRESS SO NEUROSCIENCE LA English DT Article ID INDUCED HEARING-LOSS; SPIRAL LIGAMENT FIBROCYTES; INNER-EAR; ACOUSTIC TRAUMA; NONSYNDROMIC DEAFNESS; IMMUNE-RESPONSES; DOWN-REGULATION; MICE; MOUSE; EXPRESSION AB Damage response pathways triggered by mechanical stress might reasonably be expected to be conserved throughout evolution. However, using a nuclear factor kappa B (NF-kappa B) reporter mouse we show here that this phylogenetically recent transcription factor plays a major role in the response to mechanosensory stress in the mammalian inner ear. The protective action of NF-kappa B is exerted in neither sensory nor non-sensory epithelial cells, but rather in connective tissue cells within the spiral ligament and spiral limbus. In the spiral ligament, predominantly type I fibrocytes are activated following noise exposure, whereas type II fibrocytes are activated following systemic inflammatory stress. Immune-mediated and acoustic trauma-mediated hearing loss syndromes in humans may in part result from the vulnerability of type II and type I fibrocytes to systemic inflammatory stress and acoustic trauma, respectively. Unexpected cell-specific and stress-specific NF-kappa B activation found in the inner ear in this in vivo study suggest that this approach may have wide applications in demonstrating similar specializations of stress responses in other tissues, including the brain. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Adams, J. C.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Seed, B.; Lu, N.; Landry, A.; Xavier, R. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Adams, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM joe_adams@meei.harvard.edu FU National Institutes of Health [DC03929, AI062773, DK043351, AI27849, AI46731] FX This work is supported by grants from the National Institutes of Health DC03929 to J.C.A. AI062773, DK043351 to R.J.X and AI27849, AI46731 to B.S. We thank Drs. Charles Liberman, Saumil Merchant, Ian Rosenberg and Joe Avruch for critical reading of the manuscript. We also thank Sarah McCaffrey for expert technical assistance. NR 52 TC 17 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD MAY 5 PY 2009 VL 160 IS 2 BP 530 EP 539 DI 10.1016/j.neuroscience.2009.02.073 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 436PQ UT WOS:000265426700027 PM 19285117 ER PT J AU Calvo, SE Pagliarini, DJ Mootha, VK AF Calvo, Sarah E. Pagliarini, David J. Mootha, Vamsi K. TI Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE polymorphism; post-transcriptional control; proteomics; translation; uORF ID COAGULATION-FACTOR-XII; EUKARYOTIC MESSENGER-RNAS; UCSC GENOME BROWSER; BETA-GLOBIN GENE; POSTTRANSCRIPTIONAL REGULATION; 5'-UNTRANSLATED REGION; STRUCTURAL FEATURES; VENOUS THROMBOSIS; MOUSE LUNG; MUTATIONS AB Upstream ORFs (uORFs) are mRNA elements defined by a start codon in the 5' UTR that is out-of-frame with the main coding sequence. Although uORFs are present in approximately half of human and mouse transcripts, no study has investigated their global impact on protein expression. Here, we report that uORFs correlate with significantly reduced protein expression of the downstream ORF, based on analysis of 11,649 matched mRNA and protein measurements from 4 published mammalian studies. Using reporter constructs to test 25 selected uORFs, we estimate that uORFs typically reduce protein expression by 30-80%, with a modest impact on mRNA levels. We additionally identify polymorphisms that alter uORF presence in 509 human genes. Finally, we report that 5 uORF-altering mutations, detected within genes previously linked to human diseases, dramatically silence expression of the downstream protein. Together, our results suggest that uORFs influence the protein expression of thousands of mammalian genes and that variation in these elements can influence human phenotype and disease. C1 [Calvo, Sarah E.; Pagliarini, David J.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Calvo, Sarah E.; Pagliarini, David J.; Mootha, Vamsi K.] MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA. [Calvo, Sarah E.; Pagliarini, David J.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Calvo, Sarah E.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-806, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu OI Pagliarini, Dave/0000-0002-0001-0087 FU National Institute of General Medical Science [GM077465] FX We thank S. E. Ong for advice on mass spectrometry; M. Garber for advice on alignments; O. Goldberger and Y. Kim for technical assistance; J. Dixon for technical resources; and D. Altshuler, J. Hirshhorn, M. Springer, D. Neafsey, B. Voight, S. Carter, J. Avruch, and E. Lander for comments on the manuscript and project. We thank the Broad Institute Sequencing Platform, Washington University Genome Sequencing Center (St. Louis, MO), and Baylor Human Genome Sequencing Center (Houston, TX) for the vertebrate genome sequences used in comparative analyses. This work was supported by National Institute of General Medical Science Grant GM077465 (to V. K. M.). NR 47 TC 270 Z9 273 U1 3 U2 22 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 5 PY 2009 VL 106 IS 18 BP 7507 EP 7512 DI 10.1073/pnas.0810916106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441QI UT WOS:000265783600045 PM 19372376 ER PT J AU Terrell, KM Hustey, FM Hwang, U Gerson, LW Wenger, NS Miller, DK AF Terrell, Kevin M. Hustey, Fredric M. Hwang, Ula Gerson, Lowell W. Wenger, Neil S. Miller, Douglas K. CA SAEM Geriatric Task Force TI Quality Indicators for Geriatric Emergency Care SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE emergency medical services; emergency service; hospital; geriatrics; health services for the aged; quality indicators; health care; quality of health care ID HIP FRACTURE PATIENTS; DEPARTMENT PATIENTS; ELDERLY EMERGENCY; COGNITIVE IMPAIRMENT; OLDER EMERGENCY; NURSING-HOMES; HEALTH-CARE; ACUTE PAIN; OF-CARE; TRANSITIONAL CARE AB Emergency departments (EDs), similar to other health care environments, are concerned with improving the quality of patient care. Older patients comprise a large, growing, and particularly vulnerable subset of ED users. The project objective was to develop ED-specific quality indicators for older patients to help practitioners identify quality gaps and focus quality improvement efforts. The Society for Academic Emergency Medicine (SAEM) Geriatric Task Force, including members representing the American College of Emergency Physicians (ACEP), selected three conditions where there are quality gaps in the care of older patients: cognitive assessment, pain management, and transitional care in both directions between nursing homes and EDs. For each condition, a content expert created potential quality indicators based on a systematic review of the literature, supplemented with expert opinion when necessary. The original candidate quality indicators were modified in response to evaluation by four groups: the Task Force, the SAEM Geriatric Interest Group, and audiences at the 2007 SAEM Annual Meeting and the 2008 American Geriatrics Society Annual Meeting. The authors offer 6 quality indicators for cognitive assessment, 6 for pain management, and 11 for transitions between nursing homes and EDs. These quality indicators will help researchers and clinicians target quality improvement efforts. The next steps will be to test the feasibility of capturing the quality indicators in existing medical records and to measure the extent to which each quality indicator is successfully met in current emergency practice. C1 [Terrell, Kevin M.] Indiana Univ, Sch Med, Dept Emergency Med, Indianapolis, IN USA. [Terrell, Kevin M.; Miller, Douglas K.] Indiana Univ, Sch Med, Ctr Aging Res, Indianapolis, IN USA. [Terrell, Kevin M.; Miller, Douglas K.] Indiana Univ, Sch Med, Regenstrief Inst, Indianapolis, IN USA. [Hustey, Fredric M.] Case Western Reserve Univ, Dept Emergency Med, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Hwang, Ula] Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, Dept Emergency Med, New York, NY USA. [Hwang, Ula] James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Gerson, Lowell W.] Northeastern Ohio Univ Coll Med & Pharm, Dept Community Hlth Sci, Akron, OH USA. [Gerson, Lowell W.] Summa Hlth Syst, Dept Emergency Med, Akron, OH USA. [Wenger, Neil S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Terrell, KM (reprint author), Indiana Univ, Sch Med, Dept Emergency Med, Indianapolis, IN USA. EM kterrel@iupui.edu RI Carpenter, Christopher/E-3720-2013 OI Carpenter, Christopher/0000-0002-2603-7157 FU AGS; John A. Hartford Foundation; Atlantic Philanthropies FX This project was funded by an award from the American Geriatrics Society (AGS) as part of the Geriatrics for Specialists Initiative, which is supported by the John A. Hartford Foundation. Drs. Terrell, Hustey, and Hwang are supported by Dennis W. Jahnigen Career Development Awards, which are funded by the AGS, the John A. Hartford Foundation, and Atlantic Philanthropies. This SAEM Geriatric Task Force Report was approved by the SAEM Board of Directors in September 2008. A related commentary appears on page 436. NR 82 TC 63 Z9 64 U1 1 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2009 VL 16 IS 5 BP 441 EP 449 DI 10.1111/j.1553-2712.2009.00382.x PG 9 WC Emergency Medicine SC Emergency Medicine GA 438IE UT WOS:000265548300012 PM 19344452 ER PT J AU Sonis, JH Triffleman, E King, L King, D AF Sonis, Jeffrey H. Triffleman, Elisa King, Lynda King, Daniel TI How to Write an NIH R13 Conference Grant Application SO ACADEMIC PSYCHIATRY LA English DT Article ID GUIDE AB Objective: The purpose of this article is to provide recommendations for writing a successful R13 conference grant proposal for the National Institutes of Health (NIH). Methods: The authors reviewed successful NIH conference grant proposal abstracts. They also reflect on their own experience in writing an NIH conference grant proposal and implementing a successful annual conference on research methods in the area of psychological trauma. Results: The key to a strong proposal is linkage among all of its sections, from the specific aims to the budget. The specific aims should be justified by the need for the conference and articulated in the background and significance section, and the aims, in turn, should drive the content and format of the conference. Conclusion: Conferences can be an important way to promote NIH scientific goals, by disseminating new findings, facilitating collaborations, and stimulating new lines of research. C1 [Sonis, Jeffrey H.] Univ N Carolina, Sch Med, Dept Social Med, Chapel Hill, NC 27599 USA. [Sonis, Jeffrey H.] Univ N Carolina, Dept Family Med, Chapel Hill, NC 27599 USA. [King, Lynda; King, Daniel] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [King, Lynda; King, Daniel] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [King, Lynda; King, Daniel] VA Boston Healthcare Syst, Boston, MA USA. RP Sonis, JH (reprint author), Univ N Carolina, Sch Med, Dept Social Med, CB7240,Wing D, Chapel Hill, NC 27599 USA. EM jsonis@med.unc.edu NR 13 TC 4 Z9 4 U1 1 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAY-JUN PY 2009 VL 33 IS 3 BP 256 EP 260 PG 5 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 467CI UT WOS:000267713700015 PM 19574528 ER PT J AU McCauley, J Ruggiero, KJ Resnick, HS Conoscenti, LM Kilpatrick, DG AF McCauley, Jenna Ruggiero, Kenneth J. Resnick, Heidi S. Conoscenti, Lauren M. Kilpatrick, Dean G. TI Forcible, drug-facilitated, and incapacitated rape in relation to substance use problems: Results from a national sample of college women SO ADDICTIVE BEHAVIORS LA English DT Article DE Drug-facilitated rape; Incapacitated; Forcible; College women; Binge drinking; Substance abuse ID ALCOHOL-CONSUMPTION; SEXUAL ASSAULT; VICTIMIZATION; TRAUMA; RISK; VULNERABILITY; EXPERIENCES; PERPETRATOR; ADOLESCENTS; OUTCOMES AB This is the first study to examine the relation between rape and substance use problems in college women as a function of three legally recognized forms of rape: forcible, incapacitated, and substance-facilitated rape. Data were collected via structured telephone interview with a large national sample of college women aged 18-34 years (n = 1980). Lifetime prevalence of any type of rape was 11.3% in the sample. Prevalence estimates for binge drinking and substance abuse were 15.8% and 19.8%, respectively. Lifetime experience of incapacitated rape and drug-alcohol facilitated rape, but not forcible rape, were associated with increased odds of past-year binge drinking and substance abuse. Findings have implications for secondary prevention and call for continued differentiation in assessment of rape type. (C) 2008 Elsevier Ltd. All rights reserved. C1 [McCauley, Jenna; Ruggiero, Kenneth J.; Resnick, Heidi S.; Kilpatrick, Dean G.] Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, Charleston, SC 29425 USA. [Conoscenti, Lauren M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. RP McCauley, J (reprint author), Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, POB 250852,165 Cannon St, Charleston, SC 29425 USA. EM mccaule@musc.edu FU National Institute of Justice (NIJ) [2005-WG-BX-0006] FX This research was supported by National Institute of Justice (NIJ) Grant #2005-WG-BX-0006 (PI: Dean G. Kilpatrick, Ph.D.). Views expressed in this article do not necessarily represent those of NU. NR 30 TC 34 Z9 34 U1 11 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD MAY PY 2009 VL 34 IS 5 BP 458 EP 462 DI 10.1016/j.addbeh.2008.12.004 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 425ZA UT WOS:000264675600009 PM 19162407 ER PT J AU Sakhuja, R Bhatt, DL AF Sakhuja, Rahul Bhatt, Deepak L. TI Getting real with drug-eluting stents: 5-year follow up of a real-world cohort SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID BARE-METAL STENTS; LARGE 2-INSTITUTIONAL COHORT; RANDOMIZED CLINICAL-TRIALS; CORONARY STENTS; MYOCARDIAL-INFARCTION; THROMBOSIS; OUTCOMES; METAANALYSIS; RESTENOSIS; IMPLANTATION C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sakhuja, Rahul] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM dlbhattmd@alum.mit.edu NR 26 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2009 VL 157 IS 5 BP 802 EP 804 DI 10.1016/j.ahj.2008.12.022 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 444NN UT WOS:000265987800009 PM 19376303 ER PT J AU Frisch, DR Giedrimas, E Mohanavelu, S Shui, A Ho, KKL Gibson, CM Josephson, ME Zimetbaum, PJ AF Frisch, Daniel R. Giedrimas, Evaldas Mohanavelu, Satishkumar Shui, Amy Ho, Kalon K. L. Gibson, C. Michael Josephson, Mark E. Zimetbaum, Peter J. TI Predicting Irreversible Left Ventricular Dysfunction After Acute Myocardial Infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CONGESTIVE-HEART-FAILURE; T-WAVE ALTERNANS; DEFIBRILLATOR IMPLANTATION; CARDIOVERTER-DEFIBRILLATOR; SURVIVAL; DISEASE; EVENTS; DEATH; RISK AB Patients with reduced left ventricular ejection fractions (LVEFs) and previous myocardial infarctions or heart failure are at increased mortality risk. Implantable cardioverter-defibrillators may mitigate this risk. The aim of this study was to identify patient characteristics at the time of presentation with ST elevation myocardial infarction (STEMI) that predict irreversible left ventricular dysfunction. From January 2003 to December 2005, patients presenting with STEMIs and an LVEFs after percutaneous coronary intervention <= 0.4 were included (n = 118). Clinical, angiographic, and electrocardiographic characteristics at the time of STEMI were evaluated to predict LVEF at >= 90 days. Multivariate analysis identified post-percutaneous coronary intervention LVEF <= 0.3 (odds ratio 5.4, 95% confidence interval 2.1 to 14.1, p = 0.001), presentation with Killip class >I (odds ratio 4.4, 95% confidence interval 1.5 to 12.6, p = 0.006), and Q waves on postrevascularization electrocardiography (odds ratio 6.3, 95% confidence interval 1.5 to 26.5, p = 0.011) to be significantly more common in the group with LVEFs <= 0.3 at >= 90 days. The presence of all 3 factors, present in 14 patients (12%), had a positive predictive value of 100% that LVEF would be <= 0.3 at >= 90 days. In conclusion, in patients with STEMIs referred for catheterization, a post-percutaneous coronary intervention LVEF <= 0.3, presentation with Killip class >I, and pathologic Q waves after revascularization each predicted that the LVEF measured at >= 90 days would remain <= 0.3. The presence of all 3 features had a positive predictive value of 100%. These findings may identify a high-risk group of patients who might benefit from early aggressive therapy such as an implantable cardioverter-defibrillator. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;103:1206-1209) C1 [Frisch, Daniel R.] Thomas Jefferson Univ, Div Cardiol, Philadelphia, PA 19107 USA. [Ho, Kalon K. L.; Gibson, C. Michael; Josephson, Mark E.; Zimetbaum, Peter J.] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. [Mohanavelu, Satishkumar; Shui, Amy] TIMI Study Grp, Boston, MA USA. RP Frisch, DR (reprint author), Thomas Jefferson Univ, Div Cardiol, Philadelphia, PA 19107 USA. EM daniel.frisch@jefferson.edu NR 13 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2009 VL 103 IS 9 BP 1206 EP 1209 DI 10.1016/j.amjcard.2009.01.028 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 442TK UT WOS:000265863300005 PM 19406260 ER PT J AU Simon, JA Chen, YH Bent, S AF Simon, Joel A. Chen, Yea-Hung Bent, Stephen TI The relation of alpha-linolenic acid to the risk of prostate cancer: a systematic review and meta-analysis SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT 5th International Congress on Vegetarian Nutrition CY MAR, 2008 CL Loma Linda Univ, Loma Linda, CA HO Loma Linda Univ ID POLYUNSATURATED FATTY-ACIDS; DIETARY-FAT; UNITED-STATES; FISH CONSUMPTION; PUBLICATION BIAS; ASSOCIATION; SERUM; CARCINOMA; ENERGY; COHORT AB Background: alpha-Linolenic acid (ALA; 18: 3n-3) has been associated inconsistently with an increased risk of prostate cancer. Additional studies have become available since the publication of 2 previous meta-analyses. Objective: The objective was to review the published data on the relation between ALA and prostate cancer. Design: We conducted a systematic review to identify studies that included data on ALA and risk of prostate cancer. Data were pooled from studies that compared the highest ALA quantile with the lowest ALA quantile, and risk estimates were combined by using a random-effects model. Results: The relation between ALA and prostate cancer is inconsistent across studies. We pooled data from 8 case-control and 8 prospective studies. The summary estimate revealed that high ALA dietary intakes or tissue concentrations are weakly associated with prostate cancer risk (relative risk [RR]: 1.20; 95% CI: 1.01, 1.43). When examined by study type (ie, retrospective compared with prospective or dietary ALA compared with tissue concentration) or by decade of publication, only the 6 studies examining blood or tissue ALA concentrations revealed a statistically significant association. With the exception of these studies, there was significant heterogeneity and evidence of publication bias. After adjustment for publication bias, there was no association between ALA and prostate cancer (RR: 0.96; 95% CI: 0.79, 1.17). Conclusions: Studies examining the relation between ALA and prostate cancer have produced inconsistent findings. High ALA intakes or high blood and adipose tissue concentrations of ALA may be associated with a small increased risk of prostate cancer. However, these conclusions are qualified because of the heterogeneity across studies and the likelihood of publication bias. Am J Clin Nutr 2009; 89(suppl): 1558S-64S. C1 [Simon, Joel A.; Bent, Stephen] Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. [Simon, Joel A.; Bent, Stephen] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA. [Chen, Yea-Hung] Univ Calif San Francisco, Sch Med, Osher Ctr Integrat Med, San Francisco, CA USA. RP Simon, JA (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, 4150 Clement St, San Francisco, CA 94121 USA. EM joel.simon@ucsf.edu NR 77 TC 60 Z9 62 U1 1 U2 7 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY 1 PY 2009 VL 89 IS 5 BP S1558 EP S1564 DI 10.3945/ajcn.2009.26736E PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 436EB UT WOS:000265394300044 PM 19321563 ER PT J AU Hachem, C Morgan, R Johnson, M Kuebeler, M El-Serag, H AF Hachem, Christine Morgan, Robert Johnson, Michael Kuebeler, Mark El-Serag, Hashem TI Statins and the Risk of Colorectal Carcinoma: A Nested Case-Control Study in Veterans With Diabetes SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID COENZYME-A REDUCTASE; CANCER-MORTALITY; UNITED-STATES; IN-VITRO; CHOLESTEROL; INHIBITORS; COLON; COHORT; DRUGS; APOPTOSIS AB OBJECTIVES: Experimental data indicate a possible preventive effect for statins in colorectal cancer (CRC). However, the available epidemiological data are conflicting. METHODS: We conducted a nested case-control study of veterans with diabetes in national databases of the Department of Veterans Affairs (VA) and Medicare-linked files. Cases were defined as incident CRC during January 2001-December 2002, sampled on incidence density. VA pharmacy benefits management (PBM) files were used to identify filled prescriptions for statins. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) after adjusting for potential confounding variables. Stratified analyses were conducted for potential effect modifiers. RESULTS: A total of 6,080 cases and 24,320 controls were examined. The mean age was 74 years, and the majority of patients were Caucasian (88%) and male (99%). Filled prescriptions of statins were recorded less frequently in cases (49%) than in controls (52%; OR: 0.88; 95% confidence interval (95% CI): 0.83-0.93). This inverse association remained significant after adjusting for inflammatory bowel disease, diabetes severity, cholecystectomy, liver disease, filled prescriptions for sulfonylurea, aspirin or NSAID use, or colorectal evaluation. Simvastatin comprised the majority (87%) of statin-filled prescriptions, and the association with risk of CRC with simvastatin was very similar to that of any statin. No significant associations were observed between the risk of CRC and nonstatin cholesterol (OR: 1.02; 95% CI 0.88-1.18) or triglyceride-lowering medications (OR: 0.96; 95% CI: 0.87-1.05). The significant inverse association was limited to Caucasians, patients without history of polyps, patients aged 65 years and older, and patients with colon cancer (excluding rectum). CONCLUSIONS: The use of statins was associated with a small reduction in the risk of colon cancer in patients with diabetes. However, the causal link is not clear. C1 [Hachem, Christine; Johnson, Michael; Kuebeler, Mark; El-Serag, Hashem] Dept Vet Affairs Med Ctr, Hlth Serv Res, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Hachem, Christine; El-Serag, Hashem] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Hachem, Christine] St Louis Univ, Dept Med, St Louis, MO 63103 USA. [Morgan, Robert] Univ Texas Houston, Sch Publ Hlth, Div Mangement Policy & Community Hlth, Houston, TX USA. [Johnson, Michael] Univ Houston, Dept Clin Sci & Adm, Coll Pharm, Houston, TX USA. RP El-Serag, H (reprint author), Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,Room 3A-320, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU Department of Veterans Affairs, Health Services Research and Development Service [HFP 90-020, IIR 02-081]; NIH [K24DK078154-03] FX This research was supported in part by the Department of Veterans Affairs, Health Services Research and Development Service, HFP 90-020 and IIR 02-081 (R. Morgan PI, M. Johnson Co-PI). EI-Serag is supported by NIH grant K24DK078154-03. NR 32 TC 39 Z9 39 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2009 VL 104 IS 5 BP 1241 EP 1248 DI 10.1038/ajg.2009.64 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 447VB UT WOS:000266219000022 PM 19352344 ER PT J AU Gellad, WF Detsky, AS Choudhry, NK AF Gellad, Walid F. Detsky, Allan S. Choudhry, Niteesh K. TI Implications of recent clinical trials on pay-for-performance SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material ID HEALTH-CARE; VASCULAR EVENTS; GLUCOSE CONTROL; QUALITY; RISK; OUTCOMES; TELMISARTAN; MANAGEMENT; RAMIPRIL; POINT C1 [Gellad, Walid F.] RAND Hlth, Pittsburgh, PA 15213 USA. [Gellad, Walid F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Detsky, Allan S.] Mt Sinai Hosp, Dept Med, Toronto, ON, Canada. [Detsky, Allan S.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Choudhry, Niteesh K.] Harvard Univ, Sch Med, Boston, MA USA. [Choudhry, Niteesh K.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. RP Gellad, WF (reprint author), RAND Hlth, 4570 5 Ave,Suite 600, Pittsburgh, PA 15213 USA. EM wgellad@rand.org NR 32 TC 5 Z9 6 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 1 PY 2009 VL 66 IS 9 BP 864 EP 867 DI 10.2146/ajhp080577 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 437RD UT WOS:000265503700019 PM 19386951 ER PT J AU Heckbert, SR Wiggins, KL Glazer, NL Dublin, S Psaty, BM Smith, NL Longstreth, WT Lumley, T AF Heckbert, Susan R. Wiggins, Kerri L. Glazer, Nicole L. Dublin, Sascha Psaty, Bruce M. Smith, Nicholas L. Longstreth, W. T., Jr. Lumley, Thomas TI Antihypertensive Treatment With ACE Inhibitors or beta-Blockers and Risk of Incident Atrial Fibrillation in a General Hypertensive Population SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID CONVERTING ENZYME-INHIBITORS; II RECEPTOR BLOCKADE; RANDOMIZED-TRIAL; PREVENTION; ONSET; METAANALYSIS; PREVALENCE; STROKE; MORBIDITY; MORTALITY AB BACKGROUND Secondary analyses of clinical trial data suggest that, compared with other agents, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are associated with lower risk of incident atrial fibrillation (AF) in patients with heart failure, but data from the hypertension trials have been inconsistent. Information is scant about the association of beta-blocker use with AF risk in hypertensive patients without heart failure. METHODS We conducted a population-based case-control study to determine whether anti hypertensive treatment with ACE inhibitors/ARBs or beta-blockers, compared with diuretics, was associated with the risk of incident AF in a community practice setting. All patients (810 AF cases, 1,512 control subjects) were members of Group Health (GH), an integrated health-care delivery system, were pharmacologically treated for hypertension, and did not have heart failure. Medical records were reviewed to confirm the diagnosis of incident AF and to collect information on medical conditions and health behaviors. Information on anti hypertensive medications was obtained from a pharmacy database. RESULTS Single-drug users of an ACE inhibitor/ARB had a lower risk of incident AF compared with single-drug users of a diuretic (adjusted odds ratio 0.63, 95% confidence interval 0.44-0.91). Single-drug use of beta-blockers was not significantly associated with lower AF risk (odds ratio 1.05, 95% confidence interval 0.73-1.52), and also none of the most commonly used two-drug regimens was significantly associated with AF risk, in comparison with single-drug use of diuretic. CONCLUSIONS In a general hypertensive population without heart failure, single-drug use of ACE inhibitors/ARBs was associated with lower AF risk. C1 [Heckbert, Susan R.; Wiggins, Kerri L.; Glazer, Nicole L.; Psaty, Bruce M.; Smith, Nicholas L.; Longstreth, W. T., Jr.; Lumley, Thomas] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Heckbert, Susan R.; Dublin, Sascha; Psaty, Bruce M.; Smith, Nicholas L.; Longstreth, W. T., Jr.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Heckbert, Susan R.; Dublin, Sascha; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [Wiggins, Kerri L.; Glazer, Nicole L.; Psaty, Bruce M.; Longstreth, W. T., Jr.] Univ Washington, Dept Med, Seattle, WA USA. [Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Heckbert, SR (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. EM heckbert@u.washington.edu RI CPRD, CPRD/B-9594-2017 FU National Heart, Lung and Blood Institute, Bethesda, MD [HL068986, HL043201, HL073410, HL068639]; National Institute on Aging [AG028954] FX This study was supported by grants HL068986, HL043201, HL073410, and HL068639 from the National Heart, Lung and Blood Institute, Bethesda, MD. S.D. was supported by grant AG028954 from the National Institute on Aging. NR 25 TC 32 Z9 34 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2009 VL 22 IS 5 BP 538 EP 544 DI 10.1038/ajh.2009.33 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 435HP UT WOS:000265335100017 PM 19265792 ER PT J AU Rogers, AM Shlipak, MG AF Rogers, Adam M. Shlipak, Michael G. TI C-Reactive Protein, Statins, and Cardiovascular Risk: What Can JUPITER Teach Us? SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID CORONARY-HEART-DISEASE; CHOLESTEROL LEVELS; RANDOMIZED-TRIAL; MEN; PRAVASTATIN; PREVENTION; EVENTS; WOMEN; INFLAMMATION; THERAPY C1 [Rogers, Adam M.; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Shlipak, MG (reprint author), VA Med Ctr 111A1, Gen Internal Med Sect, 4150 Clement St, San Francisco, CA 94121 USA. EM michael.shlipak@ucsj.edu NR 11 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2009 VL 53 IS 5 BP 737 EP 740 DI 10.1053/j.ajkd.2009.03.003 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 443PY UT WOS:000265923500005 PM 19393472 ER PT J AU Rosen, CJ Klibanski, A AF Rosen, Clifford J. Klibanski, Anne TI Bone, Fat, and Body Composition: Evolving Concepts in the Pathogenesis of Osteoporosis SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE Adipokines; Anorexia nervosa; Bone marrow stromal cells; Hypothalamus; Sympathetic nervous system ID ANOREXIA-NERVOSA; ADOLESCENT GIRLS; MINERAL DENSITY; SECRETORY DYNAMICS; BULIMIA-NERVOSA; PEPTIDE-YY; OSTEOBLAST DIFFERENTIATION; MECHANICAL SIGNALS; MOLECULAR CLOCK; HIGH-FREQUENCY AB Disorders of body composition, including obesity and osteoporosis, have reached record proportions. Coincidentally, our understanding of the mechanisms controlling body mass also has greatly improved. Shared regulation at the hypothalamus and the bone marrow highlight major bone-fat interactions. The hypothalamus modulates fat and bone via the sympathetic nervous system by regulating appetite, insulin sensitivity, energy use, and skeletal remodeling. In the bone marrow, fat and bone cells arise from the same stem cells. Insights from disorders such as anorexia nervosa provide a new rationale for examining the mechanisms that link bone to fat. This article explores these relationships in the context of a new paradigm with implications for obesity and osteoporosis. (C) 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 409-414 C1 Maine Med Ctr, Res Inst, Portland, ME 04102 USA. Massachusetts Gen Hosp, Portland, ME USA. Harvard Univ, Sch Med, Portland, ME USA. Maine Med Ctr, Inst Res, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rosen, CJ (reprint author), Maine Med Ctr, Res Inst, 81 Res Dr, Scarborough, ME 04074 USA. EM rosenc@mmc.org FU National Institutes of Health [AR45433, 54604] FX National Institutes of Health grants AR45433 and 54604. NR 55 TC 103 Z9 106 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2009 VL 122 IS 5 BP 409 EP 414 DI 10.1016/j.amjmed.2008.11.027 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 433XB UT WOS:000265238000003 PM 19375545 ER PT J AU Slatore, CG Bryson, CL Au, DH AF Slatore, Christopher G. Bryson, Chris L. Au, David H. TI The Association of Inhaled Corticosteroid Use with Serum Glucose Concentration in a Large Cohort SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; DIABETES-MELLITUS; LUNG HEALTH; VENTILATORY CAPACITY; RISK; FRACTURE; COPD; TRIAMCINOLONE; ASTHMA; ADULTS AB BACKGROUND: Inhaled corticosteroids (ICSs) are widely used in the treatment of obstructive lung disease. ICSs have been shown to be systemically absorbed. The association between ICS and serum glucose concentration is unknown. METHODS: To explore the association of ICS dosing with serum glucose concentration, we used a prospective cohort study of US veterans enrolled in 7 primary care clinics between December 1996 and May 2001 with 1 or more glucose measurements while at least 80% adherent to ICS dosing. The association between ICS dose from pharmacy records standardized to daily triamcinolone equivalents and serum glucose concentration was examined with generalized estimating equations controlling for confounders, including systemic corticosteroid use. RESULTS: Of the 1698 subjects who met inclusion criteria, 19% had self-reported diabetes. The mean daily dose of ICS in triamcinolone equivalents was 621 mu g (standard deviation 555) and 610 mu g (standard deviation 553) for subjects with and without diabetes, respectively. After controlling for systemic corticosteroid use and other potential confounders, no association between ICS and serum glucose was found for subjects without diabetes. However, among subjects with self-reported diabetes, every additional 100 mu g of ICS dose was associated with an increased glucose concentration of 1.82 mg/dL (P value .007; 95% confidence interval [CI], 0.49-3.15). Subjects prescribed antiglycemic medications had an increase in serum glucose of 2.65 mg/dL (P value .003; 95% CI, 0.88-4.43) for every additional 100 mu g ICS dose. CONCLUSION: Among diabetic patients, ICS use is associated with an increased serum glucose concentration in a dose-response manner. (C) 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 472-478 C1 [Slatore, Christopher G.; Bryson, Chris L.; Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Slatore, Christopher G.; Bryson, Chris L.; Au, David H.] Univ Washington, Dept Med, Seattle, WA USA. RP Slatore, CG (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM cslatore@u.washington.edu OI Slatore, Christopher/0000-0003-0958-8122 NR 43 TC 30 Z9 32 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2009 VL 122 IS 5 BP 472 EP 478 DI 10.1016/j.amjmed.2008.09.048 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 433XB UT WOS:000265238000015 PM 19375557 ER PT J AU Nogueira, RG Yoo, AJ Buonanno, FS Hirsch, JA AF Nogueira, R. G. Yoo, A. J. Buonanno, F. S. Hirsch, J. A. TI Endovascular Approaches to Acute Stroke, Part 2: A Comprehensive Review of Studies and Trials SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Review ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN-ACTIVATOR; INTRAARTERIAL THROMBOLYTIC THERAPY; RETINAL ARTERY-OCCLUSION; RANDOMIZED CONTROLLED-TRIAL; MECHANICAL EMBOLUS REMOVAL; SEX-BASED DIFFERENCES; INTERVENTIONAL MANAGEMENT; PROACT-II; INTRAVENOUS THROMBOLYSIS AB Reperfusion remains the mainstay of acute ischemic stroke treatment. Endovascular therapy has become a promising alternative for patients who are ineligible for or have failed intravenous (IV) thrombolysis, The conviction that recanalization of properly selected patients is essential for the achievement of good clinical outcomes has led to the rapid and widespread growth in the adoption of endovascular stroke therapies. However, comparisons of the recent reperfusion studies have brought into question the strength of the association between revascularization and improved clinical outcome. Despite higher rates of recanalization, the mechanical thrombectomy studies have demonstrated substantially lower rates of good outcomes compared with IV and/or intra-arterial thrombolytic trials. However, such analyses disregard important differences in clot location and burden, baseline stroke severity, time from stroke onset to treatment, and patient selection in these studies. Many clinical trials are testing novel devices and drugs as well as the paradigm of physiology-based stroke imaging as a treatment-selection tool. The objective of this article is to provide a comprehensive review of the relevant past, current, and upcoming data on endovascular stroke therapy with a special focus on the prospective studies and randomized clinical trials. C1 [Nogueira, R. G.; Yoo, A. J.; Hirsch, J. A.] Harvard Univ, Massachusetts Gen Hosp, Endovasc Neurosurg Intervent Neuroradiol Sect, Dept Neurol,Med Sch, Boston, MA USA. [Nogueira, R. G.; Buonanno, F. S.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Dept Neurol,Med Sch, Boston, MA USA. [Nogueira, R. G.; Buonanno, F. S.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Dept Neurol,Med Sch, Boston, MA USA. [Nogueira, R. G.; Buonanno, F. S.] Harvard Univ, Massachusetts Gen Hosp, Neurocrit Care & Vasc Neurol Sect, Dept Neurol,Med Sch, Boston, MA USA. RP Nogueira, RG (reprint author), Massachusetts Gen Hosp, Dept Intervent Neuroradiol & Endovasc Neurosurg, 55 Fruit St,GRB-2-241, Boston, MA 02114 USA. EM rnogueira@partners.org NR 86 TC 67 Z9 69 U1 0 U2 6 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 2009 VL 30 IS 5 BP 859 EP 875 DI 10.3174/ajnr.A1604 PG 17 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 446PG UT WOS:000266133000002 PM 19386727 ER PT J AU Konstas, AA Goldmakher, GV Lee, TY Lev, MH AF Konstas, A. A. Goldmakher, G. V. Lee, T. -Y. Lev, M. H. TI Theoretic Basis and Technical Implementations of CT Perfusion in Acute Ischemic Stroke, Part 2: Technical Implementations SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Review ID CEREBRAL-BLOOD-FLOW; ARTERIAL INPUT FUNCTION; SINGULAR-VALUE DECOMPOSITION; MULTIDETECTOR COMPUTED-TOMOGRAPHY; WEIGHTED MRI; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; QUANTITATIVE ASSESSMENT; DECONVOLUTION ANALYSIS; INFARCT SIZE; PENUMBRA AB CT perfusion (CTP) is a functional imaging technique that provides important information about capillary-level hemodynamics of the brain parenchyma and is a natural complement to the strengths of unenhanced CT and CT angiography in the evaluation of acute stroke, vasospasm, and other neurovascular disorders. CTP is critical in determining the extent of irreversibly infarcted brain tissue (infarct "core") and the severely ischemic but potentially salvageable tissue ("penumbra"). This is achieved by generating parametric maps of cerebral blood flow, cerebral blood volume, and mean transit time. C1 [Konstas, A. A.; Goldmakher, G. V.; Lev, M. H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lee, T. -Y.] Robarts Res Inst, Imaging Res Labs, London, ON N6A 5C1, Canada. RP Konstas, AA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM akonstas@partners.org RI Lee, Ting-Yim/M-1721-2013 NR 66 TC 82 Z9 89 U1 0 U2 7 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 2009 VL 30 IS 5 BP 885 EP 892 DI 10.3174/ajnr.A1492 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 446PG UT WOS:000266133000004 PM 19299489 ER PT J AU Stefancyk, AL AF Stefancyk, Amanda L. TI Placing the Patient at the Center of Care SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 [Stefancyk, Amanda L.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. RP Stefancyk, AL (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. EM astefancyk@partners.org NR 1 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD MAY PY 2009 VL 109 IS 5 BP 27 EP 28 PG 2 WC Nursing SC Nursing GA 441XL UT WOS:000265803700014 PM 19411898 ER PT J AU Markland, AD Richter, HE Burgio, KL Bragg, C Hernandez, AL Subak, LL AF Markland, Alayne D. Richter, Holly E. Burgio, Kathryn L. Bragg, Charlotte Hernandez, Alexandra L. Subak, Leslee L. TI Fecal incontinence in obese women with urinary incontinence: prevalence and role of dietary fiber intake SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Urogynecologic-Society CY SEP 04-06, 2008 CL Chicago, IL SP Amer Urogynecol Soc DE diet; fecal incontinence; female; food frequency questionnaire; obesity; stress incontinence; urge incontinence; urinary incontinence; weight loss ID FOOD-FREQUENCY QUESTIONNAIRE; PELVIC FLOOR DISORDERS; WEIGHT-LOSS SURGERY; QUALITY-OF-LIFE; ANAL INCONTINENCE; SEVERITY INDEX; UNITED-STATES; US WOMEN; COMMUNITY; HEALTH AB OBJECTIVE: This study estimates the prevalence of fecal incontinence (FI) in overweight and obese women with urinary incontinence and compares dietary intake in women with and without FI. STUDY DESIGN: A total of 36 incontinent and overweight women in the Program to Reduce Incontinence by Diet and Exercise clinical trial were included. FI was defined as monthly or greater loss of mucus, liquid, or solid stool. Dietary intake was quantified using the Block Food Frequency Questionnaire. RESULTS: Women had a mean (+/- SD) age of 53 +/- 10 years, body mass index of 36 +/- 6 kg/m(2), and 19% were African American. Prevalence of FI was 16% (n = 55). In multivariable analyses, FI was independently associated with low fiber intake, higher depressive symptoms, and increased urinary tract symptoms (all P < .05). CONCLUSION: Overweight and obese women report a high prevalence of monthly FI associated with low dietary fiber intake. Increasing dietary fiber may be a treatment for FI. C1 [Markland, Alayne D.] Univ Alabama, Div Gerontol Geriatr & Palliat Care, Dept Med, Birmingham Vet Affairs Med Ctr,Sch Med, Birmingham, AL 35233 USA. [Markland, Alayne D.; Burgio, Kathryn L.] Birmingham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Birmingham, AL USA. [Richter, Holly E.] Univ Alabama, Sch Med, Div Womens Pelv Med & Reconstruct Surg, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. [Bragg, Charlotte] Univ Alabama, Sch Med, Dept Prevent Med, Birmingham, AL 35233 USA. [Subak, Leslee L.] Univ Calif San Francisco, Sch Med, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Hernandez, Alexandra L.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. [Subak, Leslee L.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Subak, Leslee L.] Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. RP Markland, AD (reprint author), Univ Alabama, Div Gerontol Geriatr & Palliat Care, Dept Med, Birmingham Vet Affairs Med Ctr,Sch Med, GRECC 11-G,Room 8220,700 S 19 St, Birmingham, AL 35233 USA. EM amarkland@aging.uab.edu FU NIDDK NIH HHS [U01 DK067862, K24 DK080775, U01 DK067861, U01 DK067860-05S1, U01 DK067860] NR 37 TC 1 Z9 1 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2009 VL 200 IS 5 AR 566.e1 DI 10.1016/j.ajog.2008.11.019 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 434CW UT WOS:000265253800038 PM 19136088 ER PT J AU Takeshita, D Gale, JT Montgomery, EB Bahar, S Moss, F AF Takeshita, Daisuke Gale, John T. Montgomery, Erwin B., Jr. Bahar, Sonya Moss, Frank TI Analyzing spike trains with circular statistics SO AMERICAN JOURNAL OF PHYSICS LA English DT Article DE bioelectric phenomena; neurophysiology; physics education; statistics; stochastic processes; time series ID STIMULUS-LOCKED RESPONSES; CAUDAL PHOTORECEPTOR; SIGNAL-TRANSDUCTION; SYNCHRONIZATION; OSCILLATORS; PADDLEFISH; NOISE; CELLS; ELECTRORECEPTORS; TRANSMISSION AB In neuroscience, specifically electrophysiology, it is common to replace a measured sequence of action potentials or spike trains with delta functions prior to analysis. We apply a method called circular statistics to a time series of delta functions and show that the method is equivalent to the power spectrum. This technique allows us to easily visualize the idea of the power spectrum of spike trains and easily reveals oscillatory and stochastic behavior. We provide several illustrations of the method and an example suitable for students, and suggest that the method might be useful for courses in introductory biophysics and neuroscience. C1 [Takeshita, Daisuke; Bahar, Sonya; Moss, Frank] Univ Missouri, Dept Phys & Astron, Ctr Neurodynam, St Louis, MO 63121 USA. [Gale, John T.] Harvard Univ, Dept Neurosurg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Montgomery, Erwin B., Jr.] Univ Wisconsin, Dept Neurol, Natl Primate Res Ctr, Dept Biomed Engn, Madison, WI 53792 USA. [Montgomery, Erwin B., Jr.] Univ Wisconsin, Dept Communicat Disorders, Madison, WI 53792 USA. RP Takeshita, D (reprint author), Univ Missouri, Dept Phys & Astron, Ctr Neurodynam, St Louis, MO 63121 USA. RI Takeshita, Daisuke/I-2592-2016 OI Takeshita, Daisuke/0000-0002-2599-0827 NR 30 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC PHYSICS TEACHERS AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0002-9505 J9 AM J PHYS JI Am. J. Phys. PD MAY PY 2009 VL 77 IS 5 BP 424 EP 429 DI 10.1119/1.3090827 PG 6 WC Education, Scientific Disciplines; Physics, Multidisciplinary SC Education & Educational Research; Physics GA 433IK UT WOS:000265197300006 ER PT J AU Gourcerol, G Wang, L Adelson, DW Larauche, M Tache, Y Million, M AF Gourcerol, G. Wang, L. Adelson, D. W. Larauche, M. Tache, Y. Million, M. TI Cholinergic giant migrating contractions in conscious mouse colon assessed by using a novel noninvasive solid-state manometry method: modulation by stressors SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE colon; mice; giant migrating contractions; manometry; stress; corticotropin releasing factor-overexpressing ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; WATER-AVOIDANCE STRESS; MOTOR-ACTIVITY; MYENTERIC NEURONS; NITRIC-OXIDE; MYOELECTRICAL ACTIVITY; NITRERGIC REGULATION; POSTOPERATIVE ILEUS; RECEPTOR SUBTYPE-1 AB Gourcerol G, Wang L, Adelson DW, Larauche M, Tache Y, Million M. Cholinergic giant migrating contractions in conscious mouse colon assessed by using a novel noninvasive solid-state manometry method: modulation by stressors. Am J Physiol Gastrointest Liver Physiol 296: G992-G1002, 2009. First published March 19, 2009; doi:10.1152/ajpgi.90436.2008.-There is a glaring lack of knowledge on mouse colonic motility in vivo, primarily due to unavailability of adequate recording methods. Using a noninvasive miniature catheter pressure transducer inserted into the distal colon, we assessed changes in colonic motility in conscious mice induced by various acute or chronic stressors and determined the neurotransmitters mediating these changes. Mice exposed to restraint stress (RS) for 60 min displayed distal colonic phasic contractions including high-amplitude giant migrating contractions (GMCs), which had peak amplitudes >25 mmHg and occurred at a rate of 15-25 h (1) of which over 50% were aborally propagative. Responses during the first 20-min of RS were characterized by high-frequency and high-amplitude contractions that were correlated with defecation. RS-induced GMCs and fecal pellet output were blocked by atropine (0.5 mg/kg ip) or the corticotrophin releasing factor (CRF) receptor antagonist astressin-B (100 mu g/kg ip). RS activated colonic myenteric neurons as shown by Fos immunoreactivity. In mice previously exposed to repeated RS (60 min/day, 14 days), or in transgenic mice that overexpress CRF, the duration of stimulation of phasic colonic contractions was significantly shorter (10 vs. 20 min). In contrast to RS, abdominal surgery abolished colonic contractions including GMCs. These findings provide the first evidence for the presence of frequent cholinergic-dependent GMCs in the distal colon of conscious mice and their modulation by acute and chronic stressors. Noninvasive colonic manometry opens new venues to investigate colonic motor function in genetically modified mice relevant to diseases that involve colonic motility alterations. C1 [Million, M.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, Dept Med,Div Digest Dis, Los Angeles, CA 90073 USA. RP Million, M (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, CURE Bldg 115,Rm 118B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmulaget@ucla.edu OI Larauche, Muriel/0000-0003-3320-3675; Adelson, David/0000-0002-4623-6030 FU National Institute of Diabetes and Digestive and Kidney Diseases [R21 DK-068155, RO1 DK078676, DK-57238]; Veterans Affairs Career Scientist Award; Veterans Affairs Merit Award; French Foreign Office; French Society of Gastroenterology FX This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants R21 DK-068155 and RO1 DK078676 (M. Million), DK-57238; Veterans Affairs Career Scientist Award and Veterans Affairs Merit Award (Y. Tache), the French Foreign Office (Egide program) and the French Society of Gastroenterology (S.N.F.G.E.) (G. Gourcerol). NR 63 TC 16 Z9 16 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 2009 VL 296 IS 5 BP G992 EP G1002 DI 10.1152/ajpgi.90436.2008 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 451EG UT WOS:000266452900003 PM 19299579 ER PT J AU Goldman, RK Azar, AS Mulvaney, JM Hinojosa-Laborde, C Haywood, JR Brooks, VL AF Goldman, Robert K. Azar, Afaf S. Mulvaney, Julia M. Hinojosa-Laborde, Carmen Haywood, Joseph R. Brooks, Virginia L. TI Baroreflex sensitivity varies during the rat estrous cycle: role of gonadal steroids SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE renal sympathetic nerve activity; ovariectomy; diurnal; telemetry ID HORMONE REPLACEMENT THERAPY; AMBULATORY BLOOD-PRESSURE; NITRIC-OXIDE SYNTHASE; POSTMENOPAUSAL WOMEN; HEART-RATE; OVARIECTOMIZED RATS; MENSTRUAL-CYCLE; FEMALE RATS; AUTONOMIC FUNCTION; GENDER-DIFFERENCES AB Goldman RK, Azar AS, Mulvaney JM, Hinojosa-Laborde C, Haywood JR, Brooks VL. Baroreflex sensitivity varies during the rat estrous cycle: role of gonadal steroids. Am J Physiol Regul Integr Comp Physiol 296: R1419-R1426, 2009. First published March 4, 2009; doi:10.1152/ajpregu.91030.2008.- Baroreflex sensitivity (BRS) increases in women during the luteal phase of the menstrual cycle, when gonadal hormones are elevated, but whether a similar cycle-dependent variation in BRS occurs in rats is unknown. In addition, whether cyclic BRS changes depend on gonadal steroids has not been previously investigated. To test these hypotheses, BRS was determined in cycling female rats using two approaches: 1) baroreflex control of renal sympathetic nerve activity (RSNA) in anesthetized rats; 2) cardiovagal spontaneous BRS (sBRS) in conscious rats instrumented for continuous telemetric measurements of mean arterial pressure ( MAP) and heart rate (HR). MAP, HR, and sBRS were also measured in rats 2-3 and 5-6 wk following ovariectomy (OVX), to eliminate gonadal steroids. In anesthetized rats, RSNA BRS gain was increased ( P < 0.01) during proestrus (-4.8 +/- 0.5% control/mmHg) compared with diestrus/estrus (-2.8 +/- 0.3% control/mmHg). Similarly, a proestrous peak in sBRS was observed in conscious rats (1.66 +/- 0.07 ms/mmHg, proestrus; 1.48 +/- 0.06 ms/mmHg, diestrus/estrus; P < 0.001). OVX eliminated estrous cycle-induced variation in sBRS. In addition, OVX reduced (P < 0.05) diurnal variations in MAP (5.9 +/- 0.3 vs. 3.9 +/- 0.5 mmHg) and HR [54 +/- 4 vs. 39 +/- 3 beats per minute (bpm)], and abolished diurnal variations in sBRS. Finally, while MAP, HR, and sBRS were decreased 2 - 3 wk following OVX, similar to 3 wk later, MAP and sBRS increased, and HR decreased further. No changes in MAP, HR, or sBRS were seen with time in sham OVX controls. In summary, RSNA and cardiovagal sBRS vary during the rat estrous cycle, and this variation is abolished by OVX. We conclude that sex steroid hormones are required for both cyclic and diurnal changes in BRS in rats. C1 [Azar, Afaf S.; Mulvaney, Julia M.; Brooks, Virginia L.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Goldman, Robert K.] Portland VA Med Ctr, Dept Surg, Portland, OR USA. [Hinojosa-Laborde, Carmen] Univ Texas Hlth Sci Ctr San Antonio, Dept Anesthesiol, San Antonio, TX 78229 USA. [Haywood, Joseph R.] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA. RP Brooks, VL (reprint author), Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. EM brooksv@ohsu.edu FU National Institutes of Health [HL-088552, HL-03153]; Medical Research Foundation; Collins Foundation; American Heart Association FX This work was supported, in part, by funding from the Medical Research Foundation ( to R. K. Goldman and V. L. Brooks), the Collins Foundation ( to R. K. Goldman), the American Heart Association ( to V. L. Brooks), and National Institutes of Health Grants HL-088552 ( to V. L. Brooks) and HL-03153 ( to C. Hinajosa-Laborde). NR 58 TC 27 Z9 27 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAY PY 2009 VL 296 IS 5 BP R1419 EP R1426 DI 10.1152/ajpregu.91030.2008 PG 8 WC Physiology SC Physiology GA 448EW UT WOS:000266246900016 PM 19261912 ER PT J AU Goodman, M Hazlett, EA New, AS Koenigsberg, HW Siever, L AF Goodman, Marianne Hazlett, Erin A. New, Antonia S. Koenigsberg, Harold W. Siever, Larry TI Quieting the Affective Storm of Borderline Personality Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID AFFECTIVE INSTABILITY; IMPULSIVITY; STARTLE C1 [Goodman, Marianne] James J Peters VA Med Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY USA. RP Goodman, M (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Marianne.goodman@va.gov FU NIMH NIH HHS [MH-067918, MH-073911] NR 14 TC 6 Z9 6 U1 1 U2 3 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 MAY PY 2009 VL 166 IS 5 BP 522 EP 528 DI 10.1176/appi.ajp.2009.08121836 PG 7 WC Psychiatry SC Psychiatry GA 439YA UT WOS:000265662500006 PM 19411378 ER PT J AU Zheng, L Mack, WJ Dagerman, KS Hsiao, JK Lebowitz, BD Lyketsos, CG Stroup, TS Sultzer, DL Tariot, PN Vigen, C Schneider, LS AF Zheng, Ling Mack, Wendy J. Dagerman, Karen S. Hsiao, John K. Lebowitz, Barry D. Lyketsos, Constantine G. Stroup, T. Scott Sultzer, David L. Tariot, Pierre N. Vigen, Cheryl Schneider, Lon S. TI Metabolic Changes Associated With Second-Generation Antipsychotic Use in Alzheimer's Disease Patients: The CATIE-AD Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT International Conference on Alzheimers Disease CY JUL 26-31, 2008 CL Chicago, IL ID PLACEBO-CONTROLLED TRIALS; DOUBLE-BLIND; BEHAVIORAL DISTURBANCES; CARDIOVASCULAR-DISEASE; CLINICAL-TRIAL; DEMENTIA; PSYCHOSIS; RISPERIDONE; OLANZAPINE; SCHIZOPHRENIA AB Objective: The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer's disease are frequently treated with these antipsychotics, but limited data are available on their metabolic effects. Method: The authors assessed 186 male and 235 female Alzheimer's disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotic use (i.e., olanzapine, quetiapine, and risperidone) throughout the 36-week trial, using logistic regression and mixed-effects models. Results: Women showed significant weight gain (0.14 lb/week of use) while change was nonsignificant in men. Clinically significant weight gain (i.e., >= 7% of body weight) was seen among patients with antipsychotic use <= 12 weeks (odds ratio [OR]=1.56, 95% CI=0.53 to 4.58), between 12 and 24 weeks (OR=2.89, 95% CI=0.97 to 8.64), and >24 weeks (OR= 3.38, 95% CI=1.24 to 9.23) relative to patients who did not use antipsychotics during the trial. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 lb/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (-0.19 mg/dl/week) and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides. Conclusion: Second-generation antipsychotic use was associated with weight gain in women, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimer's disease treated with second-generation antipsychotics should be monitored closely. C1 Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ Calif San Diego, Sch Med, Div Geriatr Psychiat, La Jolla, CA 92093 USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Johns Hopkins Bayview Med Ctr, Dept Psychiat, Baltimore, MD USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. VA Greater Angeles Healthcare Syst, Gero Neuropsychiat Div, Los Angeles, CA USA. Banner Alzheimers Inst, Phoenix, AZ USA. RP Schneider, LS (reprint author), 1510 San Pablo St, Los Angeles, CA 90033 USA. EM lschneid@usc.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 FU NIMH NIH HHS [N01 MH-9001, N01 MH90001] NR 29 TC 36 Z9 38 U1 1 U2 7 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 MAY PY 2009 VL 166 IS 5 BP 583 EP 590 DI 10.1176/appi.ajp.2008.08081218 PG 8 WC Psychiatry SC Psychiatry GA 439YA UT WOS:000265662500013 PM 19369318 ER PT J AU Wisniewski, SR Rush, AJ Nierenberg, AA Gaynes, BN Warden, D Luther, JF McGrath, PJ Lavori, PW Thase, ME Fava, M Trivedi, MH AF Wisniewski, Stephen R. Rush, A. John Nierenberg, Andrew A. Gaynes, Bradley N. Warden, Diane Luther, James F. McGrath, Patrick J. Lavori, Philip W. Thase, Michael E. Fava, Maurizio Trivedi, Madhukar H. TI Can Phase III Trial Results of Antidepressant Medications Be Generalized to Clinical Practice? A STAR*D Report SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; MAJOR DEPRESSIVE DISORDER; DIAGNOSTIC SCREENING QUESTIONNAIRE; RANDOMIZED CONTROLLED-TRIALS; MEASUREMENT-BASED CARE; ILLNESS RATING-SCALE; REPORT QIDS-SR; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; EXTERNAL VALIDITY AB Objective: Phase III clinical trials for depression enroll participants with major depressive disorder according to stringent inclusion and exclusion criteria. These patients may not be representative of typical depressed patients seeking treatment. This analysis used data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project-which used broad inclusion and minimal exclusion criteria-to evaluate whether phase III clinical trials recruit representative depressed outpatients. Method: Of 2,855 participants, 22.2% met typical entry criteria for phase III clinical trials (efficacy sample) and 77.8% did not (nonefficacy sample). These groups were compared regarding baseline socio-demographic and clinical features and the characteristics and outcomes of acute-phase treatment. Results: The efficacy sample had a shorter average duration of illness and lower rates of family history of substance abuse, prior suicide attempts, and anxious and atypical symptom features. Despite similar medication dosing and time at exit dose, the efficacy participants tolerated citalopram better. They also had higher rates of response (51.6% versus 39.1%) and remission (34.4% versus 24.7%). These differences persisted even after adjustments for baseline differences. Conclusions: Phase III trials do not recruit representative treatment-seeking depressed patients. Broader phase III inclusion criteria would increase the generalizability of results to practice, potentially reducing placebo response and remission rates (reducing the risk of failed trials) but at the risk of some increase in adverse events. C1 [Wisniewski, Stephen R.] Univ Pittsburgh, Epidemiol Data Ctr, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Texas SW Med Ctr Dallas, Dept Clin Sci & Psychiat, Dallas, TX 75390 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. New York State Psychiat Inst & Hosp, Depress Evaluat Serv, New York, NY 10032 USA. Columbia Univ, New York, NY USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP Wisniewski, SR (reprint author), Univ Pittsburgh, Epidemiol Data Ctr, Grad Sch Publ Hlth, 127 Parran Hall,130 De Soto St, Pittsburgh, PA 15261 USA. EM wisniew@edc.pitt.edu RI McGrath, Patrick/I-6410-2013; OI Rush, Augustus/0000-0003-2004-2382; McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030 FU NIMH NIH HHS [N01 MH-90003] NR 29 TC 117 Z9 120 U1 0 U2 0 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 MAY PY 2009 VL 166 IS 5 BP 599 EP 607 DI 10.1176/appi.ajp.2008.08071027 PG 9 WC Psychiatry SC Psychiatry GA 439YA UT WOS:000265662500015 PM 19339358 ER PT J AU Copeland, LA Miller, AL Welsh, DE McCarthy, JF Zeber, JE Kilbourne, AM AF Copeland, Laurel A. Miller, Alexander L. Welsh, Deborah E. McCarthy, John F. Zeber, John E. Kilbourne, Amy M. TI Clinical and Demographic Factors Associated With Homelessness and Incarceration Among VA Patients With Bipolar Disorder SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SERIOUS MENTAL-ILLNESS; JAIL DIVERSION; THERAPEUTIC ALLIANCE; MEDICATION ADHERENCE; TREATMENT RETENTION; HEALTH-SERVICES; SUBSTANCE-ABUSE; VETERANS; POPULATION; CLIENTS AB Objectives. We assessed the association between homelessness and incarceration in Veterans Affairs patients with bipolar disorder. Methods. We used logistic regression to model each participant's risk of incarceration or homelessness after we controlled for known risk factors. Results. Of 435 participants, 12% reported recent homelessness (within the past month), and 55% reported lifetime homelessness. Recent and lifetime incarceration rates were 2% and 55%, respectively. In multivariate models, current medication adherence (based on a 5-point scale) was independently associated with a lower risk of lifetime homelessness (odds ratio [OR]=0.80 per point, range 0-4; 95% confidence interval [CI]=0.66, 0.96), and lifetime incarceration increased the risk of lifetime homelessness (OR=4.4; 95% CI=2.8, 6.9). Recent homelessness was associated with recent incarceration (OR=26.4; 95% CI=5.2, 133.4). Lifetime incarceration was associated with current substance use (OR=2.6; 95% CI=2.7, 6.7) after control for lifetime homelessness (OR=4.2; 95% CI=2.7, 6.7). Conclusions. Recent and lifetime incarceration and homelessness were strongly associated with each other. Potentially avoidable or treatable correlates included current medication nonadherence and substance use. Programs that better coordinate psychiatric and drug treatment with housing programs may reduce the cycle of incarceration, homelessness, and treatment disruption within this vulnerable patient population. (Am J Public Health. 2009;99:871-877. doi:10. 2105/AJ PH.2008.149989) C1 [Copeland, Laurel A.; Miller, Alexander L.; Zeber, John E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Welsh, Deborah E.; McCarthy, John F.; Kilbourne, Amy M.] Dept Vet Affairs, Ann Arbor, MI USA. [Kilbourne, Amy M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Copeland, LA (reprint author), S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd Verdict 11C6, San Antonio, TX 78229 USA. EM copelandl@uthscsa.edu OI Copeland, Laurel/0000-0002-9478-0209 FU Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development (VA HSRD) [VA HSRD IIR 02-283, VA HSRD IIR-05-326]; Merit Review Entry Program [MRP-05-145] FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (VA HSRD) Service (grant VA HSRD IIR 02-283; principal investigator: A.M. Mlbourne) and the VERDICT Research Program at the South Texas Veterans Health Care System, San Antonio; the University of Texas Health Science Center at San Antonio; and the Serious Mental Illness Treatment Research & Evaluation Center, VA Ann Arbor Healthcare System, Ann Arbor, MI. L.A. Copeland is funded by the Merit Review Entry Program (grant MRP-05-145; from the VA HSRD Service). A. L. Miller and J. E. Zeber are partially supported by the VA HSRD Service (grant VA HSRD IIR-05-326; principal investigator: L.A. Copeland). NR 46 TC 17 Z9 17 U1 1 U2 9 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2009 VL 99 IS 5 BP 871 EP 877 DI 10.2105/AJPH.2008.149989 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 441ZI UT WOS:000265808800021 PM 19299667 ER PT J AU Pandharipande, PV Choy, G del Carmen, MG Gazelle, GS Russell, AH Lee, SI AF Pandharipande, Pari V. Choy, Garry del Carmen, Marcela G. Gazelle, G. Scott Russell, Anthony H. Lee, Susanna I. TI MRI and PET/CT for Triaging Stage 1B Clinically Operable Cervical Cancer to Appropriate Therapy: Decision Analysis to Assess Patient Outcomes (vol 192, pg 802, 2009) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Correction C1 [Pandharipande, Pari V.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Russell, Anthony H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [del Carmen, Marcela G.] Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA. [Pandharipande, Pari V.; Lee, Susanna I.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM pari@mgh-ita.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 BP 1167 EP 1167 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BJ UT WOS:000265387300004 ER PT J AU Lim, R AF Lim, Ruth TI Vesicoureteral Reflux and Urinary Tract Infection: Evolving Practices and Current Controversies in Pediatric Imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE pediatric imaging; radionuclide cystography; renal cortical scintigraphy; ultrasound; urinary tract infection; vesicoureteral reflux; voiding cystourethrography ID INDIRECT RADIONUCLIDE CYSTOGRAPHY; DIMERCAPTOSUCCINIC ACID SCINTIGRAPHY; RENAL CORTICAL SCINTIGRAPHY; ACUTE PYELONEPHRITIS; VOIDING CYSTOURETHROGRAPHY; ANTIBIOTIC-PROPHYLAXIS; ASYMPTOMATIC SIBLINGS; PLANAR PINHOLE; ORAL MIDAZOLAM; YOUNG-CHILDREN AB OBJECTIVE. Pediatric patients with urinary tract infection ( UTI) undergo imaging tests to detect vesicoureteral reflux (VUR) in the belief that VUR correlates to risk of renal scarring. This article describes recent evolution and controversies in the management of UTI and VUR. CONCLUSION. Multitechnique imaging of UTI and VUR is complex and controversial. Evolution in practice patterns is motivated by the desire to rationally minimize unnecessary interventions and radiation exposure. Ongoing evidence-based research is needed to further improve practice guidelines. C1 [Lim, Ruth] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med Mol Imaging, Boston, MA 02114 USA. [Lim, Ruth] Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, Boston, MA 02114 USA. [Lim, Ruth] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lim, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, 34 Fruit St,ELL 237, Boston, MA 02114 USA. EM rlim@partners.org NR 98 TC 34 Z9 36 U1 1 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 BP 1197 EP 1208 DI 10.2214/AJR.08.2187 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BJ UT WOS:000265387300011 PM 19380542 ER PT J AU Boland, GWL AF Boland, Giles W. L. TI Visibility of Radiologists: Helping to Secure Your Future SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material ID TELERADIOLOGY; AGE AB OBJECTIVE. The success of imaging services has been driven, in large part, by radiologists, who arguably became the most visible physicians within their organizations. But this success came at a price, and many groups have sought ways to reduce their traditional responsibilities. In doing so, they have given away one of their strongest assets, their visibility. They now risk being seen as commodities rather than peers-a position that may make them invisible altogether. This article addresses ways to improve these issues. CONCLUSION. Radiologists need to foster professional relationships with all clinical staff, not just physicians. They need to be seen as visible, active, collaborative, and positive participants by all members of the organization. In this way, they can ensure their visibility and continued demand for their services. C1 [Boland, Giles W. L.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Boland, Giles W. L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM gboland@partners.org NR 16 TC 7 Z9 7 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 BP 1373 EP 1374 DI 10.2214/AJR.08.1824 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BJ UT WOS:000265387300032 PM 19380563 ER PT J AU Sangwaiya, MJ Saini, S Blake, MA Dreyer, KJ Kalra, MK AF Sangwaiya, Minal Jagtiani Saini, Shyla Blake, Michael A. Dreyer, Keith J. Kalra, Mannudeep K. TI Errare Humanum Est: Frequency of Laterality Errors in Radiology Reports SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE laterality errors; quality assurance; radiologic errors; radiology reports; side discrepancy ID WRONG-SITE SURGERY AB OBJECTIVE. The purpose of our study was to determine the frequency of discrepancies in side of findings (side discrepancies) in the body and the impression sections of radiology reports. In addition, we determined the frequency of corrected side discrepancies between radiology reports and images in a larger database of radiology reports. MATERIALS AND METHODS. In this cross-sectional study, all radiology reports from January 1, 2007, through December 31, 2007 (n = 1,065,322), that had an addendum were assessed using a radiology reports search engine and searching for the words "left," "right," and "addendum" to locate laterality errors between the body of the report and the impression section. For reports with discrepancies, we recorded the patient's sex, true side of the lesion, and the imaging technique. All reports with an addendum (n = 13,821) in January 2007 containing the words "left" and "right" were evaluated using the same search engine for similar discrepancies. Imaging studies of reports with errors were reviewed to determine the correct side of the lesion and the clinical significance of the errors. RESULTS. Of the 1,065,322 reports, 88 side discrepancies were reported in addenda. The errors in mislabeling the side of the lesion were more common in female (n = 58) than in male (n = 30) patients. Of the 88 errors reported in addenda, 27 were labeled incorrectly in the body of the report, 29 in the impression section, and 32 in both the body and impression sections. In January 2007, 36 of 13,821 (0.26%) reports had no correction for mislabeling of side. Most errors (70.9%) were graded as clinically important. CONCLUSION. Clinically significant errors were found in reporting the body side of the lesion in radiology reports between the body and impression sections. C1 [Sangwaiya, Minal Jagtiani; Saini, Shyla; Blake, Michael A.; Dreyer, Keith J.; Kalra, Mannudeep K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Sangwaiya, MJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Ste 400E, Boston, MA 02114 USA. EM mjagtiani@partners.org NR 9 TC 8 Z9 8 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 BP W239 EP W244 DI 10.2214/AJR.08.1778 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BJ UT WOS:000265387300051 PM 19380530 ER PT J AU Baier, N Reske, S Bohm, B Harisinghani, M AF Baier, N. Reske, S. Boehm, B. Harisinghani, M. TI PET of Medullary Thyroid Cancer: Comparison of FDG, 18F-DOPA and 68Ga-DOTA-TOC in a Cancer Mouse Model SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Baier, N.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Baier, N.; Reske, S.; Boehm, B.] Univ Ulm Klinikum, Ulm, Germany. EM baier.nina@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200233 ER PT J AU Baier, N Bohm, B Reske, S Harisinghani, M AF Baier, N. Boehm, B. Reske, S. Harisinghani, M. TI Somatostatin Analogs in a Colon Carcinoid Cancer Mouse Model: Comparison with FDG and 18F-DOPA SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Baier, N.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Baier, N.; Boehm, B.; Reske, S.] Univ Ulm Klinikum, Ulm, Germany. EM baier.nina@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200232 ER PT J AU Baier, N Hahn, P Gervais, D Mueller, P Samir, A Harisinghani, M AF Baier, N. Hahn, P. Gervais, D. Mueller, P. Samir, A. Harisinghani, M. TI Follow-Up of Initial Nondiagnostic Fine-Needle Aspiration Biopsy: Is Rebiopsy Necessary? Experience in a Cohort of 2,348 Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Baier, N.; Hahn, P.; Gervais, D.; Mueller, P.; Samir, A.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM baier.nina@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200018 ER PT J AU Baier, N Hahn, P Gervais, D Mueller, P Samir, A Harisinghani, M AF Baier, N. Hahn, P. Gervais, D. Mueller, P. Samir, A. Harisinghani, M. TI Reasons for a Nondiagnostic Fine-Needle Aspiration Biopsy in Thyroid Nodules Based on Individual or Combined Ultrasonographic Features SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Baier, N.; Hahn, P.; Gervais, D.; Mueller, P.; Samir, A.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM baier.nina@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200019 ER PT J AU Bajpai, S Singh, A Kambadakone, RA Catalano, O Blake, M Sahani, D AF Bajpai, S. Singh, A. Kambadakone, R. A. Catalano, O. Blake, M. Sahani, D. TI Quantitative Hepatic Imaging: Current and Emerging Trends SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Bajpai, S.; Singh, A.; Kambadakone, R. A.; Catalano, O.; Blake, M.; Sahani, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM surabhibajpai@yahoo.co.in NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200460 ER PT J AU Braschi, M Ramaiya, N Zondervan, R Urban, T Van den Abbeele, A Harris, G AF Braschi, M. Ramaiya, N. Zondervan, R. Urban, T. Van den Abbeele, A. Harris, G. TI Tumor Response Criteria: What Should a Radiologist Know? (CME Credit Available) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Braschi, M.; Zondervan, R.; Urban, T.; Harris, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ramaiya, N.; Van den Abbeele, A.] Dana Farber Hosp, Boston, MA USA. EM mbraschi@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200386 ER PT J AU Chew, M Holalkere, N Guimaraes, A Hahn, P Lee, S AF Chew, M. Holalkere, N. Guimaraes, A. Hahn, P. Lee, S. TI Pelvic Lymph Node Staging of Gynecological Malignancy with Diffusion-Weighted MRI SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Chew, M.; Guimaraes, A.; Hahn, P.; Lee, S.] Massachusetts Gen Hosp, Cambridge, MA USA. [Holalkere, N.] Boston Med Ctr, Boston, MA USA. EM mal_chewbacca@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200097 ER PT J AU Choi, E Patel, M Batra, P Verma, R Jude, C AF Choi, E. Patel, M. Batra, P. Verma, R. Jude, C. TI Back to Basics: The Language of Signs in Thoracic Radiology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Choi, E.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Batra, P.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. [Patel, M.; Verma, R.; Jude, C.] Olive View UCLA Med Ctr, Los Angeles, CA USA. EM matilda@pol.net NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200322 ER PT J AU Cronin, C Catalano, O Blake, M Mueller, P Sahani, O AF Cronin, C. Catalano, O. Blake, M. Mueller, P. Sahani, O. TI PET-CT of the Pancreas: Lesion Detection, Characterization, Surgical Planning and Response Assessment SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Cronin, C.; Catalano, O.; Blake, M.; Mueller, P.; Sahani, O.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM carmelcronin2000@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200474 ER PT J AU Cronin, C Hahn, P Gervais, D Arellano, R Guimaraes, A Levis, D Mueller, P AF Cronin, C. Hahn, P. Gervais, D. Arellano, R. Guimaraes, A. Levis, D. Mueller, P. TI Musculoskeletal Abscess: Effectiveness of Percutaneous Catheter Drainage SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Cronin, C.; Hahn, P.; Gervais, D.; Arellano, R.; Guimaraes, A.; Levis, D.; Mueller, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM carmelcronin2000@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200210 ER PT J AU Dang, P Kalra, M Sack, D Schweitzer, A Dreyer, K AF Dang, P. Kalra, M. Sack, D. Schweitzer, A. Dreyer, K. TI How to Select the Best PACS Solution for Your Institution SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Dang, P.; Kalra, M.; Sack, D.; Schweitzer, A.; Dreyer, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pragya.dang@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200364 ER PT J AU Ghoshhajra, B Blankstein, R Rocha, J Shturman, L Pien, H Rogers, I Okada, D Brady, T Cury, R AF Ghoshhajra, B. Blankstein, R. Rocha-Filho, J. Shturman, L. Pien, H. Rogers, I Okada, D. Brady, T. Cury, R. TI Analysis of Artifacts in Myocardial Perfusion CT: A Preliminary Experience (CME Credit Available) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Ghoshhajra, B.; Blankstein, R.; Rocha-Filho, J.; Shturman, L.; Pien, H.; Rogers, I; Okada, D.; Brady, T.; Cury, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cury, R.] Baptist Cardiac & Vasc Inst, Miami, FL USA. EM ghoshhajra@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200295 ER PT J AU Goud, A Goud, N Jati, A Manuel, D AF Goud, A. Goud, N. Jati, A. Manuel, D. TI Bowel Transit Delay? Switch Planes! Utilizing MDCT and Multi-planar Reformations to Identify Transition Points in Small Bowel Obstruction (CME Credit Available) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Goud, A.; Goud, N.; Jati, A.; Manuel, D.] VA Boston Healthcare Syst, Boston, MA USA. EM cars33@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200415 ER PT J AU Goud, N Jati, A Goud, A Ramaiya, N AF Goud, N. Jati, A. Goud, A. Ramaiya, N. TI The Vermiform Appendix: The Worm That Turned (CME Credit Available) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Goud, N.; Jati, A.; Goud, A.] VA Boston Hlth Care Syst, W Roxbury, MA USA. [Ramaiya, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM anupma.jati@va.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200399 ER PT J AU Islam, T Braschi, M Oliveira, G Harisinghani, M AF Islam, T. Braschi, M. Oliveira, G. Harisinghani, M. TI Quiz Yourself in Lymph Node Characterization With Lymphotropic Nanoparticle-Enhanced MRI Using Superparamagnetic Iron Oxides! (CME Credit Available) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Islam, T.; Braschi, M.; Harisinghani, M.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. EM Islam.Tina@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200716 ER PT J AU Islam, T MacDonald, S Oliveira, G Wolfgang, J Taghian, A Harisinghani, M AF Islam, T. MacDonald, S. Oliveira, G. Wolfgang, J. Taghian, A. Harisinghani, M. TI Nodal Mapping for Radiation Planning in Primary Breast Cancer Using Cross Modality Fusion SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Islam, T.; Harisinghani, M.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. EM Islam.Tina@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200289 ER PT J AU Islam, T Hahn, P Harisinghani, M AF Islam, T. Hahn, P. Harisinghani, M. TI Decreased Uptake of Ferumoxtran-10 in Inguinal Lymph Nodes in Lymphotropic Nanoparticle-Enhanced MRI SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Islam, T.; Harisinghani, M.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. EM Islam.Tina@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200095 ER PT J AU Jagtiani, M Kalra, M Dreyer, K Schirmacher, H Sack, D Saini, S AF Jagtiani, M. Kalra, M. Dreyer, K. Schirmacher, H. Sack, D. Saini, S. TI Thin Client Servers: Technical Aspects, Applications, Advantages and Limitations (CME Credit Available) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Jagtiani, M.; Kalra, M.; Dreyer, K.; Sack, D.; Saini, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mjagtiani@partners.org NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200363 ER PT J AU Jagtiani, M Kalra, M Sahani, D Cushing, M Schirmacher, H Saini, S AF Jagtiani, M. Kalra, M. Sahani, D. Cushing, M. Schirmacher, H. Saini, S. TI Improved Evaluation of the Adrenal Gland at MDCT Using Thin-Client PACS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Jagtiani, M.; Kalra, M.; Sahani, D.; Cushing, M.; Saini, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mjagtiani@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200061 ER PT J AU Jati, A AF Jati, A. TI Fat Containing Lesions of the Abdomen and Pelvis: CT and MRI SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Jati, A.] VA Boston Hlth Care Syst, W Roxbury, MA USA. EM anupma.jati@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200490 ER PT J AU Kambadakone, A Samir, A Eisner, B Saini, S Sahani, D AF Kambadakone, A. Samir, A. Eisner, B. Saini, S. Sahani, D. TI Subtraction CT: Is There a Role in the Characterization of Renal Lesions? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Kambadakone, A.; Samir, A.; Eisner, B.; Saini, S.; Sahani, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM akambadakone@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200044 ER PT J AU Kligerman, S Abbott, G Fidias, P Neal, J AF Kligerman, S. Abbott, G. Fidias, P. Neal, J. TI A Radiologist's Guide to the Revised Staging System for Nonsmall Cell Lung Cancer (CME Credit Available) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Kligerman, S.; Abbott, G.; Fidias, P.; Neal, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM skligerman@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200328 ER PT J AU Levenson, R Pearson, K Saokar-Rebello, A Lee, S Mueller, P Hahn, P AF Levenson, R. Pearson, K. Saokar-Rebello, A. Lee, S. Mueller, P. Hahn, P. TI Image-Guided Drainage of Tubo-Ovarian Abscesses: How Often Do We Succeed? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Levenson, R.; Pearson, K.; Lee, S.; Mueller, P.; Hahn, P.] Massachusetts Gen Hosp, Cambridge, MA USA. [Saokar-Rebello, A.] Boston Univ, Med Ctr, Boston, MA USA. EM rbl500@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200099 ER PT J AU Ma, X Sahani, D Gervais, D Hahn, P Mueller, P AF Ma, X. Sahani, D. Gervais, D. Hahn, P. Mueller, P. TI Hepatic Lesions Imitating Neoplasms on Advanced Imaging (CT/MR/PET) - Experience in 74 Patients with Percutaneous Image-Guided Biopsy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Ma, X.; Sahani, D.; Gervais, D.; Hahn, P.; Mueller, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM xma@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200241 ER PT J AU Ma, X Sahani, D Arellano, R Gervais, D Hahn, P Mueller, P AF Ma, X. Sahani, D. Arellano, R. Gervais, D. Hahn, P. Mueller, P. TI Experience with Percutaneous Image-Guided Pancreatic Biopsy in 124 Solid and Cystic Lesion SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Ma, X.; Sahani, D.; Arellano, R.; Gervais, D.; Hahn, P.; Mueller, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM xma@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200169 ER PT J AU Marentis, T Jagtiani, SM Stecker, M Walker, T Wicky, S Kalva, S AF Marentis, T. Jagtiani, Sangwaiya M. Stecker, M. Walker, T. Wicky, S. Kalva, S. TI Safety, Efficacy and Retrievability of the "Optease" Vena Cava Filters: Experience with 71 Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Marentis, T.; Jagtiani, Sangwaiya M.; Stecker, M.; Walker, T.; Wicky, S.; Kalva, S.] Harvard Univ, Sch Med, Boston, MA USA. [Jagtiani, Sangwaiya M.; Walker, T.; Wicky, S.; Kalva, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stecker, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. EM mjagtiani@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200080 ER PT J AU McCarten, K Rosen, N Friedman, D Schwartz, C Voss, S Bishop-Jodoin, M Kessel, S Johnson, C Laurie, F FitzGerald, T AF McCarten, K. Rosen, N. Friedman, D. Schwartz, C. Voss, S. Bishop-Jodoin, M. Kessel, S. Johnson, C. Laurie, F. FitzGerald, T. TI Feasibility of Real-Time Diagnostic Imaging Central Review in Multicenter Cancer Trials SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [McCarten, K.; Schwartz, C.] Rhode Isl Hosp, Providence, RI USA. [McCarten, K.; Rosen, N.; Bishop-Jodoin, M.; Kessel, S.; Johnson, C.; Laurie, F.; FitzGerald, T.] Univ Massachusetts, Sch Med, Qual Assurance Review Ctr, Providence, RI USA. [Friedman, D.] Vanderbilt Childrens Hosp, Nashville, TN USA. [Voss, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Voss, S.] Childrens Hosp, Boston, MA 02115 USA. EM MJodoin@QARC.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200076 ER PT J AU Motamedi, D Modarresi, S Masih, S AF Motamedi, D. Modarresi, S. Masih, S. TI Illustrative Review of Superior Labral Anterior-Posterior Lesions of the Shoulder: Patterns and Pitfalls (CME Credit Available) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Motamedi, D.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Modarresi, S.; Masih, S.] Univ Calif Los Angeles, Vet Adm Greater Los Angeles, Los Angeles, CA USA. EM dariamot@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200592 ER PT J AU Oliveira, G Zondervan, R Harris, G Hodge, S Harisinghani, M AF Oliveira, G. Zondervan, R. Harris, G. Hodge, S. Harisinghani, M. TI Treatment Response with Ca-125 in Ovarian Cancer Patients: Comparison among RECIST, WHO, Tridimensional and 3D Volumetric Criteria SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Oliveira, G.] Univ Washington, Seattle, WA 98195 USA. [Zondervan, R.; Harris, G.; Hodge, S.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM grachid@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200150 ER PT J AU Ramesh, AK Singh, A Willingham, F Gee, D Sylla, P Mino-Kenudson, M Rattner, D Brugge, W Sahani, D AF Ramesh, Kambadakone A. Singh, A. Willingham, F. Gee, D. Sylla, P. Mino-Kenudson, M. Rattner, D. Brugge, W. Sahani, D. TI 64-Slice MDCT as a Surrogate End Point for the Postoperative Evaluation of Laparoscopic and Natural Orifice Transluminal Endoscopic Distal Pancreatectomy in a Porcine Model SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Ramesh, Kambadakone A.; Singh, A.; Willingham, F.; Gee, D.; Sylla, P.; Mino-Kenudson, M.; Rattner, D.; Brugge, W.; Sahani, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM akambadakone@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200170 ER PT J AU Ramesh, AK Eisner, B Dretler, D Sahani, D AF Ramesh, Kambadakone A. Eisner, B. Dretler, D. Sahani, D. TI Measurement of Stone Size on CT: Effect of Window Settings and Magnification in an In-Vitro Study SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Ramesh, Kambadakone A.; Eisner, B.; Dretler, D.; Sahani, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM akambadakone@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200041 ER PT J AU Rosenthal, P AF Rosenthal, P. TI Paranasal Sinus Disease in Multiple Sclerosis-Possible Links to Periodontal Disease and Parallels to this in Other Autoimmune Diseases (CME Credit Available) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Rosenthal, P.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. EM peter.rosenthal@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200679 ER PT J AU Sahani, D Chen, K Kuhn, M Chen, N Heiken, J Soulez, G Reimer, D AF Sahani, D. Chen, K. Kuhn, M. Chen, N. Heiken, J. Soulez, G. Reimer, D. TI Incidence of Contrast-Induced Nephropathy Following Intravenous Injection in a Large Population of Patients with Chronic Kidney Disease Undergoing CT Imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Sahani, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chen, K.] Rui Jin Hosp, Shanghai, Peoples R China. [Kuhn, M.] So Illinois Univ, Sch Med, Springfield, IL USA. [Chen, N.] Shanghai Jiao Tong Univ, Shanghai 200030, Peoples R China. [Heiken, J.] Washington Univ, St Louis, MO USA. [Soulez, G.] Univ Montreal, Montreal, PQ, Canada. [Reimer, D.] Radiologists PC, Mobile, AL USA. EM dsahani@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200046 ER PT J AU Sainani, N Catalano, O Mino-Kenudson, M Forcione, D Sahani, D AF Sainani, N. Catalano, O. Mino-Kenudson, M. Forcione, D. Sahani, D. TI Imaging Approach to Lesions of Pancreatic Groove With Radiologic-Pathologic Correlation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Sainani, N.; Catalano, O.; Mino-Kenudson, M.; Forcione, D.; Sahani, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM drnisainani@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200470 ER PT J AU Sainani, N Fritz, S Mino-Kenudson, M Fernandez-del Castillo, C Sahani, D AF Sainani, N. Fritz, S. Mino-Kenudson, M. Fernandez-del Castillo, C. Sahani, D. TI Can Dimensions of the Pancreatic Duct or Cyst Communication Stratify Intraductal Papillary Mucinous Neoplasms into Branch Duct Type from Combined? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Sainani, N.; Fritz, S.; Mino-Kenudson, M.; Fernandez-del Castillo, C.; Sahani, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM drnisainani@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200168 ER PT J AU Sangwaiya, MJ Saini, S Blake, M Dreyer, K Kalra, M AF Sangwaiya, Jagtiani M. Saini, S. Blake, M. Dreyer, K. Kalra, M. TI To Err is Human: How to Avoid Errors of Laterality in Radiology Reports SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Sangwaiya, Jagtiani M.; Saini, S.; Blake, M.; Dreyer, K.; Kalra, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mjagtiani@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200012 ER PT J AU Singh, S Jagtiani, M Blake, M Thomas, S Joshi, M Kalra, M AF Singh, S. Jagtiani, M. Blake, M. Thomas, S. Joshi, M. Kalra, M. TI Role of an Advanced Statistical Iterative Reconstruction Technique for Improving the Image Quality of Low Radiation Dose CT (CME Credit Available) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Singh, S.; Jagtiani, M.; Blake, M.; Thomas, S.; Kalra, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ssingh6@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200371 ER PT J AU Singh, S Kalra, M Sjoberg, J Sahani, D Blake, M AF Singh, S. Kalra, M. Sjoberg, J. Sahani, D. Blake, M. TI Application of an Adaptive Nonlinear Postprocessing Filter for Improving the Image Quality of Low Radiation Dose CT: A Double Blinded Comparative Study SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Singh, S.; Kalra, M.; Sahani, D.; Blake, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sjoberg, J.] SharpView AB, Linkoping, Sweden. EM ssingh6@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200174 ER PT J AU Singh, S Kalra, M Forsberg, A Toth, T Blake, M AF Singh, S. Kalra, M. Forsberg, A. Toth, T. Blake, M. TI Application of Noise Projection Software and 2D Nonlinear Adaptive Filters for Radiation Dose Reduction with a Renal Calculus CT Protocol SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Singh, S.; Kalra, M.; Blake, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Forsberg, A.] Sharpview AB, Linkoping, Sweden. [Toth, T.] GE Co, Waukesha, WI USA. EM ssingh6@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200040 ER PT J AU Small, J Haacke, E Schaefer, P AF Small, J. Haacke, E. Schaefer, P. TI Susceptibility Imaging and Stroke SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Small, J.; Schaefer, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Haacke, E.] Wayne State Univ, Detroit, MI USA. EM jsmall1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200654 ER PT J AU Souza, F Ramaiya, N Johnston, C Jagannathan, J Ros, P AF Souza, F. Ramaiya, N. Johnston, C. Jagannathan, J. Ros, P. TI Radiological Manifestations of Recurrent Malignant Peritoneal Mesothelioma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Souza, F.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Souza, F.; Ramaiya, N.; Johnston, C.; Jagannathan, J.; Ros, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM ffsouza@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200224 ER PT J AU Souza, F Di Salvo, D Ramayia, N AF Souza, F. Di Salvo, D. Ramayia, N. TI Venous Thrombosis in Outpatient Oncology Patients: Distribution, Type, and Comorbidities SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Souza, F.; Di Salvo, D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Souza, F.; Di Salvo, D.; Ramayia, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM ffsouza@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200081 ER PT J AU Kempster, GB Gerratt, BR Abbott, KV Barkmeier-Kraemer, J Hillman, RE AF Kempster, Gail B. Gerratt, Bruce R. Abbott, Katherine Verdolini Barkmeier-Kraemer, Julie Hillman, Robert E. TI Consensus Auditory-Perceptual Evaluation of Voice: Development of a Standardized Clinical Protocol SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE Consensus Auditory-Perceptual Evaluation of Voice; voice; voice assessment ID INDIVIDUAL-DIFFERENCES; QUALITY; RELIABILITY; SCALE; GRBAS AB Purpose: This article presents the development of the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) following a consensus conference on perceptual voice quality measurement sponsored by the American Speech-Language-Hearing Association's Special Interest Division 3, Voice and Voice Disorders. The CAPE-V protocol and recording form were designed to promote a standardized approach to evaluating and documenting auditory-perceptual judgments of vocal quality. Method: A summary of the consensus conference proceedings and the factors considered by the authors in developing this instrument are included. Conclusion: The CAPE-V form and instructions, included as appendices to this article, enable clinicians to document perceived voice quality deviations following a standard (i.e., consistent and specified) protocol. C1 [Kempster, Gail B.] Rush Univ, Med Ctr, Dept Commun Disorders & Sci, Chicago, IL 60612 USA. [Gerratt, Bruce R.] Univ Calif Los Angeles, Los Angeles, CA USA. [Abbott, Katherine Verdolini] Univ Pittsburgh, Pittsburgh, PA USA. [Barkmeier-Kraemer, Julie] Univ Arizona, Tucson, AZ USA. [Hillman, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kempster, GB (reprint author), Rush Univ, Med Ctr, Dept Commun Disorders & Sci, 1653 W Congress Pkwy,203 Senn, Chicago, IL 60612 USA. EM gail_b_kempster@rush.edu OI Gerratt, Bruce/0000-0001-7032-1051 NR 30 TC 170 Z9 176 U1 0 U2 10 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD MAY PY 2009 VL 18 IS 2 BP 124 EP 132 DI 10.1044/1058-0360(2008/08-0017) PG 9 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 442UB UT WOS:000265865000003 PM 18930908 ER PT J AU Narayana, S Jacks, A Robin, DA Poizner, H Zhang, W Franklin, C Liotti, M Vogel, D Fox, PT AF Narayana, Shalini Jacks, Adam Robin, Donald A. Poizner, Howard Zhang, Wei Franklin, Crystal Liotti, Mario Vogel, Deanie Fox, Peter T. TI A Noninvasive Imaging Approach to Understanding Speech Changes Following Deep Brain Stimulation in Parkinson's Disease SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE Parkinson's disease; neuroimaging; deep brain stimulation; transcranial magnetic stimulation ID SUBTHALAMIC NUCLEUS STIMULATION; TRANSCRANIAL MAGNETIC STIMULATION; BILATERAL STIMULATION; PALLIDOTOMY SURGERY; NETWORK MODULATION; MOTOR CONTROL; ORAL CONTROL; DYSARTHRIA; DISORDER; LANGUAGE AB Purpose: To explore the use of noninvasive functional imaging and "virtual" lesion techniques to study the neural mechanisms underlying motor speech disorders in Parkinson's disease. Here, we report the use of positron emission tomography (PET) and transcranial magnetic stimulation (TMS) to explain exacerbated speech impairment following subthalamic nucleus deep brain stimulation (STN-DBS) in a patient with Parkinson's disease. Method: Perceptual and acoustic speech measures, as well as cerebral blood flow during speech as measured by PET, were obtained with STN-DBS on and off. TMS was applied to a region in the speech motor network found to be abnormally active during DBS. Speech disruption by TMS was compared both perceptually and acoustically with speech produced with DBS on. Results: Speech production was perceptually inferior and acoustically less contrastive during left STN stimulation compared to no stimulation. Increased neural activity in left dorsal premotor cortex (PMd) was observed during IDBS on. "Virtual" lesioning of this region resulted in speech characterized by decreased speech segment duration, increased pause duration, and decreased intelligibility. Conclusions: This case report provides evidence that impaired speech production accompanying STN-DBS may result from unintended activation of PMd. Clinical application of functional imaging and TMS may lead to optimizing the delivery of STN-DBS to improve outcomes for speech production as well as general motor abilities. C1 [Narayana, Shalini; Jacks, Adam; Robin, Donald A.; Zhang, Wei; Franklin, Crystal; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, San Antonio, TX 78229 USA. [Robin, Donald A.] Univ Texas San Antonio, Honors Coll, San Antonio, TX USA. [Poizner, Howard] Univ Calif San Diego, Inst Neural Computat, San Diego, CA 92103 USA. [Liotti, Mario] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Fox, Peter T.] S Texas Vet Hlth Care Ctr, San Antonio, TX USA. [Vogel, Deanie] Our Lady Lake Univ, San Antonio, TX USA. RP Narayana, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, 7703 Floyd Curl Dr MSC 6240, San Antonio, TX 78229 USA. EM narayana@uthscsa.edu RI Fox, Peter/B-4725-2010; Robin, Donald/F-2109-2010; Narayana, Shalini/F-3031-2010; Jacks, Adam/I-3644-2013 OI Fox, Peter/0000-0002-0465-2028; Jacks, Adam/0000-0001-6358-2878 FU NIDCD NIH HHS [R01 DC001150, R01 DC001150-17]; NIMH NIH HHS [MH60246, R01 MH060246-02, R01 MH074457, R01 MH060246, R01 MH060246-01, R01 MH060246-03]; NINDS NIH HHS [NS36449, R01 NS036449-08, R21 NS043738, R21 NS043738-01, NS43738, R01 NS036449, R21 NS043738-02, R56 NS036449, R56 NS036449-09A1] NR 84 TC 31 Z9 31 U1 2 U2 5 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD MAY PY 2009 VL 18 IS 2 BP 146 EP 161 DI 10.1044/1058-0360(2008/08-0004) PG 16 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 442UB UT WOS:000265865000005 PM 19029533 ER PT J AU Gadikota, HR Seon, JK Kozanek, M Oh, LS Gill, TJ Montgomery, KD Li, G AF Gadikota, Hemanth R. Seon, Jong Keun Kozanek, Michal Oh, Luke S. Gill, Thomas J. Montgomery, Kenneth D. Li, Guoan TI Biomechanical Comparison of Single-Tunnel-Double-Bundle and Single-Bundle Anterior Cruciate Ligament Reconstructions SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE anterior cruciate ligament (ACL); knee kinematics; single-tunnel-double-bundle ACL reconstruction; robotic testing ID INITIAL GRAFT TENSION; HAMSTRING TENDON GRAFTS; SIMULATED MUSCLE LOADS; PATELLAR TENDON; LONG-TERM; SEMITENDINOSUS TENDON; ANATOMIC RECONSTRUCTION; POSTEROLATERAL BUNDLES; ACL RECONSTRUCTION; KNEE KINEMATICS AB Background: Anatomic double-bundle reconstruction has been thought to better simulate the anterior cruciate ligament anatomy. It is, however, a technically challenging procedure, associated with longer operation time and higher cost. Hypothesis: Double-bundle anterior cruciate ligament reconstruction using a single femoral and tibial tunnel can closely reproduce intact knee kinematics. Study Design: Controlled laboratory study. Methods: Eight fresh-frozen human cadaveric knee specimens were tested using a robotic testing system to investigate the kinematic response of the knee joint under an anterior tibial load (130 N), simulated quadriceps load (400 N), and combined torques (5 N.m valgus and 5 N.m internal tibial torques) at 0 degrees, 15 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion. Each knee was tested sequentially under 4 conditions: (1) anterior cruciate ligament intact, (2) anterior cruciate ligament deficient, (3) single-bundle anterior cruciate ligament reconstruction using quadrupled hamstring tendon, and (4) single-tunnel-double-bundle anterior cruciate ligament reconstruction using the same tunnels and quadrupled hamstring tendon graft as in the single-bundle anterior cruciate ligament reconstruction. Results: Single-tunnel-double-bundle anterior cruciate ligament reconstruction more closely restored the intact knee kinematics than single-bundle anterior cruciate ligament reconstruction at low flexion angles (= 30) under the anterior tibial load and simulated muscle load (P < .05). However, single-tunnel-double-bundle anterior cruciate ligament reconstruction overconstrained the knee joint at high flexion angles (>= 60) under the anterior tibial load and at 0 degrees and 30 degrees of flexion under combined torques. Conclusion: This double-bundle anterior cruciate ligament reconstruction using a single tunnel can better restore anterior tibial translations to the intact level compared with single-bundle anterior cruciate ligament reconstruction at low flexion angles, but it overconstrained the knee joint at high flexion angles. Clinical Relevance: This technique could be an alternative for both single-bundle and double-tunnel-double-bundle anterior cruciate ligament reconstructions to reproduce intact knee kinematics and native anterior cruciate ligament anatomy. C1 [Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. [Seon, Jong Keun] Chonnam Natl Univ, Hwasun Hosp, Dept Orthopaed, Jeonnam, South Korea. [Montgomery, Kenneth D.] Tri Cty Orthopaed & Sports Med, Morristown, NJ USA. RP Li, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org OI Oh, Luke/0000-0002-6610-8204 FU NIAMS NIH HHS [AR 055612, R01 AR055612] NR 48 TC 25 Z9 34 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD MAY PY 2009 VL 37 IS 5 BP 962 EP 969 DI 10.1177/0363546508330145 PG 8 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 440GU UT WOS:000265689600015 PM 19261901 ER PT J AU Javid, SH Smith, BL Mayer, E Bellon, J Murphy, CD Lipsitz, S Golshan, M AF Javid, Sara H. Smith, Barbara L. Mayer, Erica Bellon, Jennifer Murphy, Colleen D. Lipsitz, Stuart Golshan, Mehra TI Tubular carcinoma of the breast: results of a large contemporary series SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Breast-conservation surgery; Invasive ductal carcinoma; Tubular carcinoma ID METASTASES; PURE AB BACKGROUND: Tubular carcinoma (TC) of the breast is an uncommon subtype associated with a favorable prognosis. This study aimed to assess recent trends and prognostic features in the treatment of TC. METHODS: We performed a retrospective review of cases of TC of the breast treated between 1997 and 2004. RESULTS: We identified 111 cases of TC of the breast. The median patient age at diagnosis was 55 years, and the median follow-up period was 72 months. Breast-conservation surgery was performed in 75% (83 of 111) of patients. Axillary staging was performed in 80% (89 of 111). Nine (8.1%) were found to be node-positive. Node positivity was associated with larger tumor size (P = .003). All node-positive tumors were greater than 1 cm. One patient developed an in-breast recurrence. No patient developed distant metastases or died from breast cancer. CONCLUSIONS: In this series of TC, the locoregional recurrence rate was low and no patient developed distant metastases. Surgical staging of the axilla may not be necessary in lesions measuring 1 cm or less. (C) 2009 Elsevier Inc. All rights reserved. C1 [Javid, Sara H.; Murphy, Colleen D.; Lipsitz, Stuart; Golshan, Mehra] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. [Javid, Sara H.; Smith, Barbara L.; Murphy, Colleen D.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mayer, Erica] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Bellon, Jennifer] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 13 TC 16 Z9 20 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 2009 VL 197 IS 5 BP 674 EP 677 DI 10.1016/j.amjsurg.2008.05.005 PG 4 WC Surgery SC Surgery GA 442SB UT WOS:000265859800025 PM 18789411 ER PT J AU Knosalla, C Yazawa, K Behdad, A Bodyak, N Shang, H Buhler, L Houser, S Gollackner, B Griesemer, A Schmitt-Knosalla, I Schuurman, HJ Awwad, M Sachs, DH Cooper, DKC Yamada, K Usheva, A Robson, SC AF Knosalla, C. Yazawa, K. Behdad, A. Bodyak, N. Shang, H. Buehler, L. Houser, S. Gollackner, B. Griesemer, A. Schmitt-Knosalla, I. Schuurman, H. -J. Awwad, M. Sachs, D. H. Cooper, D. K. C. Yamada, K. Usheva, A. Robson, S. C. TI Renal and Cardiac Endothelial Heterogeneity Impact Acute Vascular Rejection in Pig-to-Baboon Xenotransplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Gene expression; heart; kidney; vasculature; xenotransplantation ID DISSEMINATED INTRAVASCULAR COAGULATION; HYPERACUTE LUNG REJECTION; XENOGRAFT REJECTION; HEART-TRANSPLANTATION; ANTI-GAL-ALPHA-1-3GAL ANTIBODY; THERAPEUTIC STRATEGIES; KIDNEY-TRANSPLANTATION; ORGAN-TRANSPLANTATION; TOLERANCE INDUCTION; ALLOGRAFT REJECTION AB Xenograft outcomes are dictated by xenoantigen expression, for example, Gal alpha 1, 3Gal (Gal), but might also depend on differing vascular responses. We investigated whether differential vascular gene expression in kidney and cardiac xenografts correlate with development of thrombotic microangiopathy (TM) and consumptive coagulation (CC). Immunosuppressed baboons underwent miniswine or hDAF pig kidney (n = 6) or heart (n = 7), or Gal-transferase gene-knockout (GalT-KO) (thymo)kidney transplantation (n = 14). Porcine cDNA miniarrays determined donor proinflammatory, apoptosis-related and vascular coagulant/fibrinolytic gene expression at defined time points; validated by mRNA, protein levels and immunopathology. hDAF-transgenic and GalT-KO xenografts, (particularly thymokidneys) exhibited prolonged survival. CC was seen with Gal-expressing porcine kidneys (3 of 6), only 1 of 7 baboons postcardiac xenotransplantation and was infrequent following GalT-KO grafts (1 of 14). Protective-type genes (heme oxygenase-I, superoxide dismutases and CD39) together with von Willebrand factor and P-selectin were upregulated in all renal grafts. Transcriptional responses in Gal-expressing xenografts were comparable to those seen in the infrequent GalT-KO rejection. In cardiac xenografts, fibrin deposition was associated with increased plasminogen activator inhibitor-1 expression establishing that gene expression profiles in renal and cardiac xenografts differ in a quantitative manner. These findings suggest that therapeutic targets may differ for renal and cardiac xenotransplants. C1 [Behdad, A.; Shang, H.; Robson, S. C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Transplantat Ctr, Boston, MA 02215 USA. [Behdad, A.; Shang, H.; Robson, S. C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Liver, Boston, MA 02215 USA. [Knosalla, C.; Yazawa, K.; Buehler, L.; Gollackner, B.; Griesemer, A.; Sachs, D. H.; Cooper, D. K. C.; Yamada, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02215 USA. [Bodyak, N.; Usheva, A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol,Dept Med, Boston, MA 02215 USA. [Houser, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Schmitt-Knosalla, I.] Harvard Univ, Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Sch Med, Boston, MA 02215 USA. [Schuurman, H. -J.; Awwad, M.] Immerge BioTherapeut, Cambridge, MA USA. RP Robson, SC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Transplantat Ctr, Boston, MA 02215 USA. EM srobson@bimc.harvard.edu FU NHLBI NIH HHS [P01 HL076540]; NIAID NIH HHS [P01 AI045897, P01 AI045897-01A10003, U01 AI066331, U01 AI066331-01] NR 56 TC 29 Z9 30 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2009 VL 9 IS 5 BP 1006 EP 1016 DI 10.1111/j.1600-6143.2009.02602.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 433QZ UT WOS:000265222200006 PM 19422330 ER PT J AU Knechtle, SJ Pascual, J Bloom, DD Torrealba, JR Jankowska-Gan, E Burlingham, WJ Kwun, J Colvin, RB Seyfert-Margolis, V Bourcier, K Sollinger, HW AF Knechtle, S. J. Pascual, J. Bloom, D. D. Torrealba, J. R. Jankowska-Gan, E. Burlingham, W. J. Kwun, J. Colvin, R. B. Seyfert-Margolis, V. Bourcier, K. Sollinger, H. W. TI Early and Limited Use of Tacrolimus to Avoid Rejection in an Alemtuzumab and Sirolimus Regimen for Kidney Transplantation: Clinical Results and Immune Monitoring SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Alemtuzumab; immune monitoring; immunosuppression; kidney; transplantation ID DOSE CYCLOSPORINE MONOTHERAPY; RENAL-ALLOGRAFT RECIPIENTS; REGULATORY T-CELLS; CAMPATH 1H; MYCOPHENOLATE-MOFETIL; LIVER-TRANSPLANTATION; OPERATIONAL TOLERANCE; INDUCTION THERAPY; PERIPHERAL-BLOOD; RANDOMIZED-TRIAL AB Alemtuzumab induction with 60 days of tacrolimus treatment and continuous sirolimus treatment prevented acute rejection in nine of 10 consecutive renal allograft recipients. All patients are alive with a functioning kidney graft at 27-39 months of follow-up. Extensive immune monitoring was performed in all patients. Alloantibody detection, cytokine kinetics assay (CKA), and trans vivo delayed-type hypersensitivity (DTH) assay were performed every 6 months showing correlation with clinical evolution. Despite alloantibody presence in five patients, eight patients remain without the need for specific treatment and only sirolimus monotherapy in decreasing dosage. Four patients take only 1 mg sirolimus daily with levels of 3-4 ng/mL. One patient showed clinical signs of rejection at month 9 post-transplant, with slow increase in serum creatinine and histological signs of mixed cellular (endarteritis) and humoral rejection (C4d positivity in peritubular capillaries and donor-specific antibody (DSA)). In summary, the addition of tacrolimus therapy for 2 months to a steroid-free, alemtuzumab induction and sirolimus maintenance protocol limited the previously shown acute rejection development. Nevertheless, alloantibody was present in serum and/or C4d present on 1-year biopsy in half the patients. The combination of CKA and DSA monitoring or the performance of transvivo DTH correlated with immune status of the patients. C1 [Knechtle, S. J.; Pascual, J.; Bloom, D. D.; Jankowska-Gan, E.; Burlingham, W. J.; Kwun, J.; Sollinger, H. W.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Torrealba, J. R.] Univ Wisconsin, Dept Pathol & Lab Med, Sch Med & Publ Hlth, Madison, WI USA. [Colvin, R. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seyfert-Margolis, V.; Bourcier, K.] Immune Tolerance Network, Bethesda, MD USA. RP Knechtle, SJ (reprint author), Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM stuart.knechtle@emoryhealthcare.org RI ieong, bee/C-5840-2012 NR 36 TC 46 Z9 48 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2009 VL 9 IS 5 BP 1087 EP 1098 DI 10.1111/j.1600-6143.2009.02581.x PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA 433QZ UT WOS:000265222200015 PM 19344431 ER PT J AU Gore, JL Danovitch, GM Litwin, MS Pham, PTT Singer, JS AF Gore, J. L. Danovitch, G. M. Litwin, M. S. Pham, P-T. T. Singer, J. S. TI Disparities in the Utilization of Live Donor Renal Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Access to transplantation; kidney transplantation; live donor transplantation; racial and ethnic disparities ID LIVING KIDNEY DONATION; AFRICAN-AMERICANS; ORGAN DONATION; UNITED-STATES; RACIAL DISPARITIES; HEALTH RESEARCH; ACCESS; WILLINGNESS; NEPHRECTOMY; EXPERIENCE AB Despite universal payer coverage with Medicare, sociodemographic disparities confound the care of patients with renal failure. We sought to determine whether adults who realize access to kidney transplantation suffer inequities in the utilization of live donor renal transplantation (LDRT). We identified adults undergoing primary renal transplantation in 2004-2006 from the United Network for Organ Sharing (UNOS). We modeled receipt of live versus deceased donor renal transplant on multilevel multivariate models that examined recipient, center and UNOS region-specific covariates. Among 41 090 adult recipients identified, 39% underwent LDRT. On multivariate analysis, older recipients (OR 0.62, 95% CI 0.56-0.68 for 50-59 year-olds vs. 18-39 year-old recipients), those of African American ethnicity (OR 0.54, 95% CI 0.50-0.59 vs. whites) and of lower socioeconomic status (OR 0.72, 95% CI 0.67-0.79 for high school-educated vs. college-educated recipients; OR 0.78, 95% CI 0.71-0.87 for lowest vs. highest income quartile) had lower odds of LDRT. These characteristics accounted for 14.2% of the variation in LDRT, more than recipient clinical variables, transplant center characteristics and UNOS region level variation. We identified significant racial and socioeconomic disparities in the utilization of LDRT. Educational initiatives and dissemination of processes that enable increased utilization of LDRT may address these disparities. C1 [Gore, J. L.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. [Gore, J. L.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA USA. [Gore, J. L.; Litwin, M. S.; Singer, J. S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Danovitch, G. M.; Pham, P-T. T.] Univ Calif Los Angeles, David Geffen Sch Med, Div Kidney & Pancreas Transplantat, Dept Med, Los Angeles, CA 90095 USA. [Litwin, M. S.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA. RP Gore, JL (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. EM jgore@mednet.ucla.edu OI Gore, John/0000-0002-2847-5062 FU Health Resources and Services Administration [231-00-0115] FX This work was supported in part by Health Resources and Services Administration contract 231-00-0115. The content is the responsibility of the authors alone and 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. The authors have no disclosures to report. NR 36 TC 65 Z9 65 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2009 VL 9 IS 5 BP 1124 EP 1133 DI 10.1111/j.1600-6143.2009.02620.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 433QZ UT WOS:000265222200019 PM 19422338 ER PT J AU Brown, EN Kass, RE AF Brown, Emery N. Kass, Robert E. TI What Is Statistics? SO AMERICAN STATISTICIAN LA English DT Article DE Cross-disciplinary statistical research; Statistical paradigm; Statistical thinking ID 2 CULTURES; FUTURE; EDUCATION; THINKING AB We use our experience in neuroscience as a source of defining issues for the discipline of statistics. We argue that to remain vibrant, the field must open up by taking a less restrictive view of what constitutes statistical training. C1 [Brown, Emery N.] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brown, Emery N.] Harvard Mit Div Hlth Sci & Technol, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Kass, Robert E.] Carnegie Mellon Univ, Dept Stat, Ctr Neural Basis Cognit, Pittsburgh, PA 15217 USA. [Kass, Robert E.] Carnegie Mellon Univ, Machine Learning Dept, Pittsburgh, PA 15217 USA. RP Brown, EN (reprint author), Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM enb@neurostat.mit.edu; kass@stat.cmu.edu NR 37 TC 28 Z9 28 U1 1 U2 11 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0003-1305 J9 AM STAT JI Am. Stat. PD MAY PY 2009 VL 63 IS 2 BP 105 EP 123 DI 10.1198/tast.2009.0019 PG 19 WC Statistics & Probability SC Mathematics GA 477FI UT WOS:000268503600001 ER PT J AU Ficarro, SB Zhang, Y Lu, Y Moghimi, AR Askenazi, M Hyatt, E Smith, ED Boyer, L Schlaeger, TM Luckey, CJ Marto, JA AF Ficarro, Scott B. Zhang, Yi Lu, Yu Moghimi, Ahmadali R. Askenazi, Manor Hyatt, Elzbieta Smith, Eric D. Boyer, Leah Schlaeger, Thorsten M. Luckey, C. John Marto, Jarrod A. TI Improved Electrospray Ionization Efficiency Compensates for Diminished Chromatographic Resolution and Enables Proteomics Analysis of Tyrosine Signaling in Embryonic Stem Cells SO ANALYTICAL CHEMISTRY LA English DT Article ID CAPILLARY LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; INNER DIAMETERS; MU-M; NANOFLOW REGIME; DEFINED FACTORS; SELF-RENEWAL; SRC FAMILY; ION-SOURCE; PROTEINS AB Characterization of signaling pathways in embryonic stem cells is a prerequisite for future application of these cells to treat human disease and other disorders. Identification of tyrosine signaling cascades is of particular interest but is complicated by the relatively low levels of tyrosine phosphorylation in embryonic stem cells. These hurdles correlate with the primary limitations of mass spectrometry-based proteomics; namely, poor detection limit and dynamic range. To overcome these obstacles, we fabricated miniaturized LC-electrospray assemblies that provided similar to 15-fold improvement in LC-MS performance. Significantly, our characterization data demonstrate that electrospray ionization efficiency compensates for diminished chromatographic performance at effluent flow rates below Van Deemter minima. Use of these assemblies. facilitated quantitative proteomics-based analysis of tyrosine signaling cascades in embryonic stem cells. Our results suggest that a renewed focus on miniaturized LC coupled to ultralow flow electrospray will provide a viable path for proteomic analysis of primary. cells and rare post-translational modifications. C1 [Ficarro, Scott B.; Zhang, Yi; Lu, Yu; Moghimi, Ahmadali R.; Askenazi, Manor; Smith, Eric D.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Ficarro, Scott B.; Zhang, Yi; Askenazi, Manor; Smith, Eric D.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA. [Ficarro, Scott B.; Lu, Yu; Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Hyatt, Elzbieta; Luckey, C. John] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Boyer, Leah; Schlaeger, Thorsten M.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Boyer, Leah; Schlaeger, Thorsten M.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Askenazi, Manor] Hebrew Univ Jerusalem, Dept Biol Chem, IL-91905 Jerusalem, Israel. RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 1158A, Boston, MA 02215 USA. EM jarrod_marto@dfci.harvard.edu FU Dana-Farber Cancer Institute; W.M. Keck Foundation FX The first four authors contributed equally to this work. The authors thank David Lange at the Harvard Center for Nanoscale Systems for assistance with acquisition of SEM images. Generous financial support for this work was provided by the Dana-Farber Cancer Institute. J.A.M. acknowledges financial support from the W.M. Keck Foundation. NR 66 TC 58 Z9 59 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAY 1 PY 2009 VL 81 IS 9 BP 3440 EP 3447 DI 10.1021/ac802720e PG 8 WC Chemistry, Analytical SC Chemistry GA 439MY UT WOS:000265632400034 PM 19331382 ER PT J AU Koh, I Hong, R Weissleder, R Josephson, L AF Koh, Isaac Hong, Rui Weissleder, Ralph Josephson, Lee TI Nanoparticle-Target Interactions Parallel Antibody-Protein Interactions SO ANALYTICAL CHEMISTRY LA English DT Article ID MAGNETIC-RELAXATION; AGGREGATION; SYSTEMS AB Magnetic particles can act as magnetic relaxation switches (MRSVs) when they bind to target analytes, and switch between their dispersed and aggregated states resulting in changes in the spin-spin relaxation time (T(2)) of their surrounding water protons. Both nanoparticles (NPs, 10-100 nm) and micrometer-sized particles (MPs) have been employed as MRSw's, to sense drugs, metabolites, oligonucleotides, proteins, bacteria, and mammalian cells. To better understand how NPs or MPs interact with targets, we employed as a molecular recognition system the reaction between the Tag peptide of the influenza virus hemagglutinin and a monoclonal antibody to that peptide (anti-Tag). To obtain targets of different size and valency, we attached the Tag peptide to BSA (M(w) = 65000 Daltons, diameter = 8 nm) and to Latex spheres (diameter = 900 nm). To obtain magnetic probes of very different sizes, anti-Tag was conjugated to 40 nm NPs and 1 mu m MPs. MP and NP probes reacted with Tag peptide targets in a manner similar to antibody/antigen reactions in solution, exhibiting so-called Prozone effects. MPs detected all types of targets with higher sensitivity than NPs with targets of higher valency being better detected than those of lower valency. The Tag/anti Tag recognition system can be used to synthesize combinations of molecular targets and magnetic probes, to more fully understand the aggregation reaction that occurs when probes bind targets in solution and the ensuing changes in water relaxation times that result. C1 [Koh, Isaac; Hong, Rui; Weissleder, Ralph; Josephson, Lee] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St, Boston, MA 02129 USA. EM ljosephson@mgh.harvard.edu FU NIH [R01-EB0004626, U01-HL080731, P50-CA86355, U54-119349] FX We gratefully acknowledge Jongnam Park for his help in taking TEM images. This work was supported by R01-EB0004626, U01-HL080731, P50-CA86355, and U54-119349 from the NIH. NR 16 TC 51 Z9 53 U1 1 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAY 1 PY 2009 VL 81 IS 9 BP 3618 EP 3622 DI 10.1021/ac802717c PG 5 WC Chemistry, Analytical SC Chemistry GA 439MY UT WOS:000265632400056 PM 19323458 ER PT J AU Baranov, D Bickler, PE Crosby, GJ Culley, DJ Eckenhoff, MF Eckenthoff, RG Hogan, KJ Jevtovic-Todorovic, V Palotas, A Perouansky, M Planel, E Silverstein, JH Wei, HF Whittington, RA Xie, ZC Zuo, ZY AF Baranov, Dmitri Bickler, Philip E. Crosby, Gregory J. Culley, Deborah J. Eckenhoff, Maryellen F. Eckenthoff, Roderic G. Hogan, Kirk J. Jevtovic-Todorovic, Vesna Palotas, Andras Perouansky, Misha Planel, Emmanuel Silverstein, Jeffrey H. Wei, Huafeng Whittington, Robert A. Xie, Zhongcong Zuo, Zhiyi TI Consensus Statement: First International Workshop on Anesthetics and Alzheimer's Disease SO ANESTHESIA AND ANALGESIA LA English DT Article ID POSTOPERATIVE COGNITIVE DYSFUNCTION; ISOFLURANE INDUCES APOPTOSIS; BETA-PROTEIN-LEVELS; NONCARDIAC SURGERY; RAT-BRAIN; ACTIVATION; EXPOSURE; IMPAIRMENT; DEMENTIA; CALCIUM AB In order to review the current status of the potential relationship between anesthesia and Alzheimer's disease, a group of scientists recently met in Philadelphia for a full day of presentations and discussions. This special article represents a consensus view on the possible link between Alzheimer's disease and anesthesia and the steps required to test this more definitively. C1 [Baranov, Dmitri; Eckenhoff, Maryellen F.; Eckenthoff, Roderic G.; Wei, Huafeng] Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Bickler, Philip E.] Univ Calif San Francisco, Dept Anesthesia, Med Ctr, San Francisco, CA 94143 USA. [Crosby, Gregory J.; Culley, Deborah J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA. [Hogan, Kirk J.; Perouansky, Misha] Univ Wisconsin, Dept Anesthesiol, Madison, WI USA. [Jevtovic-Todorovic, Vesna; Zuo, Zhiyi] Univ Virginia Hlth Syst, Dept Anesthesiol, Charlottesville, VA USA. [Palotas, Andras] Asklepios Med Bt, Szeged, Hungary. [Planel, Emmanuel] Columbia Univ, Dept Pathol, Taub Inst Alzheimers Dis Res, Med Ctr, New York, NY USA. [Silverstein, Jeffrey H.] NYU, Dept Anesthesiol, Mt Sinai Sch Med, New York, NY 10016 USA. [Whittington, Robert A.] Columbia Univ, Dept Anesthesiol, Med Ctr, New York, NY USA. [Xie, Zhongcong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Eckenthoff, RG (reprint author), Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, 305 John Morgan,3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM roderic.eckenhoff@uphs.upenn.edu RI Zuo, Zhiyi/F-3950-2010 OI Zuo, Zhiyi/0000-0002-3542-5047 FU NIA NIH HHS [R21 AG029856, R21 AG029856-01A2]; NIGMS NIH HHS [R01 GM088801, K08 GM073224, R01 GM088801-01A1]; NINDS NIH HHS [K08 NS048140, K08 NS048140-04] NR 34 TC 68 Z9 71 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2009 VL 108 IS 5 BP 1627 EP 1630 DI 10.1213/ane.0b013e318199dc72 PG 4 WC Anesthesiology SC Anesthesiology GA 436OA UT WOS:000265422300043 PM 19372347 ER PT J AU Sapru, A Hansen, H Ajayi, T Brown, R Garcia, O Zhuo, HJ Wiemels, J Matthay, MA Wiener-Kronish, J AF Sapru, Anil Hansen, Helen Ajayi, Temitayo Brown, Ron Garcia, Oscar Zhuo, HanJing Wiemels, Joseph Matthay, Michael A. Wiener-Kronish, Jeanine TI 4G/5G Polymorphism of Plasminogen Activator Inhibitor-1 Gene Is Associated with Mortality in Intensive Care Unit Patients with Severe Pneumonia SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 103rd International Conference of the American-Thoracic-Society CY MAY 18-23, 2007 CL San Francisco, CA SP Amer Thorac Soc ID RESPIRATORY-DISTRESS-SYNDROME; COMMUNITY-ACQUIRED PNEUMONIA; UROKINASE RECEPTOR; LOCAL ACTIVATION; FIBRIN TURNOVER; TISSUE FACTOR; LUNG-DISEASE; COAGULATION; GUIDELINES; PROMOTER AB Background: Higher plasma and pulmonary edema fluid levels of plasminogen activator inhibitor-1 (PAI-1) are associated with increased mortality in patients with pneumonia and acute lung injury. The 4G allele of the 4G/5G polymorphism of the PAI-1 gene is associated with higher PAI-1 levels and an increased incidence of hospitalizations for pneumonia. The authors hypothesized that the 4G allele would be associated with worse clinical outcomes (mortality and ventilator-free days) in patients with severe pneumonia. Methods: The authors enrolled patients admitted with severe pneumonia in a prospective cohort. Patients were followed until hospital discharge. DNA was isolated from blood samples, and genotyping detection for the PAI-1 4G/5G polymorphism was carried out using Taqman-based allelic discrimination. Results. A total of Ill patients were available for analysis. Distribution of genotypes was 4G/4G 26 of 111 (23%), 4G/5G 59 of 111 (53%), and 5G/5G 26 of 111 (23%). Of 111 patients, 32 (29%) died before hospital discharge and 105 patients (94%) received mechanical ventilation. Patients with the 4G/4G and the 4G/5G genotypes had higher mortality (35% vs. 8%, P = 0.007) and fewer ventilator-free days (median 4 vs. 13, P = 0.04) compared to patients with the 5G/5G genotype. Conclusions: The 4G allele of the 4G/5G polymorphism in the PAI-1 gene is associated with fewer ventilator-free days and increased mortality in hospitalized patients with severe pneumonia. These findings suggest that PAI-1 may have a role in pathogenesis and that the 4G/5G polymorphism may be an important biomarker of risk in patients with severe pneumonia. C1 [Sapru, Anil] Univ Calif San Francisco, Div Crit Care Med, Dept Pediat, San Francisco, CA 94143 USA. [Brown, Ron; Garcia, Oscar; Zhuo, HanJing; Matthay, Michael A.] Univ Calif San Francisco, Dept Med & Anesthesia, San Francisco, CA 94143 USA. [Hansen, Helen; Wiemels, Joseph] Univ Calif San Francisco, Mol Epidemiol Lab, San Francisco, CA 94143 USA. [Matthay, Michael A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Wiener-Kronish, Jeanine] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Sapru, A (reprint author), Univ Calif San Francisco, Div Crit Care Med, Dept Pediat, Box 0106, San Francisco, CA 94143 USA. EM anil.sapru@ucsf.edu FU NHLBI NIH HHS [K23 HL085526-02, K23 HL085526-01A1, HL074005, K23 HL085526, P50 HL074005, 1 K23 HL085526-01]; NICHD NIH HHS [K12 HD047349, HD047349] NR 33 TC 21 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2009 VL 110 IS 5 BP 1086 EP 1091 PG 6 WC Anesthesiology SC Anesthesiology GA 437QW UT WOS:000265503000021 PM 19387177 ER PT J AU Hamner, MB Faldowski, RA Robert, S Ulmer, HG Horner, MD Lorberbaum, JP AF Hamner, Mark B. Faldowski, Richard A. Robert, Sophie Ulmer, Helen G. Horner, Michael David Lorberbaum, Jeffrey P. TI A preliminary controlled trial of divalproex in posttraumatic stress disorder SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article DE posttraumatic stress disorder; divalproex; anticonvulsant; mood stabilizer; psychopharmacology ID PLACEBO-CONTROLLED TRIAL; SLEEP QUALITY INDEX; OPEN-LABEL; DOUBLE-BLIND; VALPROATE; TOPIRAMATE; TIAGABINE; EFFICACY; SCALE; CARBAMAZEPINE AB BACKGROUND: Case reports and open trials have r ported beneficial effects of divalproex in tire treatment of posttraumatic stress disorder (PTSD). The objective of this study was to conduct a placebo-controlled study of the efficacy and tolerability of divalproex in chronic PTSD patients. METHODS: Patients were randomized to receive placebo or divalproex. T e primary outcome measure was the Clinician Administered PTSD Scale (CAPS). RESULTS: Of 29 patients randomized, 16 received divalproex and 13 placebo. There were no significant differences between groups in mean change from baseline to end point (last observation carried forward) on the CAPS total score or subscales except for a significant decrease in avoidance/numbing scores with placebo. The only significant difference in secondary outcomes was a greater improvement in Clinical Global Impression Scale-Severity favoring placebo. CONCLUSIONS: Divalproex was not superior to placebo in this study. This could be due to lack of efficacy of divalproex in this population, inadequate sample size to detect differences, or other factors. Further study of divalproex is needed to better clarify the role of this agent in PTSD. C1 [Hamner, Mark B.; Robert, Sophie; Ulmer, Helen G.; Horner, Michael David] Med Univ S Carolina, Dept Psychiat, Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC 29425 USA. [Lorberbaum, Jeffrey P.] Penn State Univ, Milton S Hershey Med Ctr, Dept Psychiat, Hershey, PA 17033 USA. RP Hamner, MB (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM hamnermb@musc.edu FU Abbott Laboratories (investigator-initiated protocol) FX This study was funded by Abbott Laboratories (investigator-initiated protocol) and was conducted at the Ralph H. Johnson VA Medical Center, Charleston, SC. The results were presented in part at the 44th Annual New Clinical Drug Evaluation Unit, June 1-4, 2004; Phoenix, AZ. We are grateful to Charlotte Teneback, MD, Jennifer Mixson, RPh, and Deborah Agbor-Tabi, MPH, for their technical support, and to the veterans who participated in this study. NR 45 TC 19 Z9 19 U1 3 U2 6 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 1040-1237 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD MAY PY 2009 VL 21 IS 2 BP 89 EP 94 PG 6 WC Psychiatry SC Psychiatry GA 496NH UT WOS:000269980700005 PM 19439158 ER PT J AU Gordon, JA AF Gordon, James A. TI Social Welfare in the Hospital Emergency Department: The Challenge of Integrated Community Health Care SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material C1 [Gordon, James A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Gordon, James A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA. [Gordon, James A.] Harvard Univ, Div Emergency Med, Sch Med, Boston, MA 02114 USA. RP Gordon, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, 0 Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM jgordon3@partners.org NR 11 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAY PY 2009 VL 53 IS 5 BP 603 EP 604 DI 10.1016/j.annemergmed.2008.12.017 PG 2 WC Emergency Medicine SC Emergency Medicine GA 441YO UT WOS:000265806700010 PM 19181421 ER PT J AU Gschwendtner, A Bevan, S Cole, JW Plourde, A Matarin, M Ross-Adams, H Meitinger, T Wichmann, E Mitchell, BD Furie, K Slowik, A Rich, SS Syme, PD MacLeod, MJ Meschia, JF Rosand, J Kittner, SJ Markus, HS Muller-Myhsok, B Dichgans, M AF Gschwendtner, Andreas Bevan, Steve Cole, John W. Plourde, Anna Matarin, Mar Ross-Adams, Helen Meitinger, Thomas Wichmann, Erich Mitchell, Braxton D. Furie, Karen Slowik, Agnieszka Rich, Stephen S. Syme, Paul D. MacLeod, Mary J. Meschia, James F. Rosand, Jonathan Kittner, Steve J. Markus, Hugh S. Mueller-Myhsok, Bertram Dichgans, Martin CA Int Stroke Genetics Consortium TI Sequence Variants on Chromosome 9p21.3 Confer Risk for Atherosclerotic Stroke SO ANNALS OF NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; TRANSIENT ISCHEMIC ATTACK; SMOOTH-MUSCLE-CELLS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; PLAQUE VULNERABILITY; MEDIA THICKNESS; METAANALYSIS; REPLICATION AB Objective: Recent studies have identified a major locus for risk for coronary artery disease and myocardial infiarction on chromosome 9p21.3. Stroke, in particular, ischemic stroke caused by atherosclerotic disease, shares common mechanisms with myocardial infarction. We investigated whether the 9p21 region contributes to ischemic stroke risk. Methods: In an initial screen, 15 single nucleotide polymorphisms (SNPs) covering the critical genetic interval on 9p21 were genotyped in samples from Southern Germany (1,090 cases, 1,244 control subjects) and the United Kingdom (758 cases, 872 control subjects, 3 SNPs). SNPs significantly associated with ischemic stroke or individual stroke subtypes in either of the screening samples were Subsequently genotyped in 2,528 additional cases and 2,189 additional control Subjects from Europe and North America. Results: Genotyping of the screening samples demonstrated associations between seven SNPs and atherosclerotic stroke (all p < 0.05). Analysis of the full sample confirmed associations between six SNPs and atherosclerotic stroke in multivariate analyses controlling for demographic variables, coronary, artery disease, myocardial infarction, and vascular risk factors (all p < 0.05). The odds ratios for the lead SNP (rs1537378-C) were similar in the various subsamples with a pooled odds ratio of 1.21 (95% confidence interval, 1.07-1.37) under both fixed- and random-effects models (p = 0.002). The point estimate for the population attributable risk is 20.1% For atherosclerotic stroke. Interpretation: The chromosome 9p21.3 region represents a major risk locus for atherosclerotic stroke. The effect of this locus on stroke appears to be independent of its relation to coronary artery disease and other stroke risk factors. Our findings support a broad role of the 9p21 region in arterial disease. C1 [Gschwendtner, Andreas; Dichgans, Martin] Univ Munich, Klinikum Grosshadern, Dept Neurol, Munich, Germany. [Bevan, Steve; Markus, Hugh S.] Univ London, Ctr Clin Neurosci, London, England. [Cole, John W.; Mitchell, Braxton D.; Kittner, Steve J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Cole, John W.; Mitchell, Braxton D.; Kittner, Steve J.] Vet Affairs Med Ctr, Baltimore, MD USA. [Plourde, Anna; Furie, Karen; Rosand, Jonathan] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. [Plourde, Anna; Furie, Karen; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Matarin, Mar] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Ross-Adams, Helen; MacLeod, Mary J.] Univ Aberdeen, Dept Med & Therapeut, Aberdeen, Scotland. [Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, Munich, Germany. [Wichmann, Erich] Helmholtz Zentrum Munchen, Inst Epidemiol, Munich, Germany. [Wichmann, Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Syme, Paul D.] Univ Edinburgh, Dept Clin & Surg Sci, Edinburgh, Midlothian, Scotland. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany. RP Dichgans, M (reprint author), Marchioninistr 15, D-81377 Munich, Germany. EM martin.dichgans@med.uni-muenchen.de RI Muller-Myhsok, Bertram/A-3289-2013; Meitinger, Thomas/O-1318-2015; Matarin, Mar/F-1771-2016; OI Matarin, Mar/0000-0002-4717-5735; Bevan, Steve/0000-0003-0490-6830; Mitchell, Braxton/0000-0003-4920-4744; Macleod, Mary Joan/0000-0003-2115-8184 FU Chief Scientist Office [CZG/4/1/26]; NIDDK NIH HHS [P30 DK072488, P30 DK079637]; NINDS NIH HHS [K23 NS 042720, K23 NS042720-01, K23 NS042720-02, K23 NS042720-03, K23 NS042720-04, K23 NS042720-05, P50 NS 051343, P50 NS051343-01A2, R01 NS 42733, R01 NS042733, R01 NS042733-01, R01 NS042733-02, R01 NS042733-03, R01 NS042733-04, R01 NS042733-05, R01 NS045012, R01 NS045012-05] NR 38 TC 127 Z9 129 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2009 VL 65 IS 5 BP 531 EP 539 DI 10.1002/ana.21590 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 453LJ UT WOS:000266611700009 PM 19475673 ER PT J AU Gelber, RD AF Gelber, R. D. TI DESIGNING CLINICAL TRIALS TO GUIDE TREATMENT FOR INDIVIDUAL PATIENTS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT IMPAKT Breast Cancer Conference 2009 CY MAY 07-09, 2009 CL Brussels, BELGIUM SP GlaxoSmithKline, IPSOGEN, ROCHE, AMGEN, Merck Seromo, Genom, Pfizer Oncol, Bristol Myers Squibb, Onyx, Schering-Plough, Wyeth C1 [Gelber, R. D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 11 EP 11 PG 1 WC Oncology SC Oncology GA 451VC UT WOS:000266498000005 ER PT J AU Garber, JE AF Garber, J. E. TI TEACHING AN OLD DOG NEW TRICKS: ALKYLATING AGENTS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT IMPAKT Breast Cancer Conference 2009 CY MAY 07-09, 2009 CL Brussels, BELGIUM SP GlaxoSmithKline, IPSOGEN, ROCHE, AMGEN, Merck Seromo, Genom, Pfizer Oncol, Bristol Myers Squibb, Onyx, Schering-Plough, Wyeth C1 [Garber, J. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 18 EP 18 PG 1 WC Oncology SC Oncology GA 451VC UT WOS:000266498000028 ER PT J AU Polyak, K AF Polyak, K. TI THERAPEUTIC TARGETING OF TUMOR CELL DIVERSITY SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT IMPAKT Breast Cancer Conference 2009 CY MAY 07-09, 2009 CL Brussels, BELGIUM SP GlaxoSmithKline, IPSOGEN, ROCHE, AMGEN, Merck Seromo, Genom, Pfizer Oncol, Bristol Myers Squibb, Onyx, Schering-Plough, Wyeth C1 [Polyak, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 19 EP 19 PG 1 WC Oncology SC Oncology GA 451VC UT WOS:000266498000030 ER PT J AU Griffin, J AF Griffin, J. TI THE FLT3 TYROSINE KINASE AS A THERAPEUTIC TARGET IN ACUTE MYELOBLASTIC LEUKEMIA SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 7th International Symposium on Targeted Anticancer Therapies CY MAR 23-25, 2009 CL Amsterdam, NETHERLANDS C1 [Griffin, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 23 EP 23 PG 1 WC Oncology SC Oncology GA 451VD UT WOS:000266498100031 ER PT J AU Paridaens, R Badwe, R Sun, Y Dirix, L Cardoso, F Powell, C Zacharchuk, C Burstein, HJ AF Paridaens, R. Badwe, R. Sun, Y. Dirix, L. Cardoso, F. Powell, C. Zacharchuk, C. Burstein, H. J. TI NERATINIB (HKI-272), AN IRREVERSIBLE PAN ERBB RECEPTOR TYROSINE KINASE INHIBITOR: PHASE 2 RESULTS IN PATIENTS WITH ERBB2+ADVANCED BREAST CANCER SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT IMPAKT Breast Cancer Conference 2009 CY MAY 07-09, 2009 CL Brussels, BELGIUM SP GlaxoSmithKline, IPSOGEN, ROCHE, AMGEN, Merck Seromo, Genom, Pfizer Oncol, Bristol Myers Squibb, Onyx, Schering-Plough, Wyeth C1 [Paridaens, R.] Univ Hosp Gasthuisberg Katholieke, Leuven, Belgium. [Badwe, R.] Tata Mem Hosp, Dept Surg Oncol, Mumbai 400012, Maharashtra, India. [Sun, Y.] Chinese Acad Med Sci, Beijing 100037, Peoples R China. [Dirix, L.] AZ St Augustinus, Oncol, Antwerp, Belgium. [Cardoso, F.] Inst Jules Bordet, Med Oncol & Translat Res Unit, B-1000 Brussels, Belgium. [Powell, C.] Wyeth Ayerst Res, Biostat, Cambridge, MA USA. [Zacharchuk, C.] Wyeth Ayerst Res, Oncol, Cambridge, MA USA. [Burstein, H. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 61 EP 61 PG 1 WC Oncology SC Oncology GA 451VC UT WOS:000266498000182 ER PT J AU Michaelson, MD Regan, MM Oh, WK Kaufman, DS Olivier, K Michaelson, SZ Spicer, B Gurski, C Kantoff, PW Smith, MR AF Michaelson, M. Dror Regan, M. M. Oh, W. K. Kaufman, D. S. Olivier, K. Michaelson, S. Z. Spicer, B. Gurski, C. Kantoff, P. W. Smith, M. R. TI Phase II study of sunitinib in men with advanced prostate cancer SO ANNALS OF ONCOLOGY LA English DT Article DE angiogenesis; castration; docetaxel; PSA; resistant ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; FACTOR-RECEPTOR; RADICAL PROSTATECTOMY; CLINICAL-TRIALS; WORKING GROUP; B CHAINS; IN-VIVO; SORAFENIB; DOCETAXEL AB Background: This study explored the efficacy and tolerability of sunitinib, an inhibitor of tyrosine kinase receptors, in men with castration-resistant prostate cancer (CRPC). Methods: Men with no prior chemotherapy (group A) and men with docetaxel (Taxotere)-resistant prostate cancer (group B) were treated with sunitinib. The primary end point was confirmed 50% prostate-specific antigen (PSA) decline. Secondary end points included objective response rate and safety. Serum-soluble biomarkers were measured. Results: Seventeen men were enrolled in each group. One confirmed PSA response was observed in each group, and an additional eight men and seven men had stable PSA at week 12 in groups A and B, respectively. Improvements in imaging were observed in the absence of post-treatment PSA declines. Common adverse effects included fatigue, nausea, diarrhea, myelosuppression and transaminase elevation. Significant changes following sunitinib treatment were observed in serum-soluble biomarkers including soluble vascular endothelial growth factor receptor-2, platelet-derived growth factor aa, placental growth factor and leptin. Conclusions: Sunitinib monotherapy resulted in few confirmed 50% post-treatment declines in PSA in men with CRPC. Serum markers of angiogenesis confirmed on-target effects of sunitinib. Assessments of radiographic disease status were often discordant with changes in PSA, indicating that alternate end points are important in future trials. C1 [Michaelson, M. Dror; Kaufman, D. S.; Olivier, K.; Michaelson, S. Z.; Spicer, B.; Gurski, C.; Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. [Regan, M. M.; Oh, W. K.; Kantoff, P. W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Michaelson, M. Dror; Oh, W. K.; Kaufman, D. S.; Kantoff, P. W.; Smith, M. R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Regan, M. M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM dmichaelson1@partners.org RI Oh, William/B-9163-2012; OI Oh, William/0000-0001-5113-8147; Michaelson, Dror/0000-0001-9249-6338 FU Department of Defense Prostate Cancer Research Program Clinical Trial Award [PC-050010]; NIH K24 Midcareer Investigator Award [5K24CA121990-02]; Prostate Cancer Foundation FX Department of Defense Prostate Cancer Research Program Clinical Trial Award number (PC-050010) to MDM; NIH K24 Midcareer Investigator Award (5K24CA121990-02) and Prostate Cancer Foundation to MRS. NR 32 TC 92 Z9 93 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 IS 5 BP 913 EP 920 DI 10.1093/annonc/mdp111 PG 8 WC Oncology SC Oncology GA 440ZY UT WOS:000265739700018 ER PT J AU Posner, MR Norris, CM Wirth, LJ Shin, DM Cullen, KJ Winquist, EW Blajman, CR Mickiewicz, EA Frenette, GP Plinar, LF Cohen, RB Steinbrenner, LM Freue, JM Gorbunova, VA Tjulandin, SA Raez, LE Adkins, DR Tishler, RB Roessner, MR Haddad, RI AF Posner, M. R. Norris, C. M. Wirth, L. J. Shin, D. M. Cullen, K. J. Winquist, E. W. Blajman, C. R. Mickiewicz, E. A. Frenette, G. P. Plinar, L. F. Cohen, R. B. Steinbrenner, L. M. Freue, J. M. Gorbunova, V. A. Tjulandin, S. A. Raez, L. E. Adkins, D. R. Tishler, R. B. Roessner, M. R. Haddad, R. I. CA TAX 324 Study Grp TI Sequential therapy for the locally advanced larynx and hypopharynx cancer subgroup in TAX 324: survival, surgery, and organ preservation SO ANNALS OF ONCOLOGY LA English DT Article DE chemotherapy; chemoradiotherapy; head and neck cancer; larynx cancer; hypopharynx cancer; organ preservation ID PHASE-III TRIAL; NECK-CANCER; NEOADJUVANT CHEMOTHERAPY; ADVANCED HEAD; CONCURRENT CHEMOTHERAPY; CISPLATIN; FLUOROURACIL; CARCINOMA; RADIATION; DOCETAXEL AB Background: Locally advanced laryngeal and hypopharyngeal cancers (LHC) represent a group of cancers for which surgery, laryngectomy-free survival (LFS), overall survival (OS), and progression-free survival (PFS) are clinically meaningful end points. Patients and methods: These outcomes were analyzed in the subgroup of assessable LHC patients enrolled in TAX 324, a phase III trial of sequential therapy comparing docetaxel plus cisplatin and fluorouracil (TPF) against cisplatin and fluorouracil (PF), followed by chemoradiotherapy. Results: Among 501 patients enrolled in TAX 324, 166 had LHC (TPF, n = 90; PF, n = 76). Patient characteristics were similar between subgroups. Median OS for TPF was 59 months [95% confidence interval (CI): 31-not reached] versus 24 months (95% CI: 13-42) for PF [hazard ratio (HR) for death: 0.62; 95% CI: 0.41-0.94; P = 0.024]. Median PFS for TPF was 21 months (95% CI: 12-59) versus 11 months (95% CI: 8-14) for PF (HR: 0.66; 95% CI: 0.45-0.97; P = 0.032). Among operable patients (TPF, n = 67; PF, n = 56), LFS was significantly greater with TPF (HR: 0.59; 95% CI: 0.37-0.95; P = 0.030). Three-year LFS with TPF was 52% versus 32% for PF. Fewer TPF patients had surgery (22% versus 42%; P = 0.030). Conclusions: In locally advanced LHC, sequential therapy with induction TPF significantly improved survival and PFS versus PF. Among operable patients, TPF also significantly improved LFS and PFS. These results support the use of sequential TPF followed by carboplatin chemoradiotherapy as a treatment option for organ preservation or to improve survival in locally advanced LHC. C1 [Posner, M. R.; Wirth, L. J.; Haddad, R. I.] Harvard Univ, Sch Med, Div Adult Oncol, Dana Farber Canc Inst,Brigham & Womens Hosp, Boston, MA 02115 USA. [Norris, C. M.] Harvard Univ, Sch Med, Dept Surg Oncol, Dana Farber Canc Inst,Brigham & Womens Hosp, Boston, MA 02115 USA. [Norris, C. M.] Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst,Brigham & Womens Hosp, Boston, MA 02115 USA. [Shin, D. M.] Univ Pittsburgh, Dept Hematol & Med Oncol, Sch Med, Pittsburgh, PA 15260 USA. [Cullen, K. J.] Georgetown Univ, Sch Med, Dept Med Oncol, Washington, DC USA. [Winquist, E. W.] London Reg Canc Ctr, Dept Oncol, London, ON N6A 4L6, Canada. [Blajman, C. R.] Hosp JB Iturraspe, Serv Oncol Clin, Santa Fe, NM USA. [Mickiewicz, E. A.] Inst Angel H Roffo, Dept Oncol, Buenos Aires, DF, Argentina. [Frenette, G. P.] Blumenthal Canc Ctr, Charlotte, NC USA. [Plinar, L. F.] Univ Med & Dent New Jersey, Div Hematol & Oncol, Newark, NJ 07103 USA. [Cohen, R. B.] Univ Virginia, Div Hematol Oncol, Charlottesville, VA USA. [Steinbrenner, L. M.] VA Western NY Hlth Care Syst, Dept Hematol Oncol, Buffalo, NY USA. [Freue, J. M.] Hosp Evita, Buenos Aires, DF, Argentina. [Tjulandin, S. A.] Russian Canc Res Ctr, Dept Clin Pharmacol & Chemotherapy, Moscow, Russia. [Raez, L. E.] Sylvester Canc Ctr, Dept Med, Miami, FL USA. [Adkins, D. R.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Tishler, R. B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Roessner, M. R.] Sanofi Aventis, Biostat, Bridgewater, MA USA. RP Posner, MR (reprint author), Harvard Univ, Sch Med, Div Adult Oncol, Dana Farber Canc Inst,Brigham & Womens Hosp, 44 Binney St,SW430, Boston, MA 02115 USA. EM marshall_posner@dfci.harvard.edu RI Ray, Dana/C-3470-2013; Shin, Dong Moon/G-9649-2013 FU Sanofi-aventis FX Sanofi-aventis. NR 20 TC 62 Z9 63 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 IS 5 BP 921 EP 927 DI 10.1093/annonc/mdn752 PG 7 WC Oncology SC Oncology GA 440ZY UT WOS:000265739700019 PM 19179556 ER PT J AU Lahav, Y Burns, JA Feinberg, S Heaton, JT Zeitels, SM AF Lahav, Yonatan Burns, James A. Feinberg, Steven Heaton, James T. Zeitels, Steven M. TI Initial Anatomic Geographic Presentation of Glottal Dysplasia SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE dysplasia; hoarseness; keratosis; premalignant mucosa; vocal cord; vocal fold ID KERATOSIS; LARYNX; PAPILLOMATOSIS; HYPERPLASIA; CARCINOMA; LASER AB Glottal dysplasia is likely the most common laryngeal disease with a discernible lesion; however, investigations describing its initial anatomic geographic presentation are rare. To examine this, we identified 52 patients who did not have significant prior treatment or glottal cancer. Thirty-one patients had bilateral disease, so there were 83 vocal folds with precancerous dysplasia. The phonatory mucosa was the dominant disease site ill all; the epicenter was on the superior surface in 65 of the 83 folds and on the medial surface in 18 of the 83 folds. The arytenoid mucosa was involved in 8 of the 83 folds. Nineteen of the 52 patients had direct anterior-commissure involvement, and none had interarytenoid mucosal disease. The investigation established the commonly held principle that glottal dysplasia occurs primarily on phonatory mucosa. Given the frequent occurrence and recurrence of glottal dysplasia, treatment goals should focus on disease control to prevent malignant degeneration while preserving the subepithelial superficial lamina propria, necessary for phonatory mucosal pliability, vocal fold vibration, and optimal vocal function. C1 Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. NR 16 TC 2 Z9 2 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAY PY 2009 VL 118 IS 5 BP 321 EP 325 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 445WW UT WOS:000266083200001 PM 19548379 ER PT J AU Del Vecchio, D AF Del Vecchio, Daniel TI Breast Reconstruction for Breast Asymmetry Using Recipient Site Pre-Expansion and Autologous Fat Grafting SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Northeastern-Society-of-Plastic-Surgeons CY OCT 02-05, 2008 CL Philadelphia, PA SP NE Soc Plast Surg ID HARVEST; CELLS AB A single case is reported utilizing, recipient site pre-expansion With BRAVA (Brava, Inc, Miami, FL) followed by autologous fat grafting to the breast in a patient with severe breast asymmetry, Recipient site preexpansion, used 2 to 3 weeks before fat grafting and 2 weeks after fat grafting may have both practical and theoretical benefits in optimizing the volume and enhancing the survival of grafted adipocytes, the mechanism of which is discussed. Recipient site pre-expansion and fat grafting may have early clinical adoption in cases of severe asymmetry, tuberous breasts, and other deformities that are difficult to treat with current reconstructive techniques, but studies are needed to clearly delineate its safety and its role. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Del Vecchio, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dandelvecchio@aol.com NR 14 TC 26 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAY PY 2009 VL 62 IS 5 BP 523 EP 527 DI 10.1097/SAP.0b013e3181a23f08 PG 5 WC Surgery SC Surgery GA 437AY UT WOS:000265459200016 PM 19387154 ER PT J AU Yueh, JH Houlihan, MJ Slavin, SA Lee, BT Pories, SE Morris, DJ AF Yueh, Janet H. Houlihan, Mary Jane Slavin, Sumner A. Lee, Bernard T. Pories, Susan E. Morris, Donald J. TI Nipple-Sparing Mastectomy Evaluation of Patient Satisfaction, Aesthetic Results, and Sensation SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Northeastern-Society-of-Plastic-Surgeons CY OCT 02-05, 2008 CL Philadelphia, PA SP NE Soc Plast Surg DE nipple-sparing mastectomy; breast reconstruction; breast cancer; patient satisfaction; nipple sensation; decision-making process ID IMMEDIATE BREAST RECONSTRUCTION; CANCER; RISK; CONSERVATION; INVOLVEMENT; RECURRENCE AB The purpose of this study is to describe our experience with nipple-sparing mastectomy and immediate reconstruction, with particular attention to patient satisfaction. aesthetic results. and nipple sensation. Immediate reconstruction was performed on 17 breasts in 10 patients, using either implants or autologous tissue flaps. Assessment of outcomes was performed through patient interviews, a self-reported patient satisfaction survey and review of postoperative photographs. Short-term complications included partial loss of the nipple-areolar complex requiring debridement (n = 3) and removal of the nipple-areolar complex (n = 2) for occult ductal carcinoma in situ. While all patients with completed breast reconstructions were satisfied with their general reconstructive experience, 6 of 9 patients were aesthetically satisfied with their breast reconstruction. Postoperative nipple Sensation was reported in 75% of patients, although sensation was low (mean of 2.8 of 10). As nipple-sparing mastectomy is becoming an increasing patient preference. preoperative discussion needs to address expectations, aesthetic satisfaction, and long-term cancer control. C1 [Houlihan, Mary Jane; Pories, Susan E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Breast Surg, Boston, MA 02215 USA. [Yueh, Janet H.; Slavin, Sumner A.; Lee, Bernard T.; Morris, Donald J.] Harvard Univ, Sch Med, Div Plast & Reconstruct Surg, Boston, MA 02215 USA. RP Houlihan, MJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Breast Surg, Shapiro Bldg Breast Ctr CC-5,330 Brookline Ave, Boston, MA 02215 USA. EM mhouliha@bidmc.harvard.edu RI Lee, Bernard/K-1106-2016 OI Lee, Bernard/0000-0002-5533-3166 NR 25 TC 41 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 EI 1536-3708 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAY PY 2009 VL 62 IS 5 BP 586 EP 590 DI 10.1097/SAP.0b013e31819fb1ac PG 5 WC Surgery SC Surgery GA 437AY UT WOS:000265459200029 PM 19387167 ER PT J AU Zhong, T Antony, A Cordeiro, P AF Zhong, Toni Antony, Anu Cordeiro, Peter TI Surgical Outcomes and Nipple Projection Using the Modified Skate Flap for Nipple-Areolar Reconstruction in a Series of 422 Implant Reconstructions SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Northeastern-Society-of-Plastic-Surgeons CY OCT 02-05, 2008 CL Philadelphia, PA SP NE Soc Plast Surg DE breast reconstruction; implant; tissue expander; nipple areolar reconstruction; long-term nipple projection; modified skate flap; technique; surgical outcome ID DOUBLE-OPPOSING-TAB; TISSUE; SKIN AB Numerous techniques have been used in an attempt to achieve long-term nipple projection following nipple-areolar reconstruction (NAR). A common setback, however, is the diminution of projection over time; this phenomenon is particularly evident following implant based breast reconstruction. The purpose of this report was thus to evaluate surgical outcomes and long-term nipple projection with the use of "modified skate flap" technique in exclusively implant based postmastectomy reconstructions. A retrospective review was performed for the period between 1993 and 2007. All consecutive patients with 2-staged tissue expander/implant reconstructions followed by NAR using the modified skate flap technique performed by the senior author (P.C.) were identified in a prospectively maintained breast reconstruction database. Only patients with a minimum of 1-year follow-up were included in the study. Patients with a history of irradiation to the breast were excluded from nipple projection assessment. Clinical outcome measurements included long-term nipple projection as well as incidence of complications from the NAR procedure using the modified skate flap technique. Over the 15-year study period, 475 patients underwent 2-staged tissue expander/implant reconstruction followed by NAR using the modified skate flap technique. Of these, there was a total of 292 patients with the minimum requirement of 1-year follow-up post NAR (61% follow-up rate). The total number of reconstructed nipple areolar complexes evaluated in this series was 422 (130 bilateral and 162 unilateral NAR). Forty patients (28 unilateral and 12 bilateral NAR) who received radiation to their breasts were excluded from nipple projection assessment. At a median follow-up of 44 months (range: 12-84 months), mean nipple projection was 2.5 mm (range: 1-4 mm). Minor complications occurred in 7.2% of the patients (n = 292). Skin graft donor site dehiscence was the most common complication (3.1%) followed by partial skin graft nontake of the areola (2.1%). This report documents the largest series of NAR using a single technique in the setting of postmastectomy reconstructions. This technique can be safely performed over breast implants with acceptably low rates of complications and predictable results. Long-term nipple projection over implant reconstructions using this technique is modest and this must be forewarned to patients completing the final stage of their implant reconstruction. C1 [Cordeiro, Peter] Mem Sloan Kettering Canc Ctr, Dept Surg, Plast & Reconstruct Serv, New York, NY 10021 USA. [Zhong, Toni] Univ Toronto, Univ Hlth Network, Dept Surg, Div Plast & Reconstruct Surg,Breast Restorat Prog, Toronto, ON, Canada. [Antony, Anu] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Cordeiro, P (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Plast & Reconstruct Serv, 1275 York Ave,Room C-1193, New York, NY 10021 USA. NR 25 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAY PY 2009 VL 62 IS 5 BP 591 EP 595 DI 10.1097/SAP.0b013e31819fb1c9 PG 5 WC Surgery SC Surgery GA 437AY UT WOS:000265459200030 PM 19387168 ER PT J AU Hutter, MM AF Hutter, Matthew M. TI Specialization The Answer or the Problem? SO ANNALS OF SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Gen & Gastrointestinal Surg, 15 Parkman St,Wang ACC 335, Boston, MA 02114 USA. EM mhutter@partners.org NR 4 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2009 VL 249 IS 5 BP 717 EP 718 DI 10.1097/01.sla.0000348651.75237.df PG 2 WC Surgery SC Surgery GA 441HR UT WOS:000265760400005 PM 19387302 ER PT J AU Kerfoot, BP Kearney, MC Connelly, D Ritchey, ML AF Kerfoot, B. Price Kearney, Michael C. Connelly, Donna Ritchey, Michael L. TI Interactive Spaced Education to Assess and Improve Knowledge of Clinical Practice Guidelines A Randomized Controlled Trial SO ANNALS OF SURGERY LA English DT Article ID MEDICAL-STUDENTS; SPACING REPETITIONS; RETENTION; RETRIEVAL; UROLOGY; MEMORY; ADULTS; RESIDENTS; INTERVAL; TEACH AB Objective: To determine whether Interactive Spaced Education (ISE) is an effective and acceptable form of graduate and continuing medical education (GME/CME), using clinical practice guideline (CPG) education as an experimental system. Summary Background Data: ISE is a novel form of online education, which combines the pedagogical merits of the spacing and testing effects. Its efficacy for GME and CME is not known. Methods: One-hundred sixty urologists and 320 urology residents were randomized to 1 of 2 cohorts. We developed and validated 48 ISE items (questions and answers) on 5 urology CPGs (hematuria and priapism [HP]; staghorn calculi, infertility, and antibiotic use [SIA]). Physicians were sent 3 emails a week, each containing 2 questions. Content was repeated 3 times over 20 weeks. Cohort A physicians received the 3-cycle ISE course on HP, with 24 control items on SIA in cycle 3. Cohort B physicians received the 3-cycle ISE course on SIA, with 24 control items on HP in cycle 3. Results: The ISE program was completed by 71% urologists and 83% residents. Cohort A scores on HP increased from mean 44.9% in cycle 1% to 75.7% in cycle 3, a 57% relative increase compared with controls (P < 0.001; Cohen effect size, 2.2). Similarly, cohort B scores on SIA increased from 45.2% in cycle 1% to 69.5% in cycle 3, a 56% relative increase compared with controls (P < 0.001; effect size, 2.2). Eighty-four percent of all participants requested to enroll in further ISE programs. Conclusions: ISE is an effective and well-accepted form of GME and CME and is a promising new methodology to improve CPG knowledge. C1 [Kerfoot, B. Price] VA Boston Healthcare Syst, Surg Serv Urol, Jamaica Plain, MA 02130 USA. [Kerfoot, B. Price; Kearney, Michael C.] Harvard Univ, Sch Med, Boston, MA USA. [Kearney, Michael C.] Beth Israel Deaconess Med Ctr, Dept Urol Surg, Boston, MA 02215 USA. [Connelly, Donna] AUA, Linthicum, MD USA. [Ritchey, Michael L.] Mayo Clin, Dept Urol, Phoenix, AZ USA. RP Kerfoot, BP (reprint author), VA Boston Healthcare Syst, Surg Serv Urol, 150 S Huntington Ave,151DIA, Jamaica Plain, MA 02130 USA. EM price.kerfoot@gmail.com FU Research Career Development Award Program of the Veterans Affairs Health Services Research & Development Service; American Urological Association (Linthicum, MD); United States Agency for Healthcare Research and Quality; American Urological Association Foundation (Linthicum, MD); Astellas Pharma US, Inc. FX Supported in part by the Research Career Development Award Program of the Veterans Affairs Health Services Research & Development Service, American Urological Association (Linthicum, MD), the United States Agency for Healthcare Research and Quality, the American Urological Association Foundation (Linthicum, MD), and Astellas Pharma US, Inc. NR 23 TC 32 Z9 33 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2009 VL 249 IS 5 BP 744 EP 749 DI 10.1097/SLA.0b013e31819f6db8 PG 6 WC Surgery SC Surgery GA 441HR UT WOS:000265760400011 PM 19387336 ER PT J AU Puli, SR Reddy, JBK Bechtold, ML Choudhary, A Antillon, MR Brugge, WR AF Puli, Srinivas R. Reddy, Jyotsna B. K. Bechtold, Matthew L. Choudhary, Abhishek Antillon, Mainor R. Brugge, William R. TI Accuracy of Endoscopic Ultrasound to Diagnose Nodal Invasion by Rectal Cancers: A Meta-Analysis and Systematic Review SO ANNALS OF SURGICAL ONCOLOGY LA English DT Review ID FINE-NEEDLE-ASPIRATION; ENDORECTAL ULTRASONOGRAPHY; COMPUTED-TOMOGRAPHY; COLORECTAL-CANCER; TRANSRECTAL ULTRASONOGRAPHY; PREOPERATIVE IRRADIATION; ENDOLUMINAL ULTRASONOGRAPHY; PELVIC EXENTERATION; CONTINUOUS-INFUSION; CARCINOMA AB Nodal staging in patients with rectal cancer predicts prognosis and directs therapy. Published data on the accuracy of endoscopic ultrasound (EUS) for diagnosing nodal invasion in patients with rectal cancer has been inconsistent. To evaluate the accuracy of EUS in diagnosing nodal metastasis of rectal cancers. Study Selection Criteria: Only EUS studies confirmed by surgical histology were selected. Data Collection and Extraction: Articles were searched in Medline, Pubmed, and CENTRAL. Statistical Method: Pooling was conducted by both fixed-effects model and random-effects model. The initial search identified 3610 reference articles in which 352 relevant articles were selected and reviewed. Data were extracted from 35 studies (N = 2732) that met the inclusion criteria. Pooled sensitivity of EUS in diagnosing nodal involvement by rectal cancers was 73.2% (95% confidence interval [95% CI] 70.6-75.6). EUS had a pooled specificity of 75.8% (95% CI 73.5-78.0). The positive likelihood ratio of EUS was 2.84 (95% CI 2.16-3.72), and negative likelihood ratio was 0.42 (95% CI 0.33-0.52). All the pooled estimates, calculated by fixed- and random-effect models, were similar. SROC curves showed an area under the curve of 0.79. The P for chi-squared heterogeneity for all the pooled accuracy estimates was >.10. EUS is an important and accurate diagnostic tool for evaluating nodal metastasis of rectal cancers. This meta-analysis shows that the sensitivity and specificity of EUS is moderate. Further refinement in EUS technologies and diagnostic criteria are needed to improve the diagnostic accuracy. C1 [Puli, Srinivas R.; Reddy, Jyotsna B. K.; Bechtold, Matthew L.; Choudhary, Abhishek; Antillon, Mainor R.] Univ Missouri, Div Gastroenterol & Hepatol, Columbia, MO 65211 USA. [Brugge, William R.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Puli, SR (reprint author), Univ Missouri, Div Gastroenterol & Hepatol, Columbia, MO 65211 USA. EM srinivaspuli@yahoo.com NR 79 TC 68 Z9 74 U1 2 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2009 VL 16 IS 5 BP 1255 EP 1265 DI 10.1245/s10434-009-0337-4 PG 11 WC Oncology; Surgery SC Oncology; Surgery GA 428VG UT WOS:000264878900029 PM 19219506 ER PT J AU Maduekwe, UN Hornicek, FJ Springfield, DS Raskin, KA Harmon, DC Choy, E Rosenberg, AE Nielsen, GP DeLaney, TF Chen, YL Ott, MJ Yoon, SS AF Maduekwe, Ugwuji N. Hornicek, Francis J. Springfield, Dempsey S. Raskin, Kevin A. Harmon, David C. Choy, Edwin Rosenberg, Andrew E. Nielsen, G. Petur DeLaney, Thomas F. Chen, Yen-Lin Ott, Mark J. Yoon, Sam S. TI Role of Sentinel Lymph Node Biopsy in the Staging of Synovial, Epithelioid, and Clear Cell Sarcomas SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID SOFT-TISSUE SARCOMA; POSITRON-EMISSION-TOMOGRAPHY; BREAST-CANCER; MALIGNANT-MELANOMA; THERAPEUTIC UTILITY; SINGLE INSTITUTION; FOLLOW-UP; MICROMETASTASES; METASTASIS; PARTS AB Soft tissue sarcomas generally have a a parts per thousand currency sign5% risk of lymph node metastasis, but synovial, epithelioid, and clear cell subtypes reportedly have a much higher risk. The utility of sentinel lymph node biopsy (SLNB) for patients with these sarcoma subtypes is unknown. 29 patients with nonmetastatic synovial, epithelioid, and clear cell sarcomas who underwent SLNB were examined. Median age was 35 years (range 11-73 years), and 69% were male. Tumors were located in the lower extremity in 17 patients and the upper extremity in 12. The histological subtypes were synovial sarcoma in 16 patients, epithelioid sarcoma in 10, and clear cell sarcoma in 3. All patients had a staging chest computed tomography (CT) scan, none of which were suspicious, and 20 patients had staging positron emission tomography (PET) scans (16 negative, 3 indeterminate, and 1 suspicious). All patients had resection of their primary tumor. At least one sentinel node was found in 28 patients (97%), and the median number of sentinel nodes identified was 2 (range 1-4). One patient had a positive sentinel node on routine hematoxylin and eosin (H&E) staining and developed lung metastases. Two patients had positive sentinel nodes following immunohistochemical staining, and both remain disease free despite not undergoing completion lymphadenectomy. One patient developed a lymph node metastasis after a negative SLNB. For patients with these sarcoma subtypes without radiological evidence of nodal or distant metastases, the incidence of occult lymph node metastasis is relatively low. Determining utility of SLNB may require a multicenter trial. C1 [Maduekwe, Ugwuji N.; Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. [Hornicek, Francis J.; Springfield, Dempsey S.; Raskin, Kevin A.] Massachusetts Gen Hosp, Dept Orthopaed, Div Orthoped Oncol, Boston, MA 02114 USA. [Harmon, David C.; Choy, Edwin] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Rosenberg, Andrew E.; Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [DeLaney, Thomas F.; Chen, Yen-Lin] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Ott, Mark J.] LDS Hosp, Dept Surg, Salt Lake City, UT USA. RP Maduekwe, UN (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. EM syoon@partners.org OI Choy, Edwin/0000-0001-9896-8084 FU Clinical Research Curriculum Award [NIH K30] FX Dr. Maduekwe was supported by an NIH K30 Clinical Research Curriculum Award through the Scholars in Clinical Science Program at Harvard Medical School. NR 41 TC 21 Z9 22 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2009 VL 16 IS 5 BP 1356 EP 1363 DI 10.1245/s10434-009-0393-9 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 428VG UT WOS:000264878900043 PM 19259743 ER PT J AU Slovut, DP Sullivan, TM AF Slovut, David Paul Sullivan, Timothy M. TI Combined Endovascular and Open Revascularization SO ANNALS OF VASCULAR SURGERY LA English DT Review ID THORACOABDOMINAL AORTIC-ANEURYSMS; CORONARY-ARTERY-BYPASS; CRITICAL LIMB ISCHEMIA; AORTOILIAC OCCLUSIVE DISEASE; INTER-SOCIETY-CONSENSUS; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; SYNCHRONOUS CAROTID-ENDARTERECTOMY; AUTOGENOUS COMPOSITE VEIN; ILIAC BALLOON ANGIOPLASTY; ELEPHANT TRUNK TECHNIQUE AB The last decade has borne witness to a transformation in the care of patients with vascular disease. There has been a rapid transition towards minimally invasive techniques as interventionalists obtain increasingly advanced catheter-based skills and access to newer and more sophisticated devices. Patients who are not candidates for completely percutaneous revascularization, or those felt to be at prohibitive risk for traditional surgical reconstruction, may benefit from hybrid therapy, a combination of open surgery and endovascular repair that offers patients the opportunity for complete revascularization with decreased morbidity and mortality. This review examines applications of hybrid procedures for treating patients with disabling claudication and limb-threatening ischemia, aortic arch disease, thoracoabdominal aneurysms, extracranial carotid disease, and coronary artery disease. C1 [Slovut, David Paul] N Shore Med Ctr, Salem, MA 01970 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Minneapolis Heart Inst, Minneapolis, MN USA. RP Slovut, DP (reprint author), N Shore Med Ctr, 81 Highland Ave, Salem, MA 01970 USA. EM david.slovut@mssm.edu NR 102 TC 8 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD MAY-JUN PY 2009 VL 23 IS 3 BP 414 EP 424 DI 10.1016/j.avsg.2008.12.001 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 450LT UT WOS:000266402700035 PM 19359136 ER PT J AU Wang, MH Guo, QL Xu, XG Wang, XY Ye, XY Wu, S Hooper, DC Wang, MG AF Wang, Minghua Guo, Qinglan Xu, Xiaogang Wang, Xiaoying Ye, Xinyu Wu, Shi Hooper, David C. Wang, Minggui TI New Plasmid-Mediated Quinolone Resistance Gene, qnrC, Found in a Clinical Isolate of Proteus mirabilis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; KLEBSIELLA-PNEUMONIAE; STENOTROPHOMONAS-MALTOPHILIA; TRANSFERABLE PLASMID; IN-VIVO; DETERMINANTS; BACTERIA; TRANSPOSITION; INITIATION; SEQUENCE AB Since the discovery of qnrA in 1998, two additional qnr genes, qnrB and qnrS, have been described. These three plasmid-mediated genes contribute to quinolone resistance in gram-negative pathogens worldwide. A clinical strain of Proteus mirabilis was isolated from an outpatient with a urinary tract infection and was susceptible to most antimicrobials but resistant to ampicillin, sulfamethoxazole, and trimethoprim. Plasmid pHS10, harbored by this strain, was transferred to azide-resistant Escherichia coli J53 by conjugation. A transconjugant with pHS10 had low-level quinolone resistance but was negative by PCR for the known qnr genes, aac(6')-Ib-cr and qepA. The ciprofloxacin MIC for the clinical strain and a J53/pHS10 transconjugant was 0.25 mu g/ml, representing an increase of 32-fold relative to that for the recipient, J53. The plasmid was digested with HindIII, and a 4.4-kb DNA fragment containing the new gene was cloned into pUC18 and transformed into E. coli TOP10. Sequencing showed that the responsible 666-bp gene, designated qnrC, encoded a 221-amino-acid protein, QnrC, which shared 64%, 42%, 59%, and 43% amino acid identity with QnrA1, QnrB1, QnrS1, and QnrD, respectively. Upstream of qnrC there existed a new IS3 family insertion sequence, ISPmi1, which encoded a frameshifted transposase. qnrC could not be detected by PCR, however, in 2,020 strains of Enterobacteriaceae. A new quinolone resistance gene, qnrC, was thus characterized from plasmid pHS10 carried by a clinical isolate of P. mirabilis. C1 [Wang, Minghua; Guo, Qinglan; Xu, Xiaogang; Wang, Xiaoying; Ye, Xinyu; Wu, Shi; Wang, Minggui] Fudan Univ, Huashan Hosp, Inst Antibiot, Shanghai 200040, Peoples R China. [Hooper, David C.] Fudan Univ, Inst Biomed Sci, Shanghai 200040, Peoples R China. [Wang, Minggui] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Wang, MG (reprint author), Fudan Univ, Huashan Hosp, Inst Antibiot, 12 M Wulumuqi Rd, Shanghai 200040, Peoples R China. EM mgwang@fudan.edu.cn RI guo, qinglan/E-4857-2012; OI guo, qinglan/0000-0003-2490-1201; Wang, Minggui/0000-0001-7682-5859 FU Ministry of Science and Technology, China [2005CB0523101]; National Natural Science Foundation of China [30572229]; Shanghai Municipal Health Bureau [t LJ06052]; National Institutes of Health, U. S. Public Health Service [AI57576] FX This work was supported by grant 2005CB0523101 (to M. W.) from the National Basic Research Program of China from the Ministry of Science and Technology, China, by grant 30572229 (to M. W.) from the National Natural Science Foundation of China, by grant LJ06052 (to M. W.) from the Shanghai Municipal Health Bureau, and by grant AI57576 (to D. C. H.) from the National Institutes of Health, U. S. Public Health Service. NR 30 TC 170 Z9 202 U1 6 U2 32 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY 1 PY 2009 VL 53 IS 5 BP 1892 EP 1897 DI 10.1128/AAC.01400-08 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 438AQ UT WOS:000265528700024 PM 19258263 ER PT J AU Hughes, DW Frei, CR Maxwell, PR Green, K Patterson, JE Crawford, GE Lewis, JS AF Hughes, Darrel W. Frei, Christopher R. Maxwell, Pamela R. Green, Kay Patterson, Jan E. Crawford, George E. Lewis, James S., II TI Continuous versus Intermittent Infusion of Oxacillin for Treatment of Infective Endocarditis Caused by Methicillin-Susceptible Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIMICROBIAL THERAPY; MEDICAL PROGRESS; DIAGNOSIS; COMPLICATIONS; MANAGEMENT; CRITERIA; SURGERY AB Infective endocarditis (IE) is the fourth leading cause of life-threatening infection in the United States and imposes significant morbidity and mortality. The American Heart Association guidelines for the diagnosis and treatment of IE do not address continuous-infusion (CI) oxacillin. This retrospective study compares outcomes between CI oxacillin and intermittent-infusion (II) oxacillin in the treatment of IE caused by methicillin-susceptible Staphylococcus aureus (MSSA). A total of 709 medical records were reviewed for inpatients with definitive IE treated between 1 January 2000 and 31 December 2007. Continuous data were analyzed by Student's t test or the Wilcoxon rank sum test. The chi-square test or Fisher's exact test was used to compare nominal data. A multivariate logistic model was constructed. One hundred seven patients met eligibility criteria for inclusion into the study. Seventy-eight patients received CI oxacillin, whereas 28 received II oxacillin. CI and II groups were similar with respect to 30-day mortality (8% versus 10%, P = 0.7) and length of stay (20 versus 25 days, P = 0.4) but differed in 30-day microbiological cure (94% versus 79%, P = 0.03). Sixty-three patients received synergistic gentamicin, whereas 44 did not. The gentamicin and no-gentamicin groups were similar with respect to 30-day mortality (11% versus 4%, P = 0.2) and 30-day microbiological cure (90% versus 89%, P = 0.8); however, times to defervescence (4 versus 2 days, P = 0.02) were significantly different. CI oxacillin is an effective alternative to II oxacillin for the treatment of IE caused by MSSA and may improve microbiological cure. This convenient and pharmacodynamically optimized dosing regimen for oxacillin deserves consideration for patients with IE caused by MSSA. C1 [Hughes, Darrel W.; Maxwell, Pamela R.; Green, Kay; Lewis, James S., II] Univ Hlth Syst, Dept Pharm Serv, San Antonio, TX 78229 USA. [Hughes, Darrel W.; Frei, Christopher R.; Maxwell, Pamela R.; Lewis, James S., II] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Hughes, Darrel W.; Frei, Christopher R.; Maxwell, Pamela R.; Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Patterson, Jan E.; Crawford, George E.; Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA. [Patterson, Jan E.; Crawford, George E.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Lewis, JS (reprint author), Univ Hlth Syst, Dept Pharm Serv, 4502 Med Dr, San Antonio, TX 78229 USA. EM james.lewis@uhs-sa.com NR 25 TC 27 Z9 27 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY 1 PY 2009 VL 53 IS 5 BP 2014 EP 2019 DI 10.1128/AAC.01232-08 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 438AQ UT WOS:000265528700040 PM 19258261 ER PT J AU Chen, D Chai, JJ Hart, PJ Zhong, GM AF Chen, Ding Chai, Jijie Hart, P. John Zhong, Guangming TI Identifying catalytic residues in CPAF, a Chlamydia-secreted protease SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Chlamydia; CPAF; Hidden Markov Models; HHPRED; MODELLER; Molecular modeling; Tricorn protease; Catalytic triad; Site-directed mutagenesis; Protein structure prediction ID TRACHOMATIS-INFECTED CELLS; HUMAN-ANTIBODY RESPONSES; CD4(+) T-CELLS; P55 PDZ DOMAIN; MURIDARUM INFECTION; PROTECTIVE IMMUNITY; HOMOLOGY DETECTION; BH3-ONLY PROTEINS; CRYSTAL-STRUCTURE; TRICORN PROTEASE AB A secreted chlamydial protease designated CPAF (Chlamydial Protease/proteasome-like Activity Factor) degrades host proteins, enabling Chlamydia to evade host defenses and replicate. The mechanistic details of CPAF action, however, remain obscure. We used a computational approach to search the protein data bank for structures that are compatible with the CPAF amino acid sequence. The results reveal that CPAF possesses a fold similar to that of the catalytic domains of the tricorn protease from Thermoplasma acidophilum. and that CPAF residues H105, S499, and E558 are structurally analogous to the tricorn protease catalytic triad residues H746. S965, and D1023. Substitution of these putative CPAF catalytic residues blocked CPAF from degrading substrates in vitro, while the wild type and a noncatalytic control mutant of CPAF remained cleavage-competent. Substrate cleavage is also correlated with processing of CPAF into N-terminal (CPAFn) and C-terminal (CPAFc) fragments, suggesting that these putative catalytic residues may also be required for CPAF maturation. (C) 2009 Elsevier Inc. All rights reserved. C1 [Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Chen, Ding; Zhong, Guangming] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Chai, Jijie] Natl Inst Biol Sci, Beijing, Peoples R China. [Hart, P. John] S Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Hart, PJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. EM pjhart@biochem.uthscsa.edu; zhongg@uthscsa.edu FU NIAID NIH HHS [R01 AI047997, R01 AI047997-09, R01 AI064537, R01 AI064537-05] NR 49 TC 18 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 1 PY 2009 VL 485 IS 1 BP 16 EP 23 DI 10.1016/j.abb.2009.01.014 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 441FG UT WOS:000265754100003 PM 19388144 ER PT J AU Goldman, AL Pezawas, L Doz, P Mattay, VS Fischl, B Verchinski, BA Chen, Q Weinberger, DR Meyer-Lindenberg, A AF Goldman, Aaron L. Pezawas, Lukas Doz, Priv Mattay, Venkata S. Fischl, Bruce Verchinski, Beth A. Chen, Qiang Weinberger, Daniel R. Meyer-Lindenberg, Andreas TI Widespread Reductions of Cortical Thickness in Schizophrenia and Spectrum Disorders and Evidence of Heritability SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HUMAN CEREBRAL-CORTEX; MONOZYGOTIC TWINS DISCORDANT; GENETICALLY COMPLEX TRAITS; 1ST EPISODE SCHIZOPHRENIA; MAGNETIC-RESONANCE IMAGES; VOXEL-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS; GRAY-MATTER; UNAFFECTED SIBLINGS; HIPPOCAMPAL VOLUME AB Context: Schizophrenia is a brain disorder with predominantly genetic risk factors, and previous research has identified heritable cortical and subcortical reductions in local brain volume. To our knowledge, cortical thickness, a measure of particular interest in schizophrenia, has not previously been evaluated in terms of its heritability in relationship to risk for schizophrenia. Objective: To quantify the distribution and heritability of cortical thickness changes in schizophrenia. Design: We analyzed a large sample of normal controls, affected patients, and unaffected siblings using a surface-based approach. Cortical thickness was compared between diagnosis groups on a surfacewide node-by-node basis. Heritability related to disease risk was assessed in regions derived from an automated cortical parcellation algorithm by calculating the Risch lambda. Setting: Research hospital. Participants: One hundred ninety-six normal controls, 115 affected patients with schizophrenia, and 192 unaffected siblings. Main Outcome Measure: Regional cortical thickness. Results: Node-by-node mapping statistics revealed widespread thickness reductions in the patient group, most pronouncedly in the frontal lobe and temporal cortex. Unaffected siblings did not significantly differ from normal controls at the chosen conservative threshold. Risch lambda analysis revealed widespread evidence for heritability for cortical thickness reductions throughout the brain. Conclusions: To our knowledge, the present study provides the first evidence of broadly distributed and heritable reductions of cortical thickness alterations in schizophrenia. However, since only trend-level reductions of thickness were observed in siblings, cortical thickness per se (at least as measured by this approach) is not a strong intermediate phenotype for schizophrenia. Arch Gen Psychiatry. 2009; 66(5):467-477 C1 [Goldman, Aaron L.; Pezawas, Lukas; Mattay, Venkata S.; Verchinski, Beth A.; Chen, Qiang; Weinberger, Daniel R.; Meyer-Lindenberg, Andreas] NIMH, Neuroimaging Core Facil, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Fischl, Bruce] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr, Charlestown, MA USA. [Fischl, Bruce] MIT, Dept Hlth Sci & Technol, Cambridge, MA 02139 USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, D-6800 Mannheim, Germany. RP Weinberger, DR (reprint author), NIMH, Neuroimaging Core Facil, Genes Cognit & Psychosis Program, NIH, 10 Ctr Dr,Bldg 10,Room 4S237B, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Meyer-Lindenberg, Andreas/H-1076-2011; OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Pezawas, Lukas/0000-0002-1329-6352 FU National Center for Research Resources [P41RR14075, R01 RR16594-01A1]; NCRR BIRN Morphometric [BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01 EB001550]; National Institute for Neurological Disorders [R01 NS052585-01]; Mental Illness and Neuroscience Discovery Institute; NIH through the NIH Roadmap for Medical Research [U54 EB005149] FX This work was supported by the National Institute of Mental Health Intramural Research Program and used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health (NIH) (http://biowulf.nih.gov). Support for this research was also provided in part by National Center for Research Resources grants P41RR14075, R01 RR16594-01A1, and NCRR BIRN Morphometric Project BIRN002, U24 RR021382; National Institute for Biomedical Imaging and Bioengineering grant R01 EB001550, and National Institute for Neurological Disorders and Stroke grant R01 NS052585-01 as well as the Mental Illness and Neuroscience Discovery Institute and is part of the National Alliance for Medical Image Computing, funded by NIH through the NIH Roadmap for Medical Research, grant U54 EB005149. NR 67 TC 140 Z9 144 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 2009 VL 66 IS 5 BP 467 EP + PG 14 WC Psychiatry SC Psychiatry GA 441RV UT WOS:000265789100002 PM 19414706 ER PT J AU Boster, A Hreha, S Berger, JR Bao, F Penmesta, R Tselis, A Endress, C Zak, I Perumal, J Caon, C Vazquez, J Tyler, KL Racke, MK Millis, S Khan, O AF Boster, Aaron Hreha, Stephanie Berger, Joseph R. Bao, Fen Penmesta, Ramya Tselis, Alexandros Endress, Christina Zak, Imad Perumal, Jai Caon, Christina Vazquez, Jose Tyler, Kenneth L. Racke, Michael K. Millis, Scott Khan, Omar TI Progressive Multifocal Leukoencephalopathy and Relapsing-Remitting Multiple Sclerosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID MAGNETIZATION-TRANSFER RATIO; RHEUMATIC-DISEASES; NATALIZUMAB; PML; PATIENT; LESIONS; VIRUS; AIDS; DEMYELINATION; DIAGNOSIS AB Objective: To identify clinical and magnetic resonance imaging (MRI) features that distinguish progressive multifocal leukoencephalopathy (PML) from relapsing-remitting multiple sclerosis (RRMS). Design: Retrospective medical record review. Setting: Two urban teaching hospitals in Detroit, Michigan. Patients: Forty-five confirmed PML cases and 100 patients with RRMS. Main Outcome Measures: Clinical and MRI features distinguishing PML from RRMS. Results: Overall, monosymptomatic presentations were more common in multiple sclerosis (MS) than PML (85% vs 47%; P<.01). However, patients with PML presented more often with hemiparesis (24% vs 5%; P=.001) and altered mentation (19% vs 0%; P<.0001), whereas brainstem (2% vs 18%; P=.007) presentations were more common in patients with RRMS. Spinal cord and optic neuritis presentations were seen in 18% and 33% of patients with RRMS, respectively, but not in patients with PML (P<.0001). Brain MRI scans, available in 35 (78%) PML cases, revealed 7 lesion types. Large, confluent T2-weighted lesions (74% vs 2%; P<.0001) and deep gray matter lesions (31% vs 7%; P<.001) were more frequent in patients with PML than patients with RRMS. Crescentic cerebellar lesions (23% vs 0%; P<.001) were seen only in patients with PML. Gadolinium-enhancing (23%), transcallosal (9%), and periventricular (9%) lesions were noted in patients with PML. Brain magnetization transfer ratio (MTR) was low in both PML and MS lesions. However, normal-appearing brain tissue MTR in PML was higher than normal-appearing brain tissue MTR in RRMS (44.15% vs 41.04%; P=.002), suggesting that PML may be relatively more focal than MS. Conclusions: There appear to be differences between the clinical and MRI characteristics of PML and RRMS, which may help distinguish new MS activity from PML. Magnetization transfer ratio studies may provide additional clues in improving early detection of PML in patients with preexisting MS and warrant further investigation. C1 [Boster, Aaron; Hreha, Stephanie; Bao, Fen; Penmesta, Ramya; Tselis, Alexandros; Endress, Christina; Zak, Imad; Perumal, Jai; Caon, Christina; Khan, Omar] Wayne State Univ, Sch Med, Dept Neurol, Image Anal Lab,Multiple Sclerosis Ctr, Detroit, MI 48201 USA. [Zak, Imad] Wayne State Univ, Sch Med, Dept Radiol, Detroit, MI 48201 USA. [Millis, Scott] Wayne State Univ, Sch Med, Dept Phys Med & Rehabil, Detroit, MI 48201 USA. [Millis, Scott] Wayne State Univ, Sch Med, Div Biostat & Clin Translat Sci, Detroit, MI 48201 USA. [Boster, Aaron; Hreha, Stephanie; Bao, Fen; Penmesta, Ramya; Tselis, Alexandros; Perumal, Jai; Caon, Christina; Khan, Omar] Detroit Med Ctr, Detroit, MI USA. [Vazquez, Jose] Henry Ford Hosp, Div Infect Dis, Detroit, MI 48202 USA. [Boster, Aaron; Racke, Michael K.] Ohio State Univ, Multiple Sclerosis Ctr, Div Neuroimmunol, Dept Neurol, Columbus, OH 43210 USA. [Berger, Joseph R.] Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY 40506 USA. [Tyler, Kenneth L.] Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. [Tyler, Kenneth L.] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. [Tyler, Kenneth L.] Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. [Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Khan, O (reprint author), Wayne State Univ, Sch Med, Dept Neurol, Image Anal Lab,Multiple Sclerosis Ctr, 4201 St Antoine,8D UHC, Detroit, MI 48201 USA. EM okhan@med.wayne.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU Partners Multiple Sclerosis Fellowship Award; National Multiple Sclerosis Society Sylvia Lawry Fellowship Award; Wayne State University Neuroscience Program FX Dr Boster is a recipient of the Partners Multiple Sclerosis Fellowship Award. Dr Perumal is a recipient of the National Multiple Sclerosis Society Sylvia Lawry Fellowship Award. This study was supported in part by the Wayne State University Neuroscience Program. NR 44 TC 28 Z9 29 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2009 VL 66 IS 5 BP 593 EP 599 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 444PU UT WOS:000265993700007 PM 19433659 ER PT J AU Dong, YL Zhang, GH Zhang, B Moir, RD Xia, WM Marcantonio, ER Culley, DJ Crosby, G Tanzi, RE Xie, ZC AF Dong, Yuanlin Zhang, Guohua Zhang, Bin Moir, Robert D. Xia, Weiming Marcantonio, Edward R. Culley, Deborah J. Crosby, Gregory Tanzi, Rudolph E. Xie, Zhongcong TI The Common Inhalational Anesthetic Sevoflurane Induces Apoptosis and Increases beta-Amyloid Protein Levels SO ARCHIVES OF NEUROLOGY LA English DT Article ID MIDDLE CEREBRAL-ARTERY; LYMPHOCYTES IN-VITRO; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; VOLATILE ANESTHETICS; CASPASE-3 ACTIVATION; ISOFLURANE; ISCHEMIA; RATS; EXPRESSION AB Objective: To assess the effects of sevoflurane, the most commonly used inhalation anesthetic, on apoptosis and beta-amyloid protein (A beta) levels in vitro and in vivo. Subjects: Naive mice, H4 human neuroglioma cells, and H4 human neuroglioma cells stably transfected to express full-length amyloid precursor protein. Interventions: Human H4 neuroglioma cells stably transfected to express full-length amyloid precursor protein were exposed to 4.1% sevoflurane for 6 hours. Mice received 2.5% sevoflurane for 2 hours. Caspase-3 activation, apoptosis, and A beta levels were assessed. Results: Sevoflurane induced apoptosis and elevated levels of beta-site amyloid precursor protein-cleaving enzyme and A beta in vitro and in vivo. The caspase inhibitor Z-VAD decreased the effects of sevoflurane on apoptosis and A beta. Sevoflurane-induced caspase-3 activation was attenuated by the gamma-secretase inhibitor L-685,458 and was potentiated by A beta. These results suggest that sevoflurane induces caspase activation which, in turn, enhances beta-site amyloid precursor protein-cleaving enzyme and A beta levels. Increased A beta levels then induce further rounds of apoptosis. Conclusions: These results suggest that inhalational anesthetic sevoflurane may promote Alzheimer disease neuropathogenesis. If confirmed in human subjects, it may be prudent to caution against the use of sevoflurane as an anesthetic, especially in those suspected of possessing excessive levels of cerebral A beta. C1 [Dong, Yuanlin; Zhang, Guohua; Zhang, Bin; Moir, Robert D.; Tanzi, Rudolph E.; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Massachusetts Gen Inst Neurodegenerat Dis, Boston, MA 02114 USA. [Dong, Yuanlin; Zhang, Guohua; Zhang, Bin; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Xia, Weiming; Marcantonio, Edward R.; Culley, Deborah J.; Crosby, Gregory] Harvard Univ, Sch Med, Boston, MA USA. [Zhang, Guohua] China Med Univ, Dept Forens Pathol, Fac Forens Med, Shenyang, Peoples R China. [Zhang, Bin] Capital Med Univ, Dept Anesthesia, Beijing Friendship Hosp, Beijing, Peoples R China. [Xia, Weiming] Harvard Inst Med, Ctr Neurol Dis, Boston, MA USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Culley, Deborah J.; Crosby, Gregory] Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, Dept Neurol, Geriatr Anaesthesia Res Unit,Dept Anesthesia & Cr, 114 16th St,3750, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu; zxie@partners.org RI xia, weiming/E-5465-2016 OI xia, weiming/0000-0002-7463-3295 FU NIA NIH HHS [AG029856, AG2025, R21 AG029856, R21 AG029856-01A2]; NIGMS NIH HHS [GM077507, GM088801, R01 GM088801, R01 GM088801-01A1]; NINDS NIH HHS [K08 NS048140, K08 NS048140-04, K08 NS048140-05, NS048140] NR 54 TC 102 Z9 118 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2009 VL 66 IS 5 BP 620 EP 631 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 444PU UT WOS:000265993700010 PM 19433662 ER PT J AU Petrie, EC Cross, DJ Galasko, D Schellenberg, GD Raskind, MA Peskind, ER Minoshima, S AF Petrie, Eric C. Cross, Donna J. Galasko, Douglas Schellenberg, Gerard D. Raskind, Murray A. Peskind, Elaine R. Minoshima, Satoshi TI Preclinical Evidence of Alzheimer Changes Convergent Cerebrospinal Fluid Biomarker and Fluorodeoxyglucose Positron Emission Tomography Findings SO ARCHIVES OF NEUROLOGY LA English DT Article ID CEREBRAL GLUCOSE-METABOLISM; POSTERIOR CINGULATE CORTEX; MILD COGNITIVE IMPAIRMENT; CSF PHOSPHORYLATED-TAU; APOLIPOPROTEIN-E; EPSILON-4 ALLELE; DISEASE; PULVINAR; APOE-EPSILON-4; ASSOCIATION AB Background: Alterations in cerebrospinal fluid (CSF) tau and beta-amyloid peptide 1-42 (A beta(42)) levels and rates of cerebral glucose metabolism (CMRglu) on fluorodeoxyglucose positron emission tomography (FDG-PET) occur years before clinical symptoms of Alzheimer disease (AD) become manifest, but their relationship remains unclear. Objective: To determine whether CSF AD biomarker levels and CMRglu in healthy individuals correlate in brain structures affected early in AD. Design: Cohort study. Setting: Alzheimer disease research center. Participants: Twenty individuals without dementia aged 46 to 83 years. Interventions: Lumbar CSF sampling and FDG-PET imaging of CMRglu. The CSF A beta(42), tau, and tau phosphorylated at threonine 181 (ptau(181)) levels were measured using immunobead-based multiplex assays. Main Outcome Measures: Correlations between CMRglu and CSF biomarker levels were analyzed via voxel-based and volume-of-interest approaches. Results: Voxel-based analyses demonstrated significant negative correlations between CSF tau and ptau181 levels and CMRglu in the posterior cingulate, precuneus, and parahippocampal regions. In contrast, a limited positive correlation was found between CSF A beta(42) levels and CMRglu in the inferior temporal cortex. Volume- of-interest analyses confirmed negative associations between CSF tau and ptau181 levels and CMRglu in the parietal and medial parietal lobes and a positive association between CSF A beta(42) levels and CMRglu in the parahippocampal gyrus. Conclusions: In healthy individuals, higher CSF tau and ptau181 concentrations were associated with more severe hypometabolism in several brain regions affected very early in AD, whereas lower CSF A beta(42) concentrations were associated with hypometabolism only in the medial temporal lobe. This suggests that early tau and A beta abnormalities may be associated with subtle synaptic changes in brain regions vulnerable to AD. A longitudinal assessment of CSF and FDG-PET biomarkers is needed to determine whether these changes predict cognitive impairment and incipient AD. C1 [Petrie, Eric C.; Raskind, Murray A.; Peskind, Elaine R.] Vet Affairs Puget Sound Hlth Care Syst, Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Petrie, Eric C.; Raskind, Murray A.; Peskind, Elaine R.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Petrie, Eric C.; Raskind, Murray A.; Peskind, Elaine R.] Univ Washington, Dept Behav Sci, Seattle, WA 98195 USA. [Cross, Donna J.; Minoshima, Satoshi] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Galasko, Douglas] Univ Calif San Diego, Vet Affairs Med Ctr, San Diego, CA 92161 USA. [Galasko, Douglas] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Petrie, EC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Illness Res Educ & Clin Ctr, Mail Code S-182 GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM eric.petrie@med.va.gov FU Office of Research and Development; Medical Research Service; Department of Veterans Affairs [R01 NS045254, P50 AG05136, R01 AG023185, R01 AG05131]; National Institutes of Health [K08 AG023670] FX This material is based on work supported in part by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs; by grants R01 NS045254, P50 AG05136, R01 AG023185, R01 AG05131, and K08 AG023670 from the National Institutes of Health; NR 37 TC 53 Z9 54 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2009 VL 66 IS 5 BP 632 EP 637 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 444PU UT WOS:000265993700011 PM 19433663 ER PT J AU Kesselheim, JC Lehmann, LE Styron, NF Joffe, S AF Kesselheim, Jennifer C. Lehmann, Leslie E. Styron, Nancy Frumer Joffe, Steven TI Is Blood Thicker Than Water? Ethics of Hematopoietic Stem Cell Donation by Biological Siblings of Adopted Children SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID BONE-MARROW DONATION; TRANSPLANTATION; CHILDREN; DONORS C1 [Kesselheim, Jennifer C.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Kesselheim, JC (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM jennifer_kesselheim@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 NR 13 TC 8 Z9 8 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAY PY 2009 VL 163 IS 5 BP 413 EP 416 PG 4 WC Pediatrics SC Pediatrics GA 441RU UT WOS:000265789000002 PM 19414685 ER PT J AU Morse, LR Lazzari, AA Battaglino, R Stolzmann, KL Matthess, KR Gagnon, DR Davis, SA Garshick, E AF Morse, Leslie R. Lazzari, Antonio A. Battaglino, Ricardo Stolzmann, Kelly L. Matthess, Kirby R. Gagnon, David R. Davis, Samuel A. Garshick, Eric TI Dual Energy X-Ray Absorptiometry of the Distal Femur May Be More Reliable than the Proximal Tibia in Spinal Cord Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Bone mineral density; Osteoporosis; Precision; Rehabilitation; Spinal cord injuries ID BONE-MINERAL DENSITY; PRECISION; OSTEOPOROSIS; FRACTURES AB Objective: To evaluate the precision of dual energy x-ray absorptiometry scanning at 2 skeletal sites at the knee (proximal femur and distal tibia) in people with SCI. Design: Cross-sectional. Setting: Veterans Affairs Medical Center. Participants: Subjects (N=20) with chronic SCI. Interventions: Not applicable. Main Outcome Measures: Precision as determined by root mean square coefficient of variation (RMS-CV) and root mean square standard deviation (RMS-SD). Results: At the distal femur the root RMS-CV was 3.01% and the RMS-SD was 0.025g/cm(2). At the proximal tibia the RMS-CV was 5.91% and the RMS-SD was 0.030g/cm(2). Conclusions: Precision at the distal femur is greater than at the proximal tibia and we recommend it as the preferred site for the longitudinal assessment of bone mineral density at the knee in chronic SCI. C1 [Matthess, Kirby R.] Harvard Univ, Sch Med, Programs Res VA Boston, Boston, MA 02118 USA. [Garshick, Eric] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02118 USA. [Morse, Leslie R.; Lazzari, Antonio A.; Stolzmann, Kelly L.; Matthess, Kirby R.; Gagnon, David R.; Davis, Samuel A.; Garshick, Eric] VA Boston Healthcare Syst, Res & Dev Serv, Dept Vet Affairs, Boston, MA USA. [Lazzari, Antonio A.] VA Boston Healthcare Syst, Div Primary Care, Rheumatol Sect, Director Osteoporosis Prevent Clin, Boston, MA USA. [Gagnon, David R.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, VA Cooperat Studies Program, Boston, MA USA. [Garshick, Eric] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Med Serv, Boston, MA USA. [Gagnon, David R.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Battaglino, Ricardo] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. [Morse, Leslie R.] Harvard Univ, Sch Med, Forsyth Inst, Dept Phys Med & Rehabil, Boston, MA 02118 USA. RP Morse, LR (reprint author), Harvard Univ, Sch Med, Forsyth Inst, Dept Phys Med & Rehabil, 140 Fenway, Boston, MA 02118 USA. EM lmorse4@partners.org RI Morse, Leslie/C-9442-2015; battaglino, ricardo/D-2892-2015; OI Morse, Leslie/0000-0002-7426-6341; Gagnon, David/0000-0002-6367-3179 FU Office of Research and Development, Health Services R&D Service, Quality Enhancement Research Initiative [RRP-07-312]; National Institutes of Health [K12 HD001097-08, ROIHD42141, R21 HD057030] FX Supported by the Office of Research and Development, Health Services R&D Service, Quality Enhancement Research Initiative (grant no. RRP-07-312); National Institutes of Health (grant nos. K12 HD001097-08, ROIHD42141, and R21 HD057030). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 15 TC 17 Z9 19 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2009 VL 90 IS 5 BP 827 EP 831 DI 10.1016/j.apmr.2008.12.004 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 443ZS UT WOS:000265949900016 PM 19406303 ER PT J AU Tsai, SJ Ying, TH Huang, YH Cheng, JW Bih, LI Lew, HL AF Tsai, Su-Ju Ying, Tsung-Ho Huang, Yu-Hui Cheng, Ju-Wen Bih, Liu-Ing Lew, Henry L. TI Transperineal Injection of Botulinum Toxin A for Treatment of Detrusor Sphincter Dyssynergia: Localization With Combined Fluoroscopic and Electromyographic Guidance SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Bladder; Botulinum toxin type A; Rehabilitation; Spinal cord injuries; Urethra ID SPINAL-CORD-INJURY; URINARY-TRACT DYSFUNCTION; PUDENDAL NERVE BLOCK; TERM-FOLLOW-UP; DISEASE; MANAGEMENT; MORTALITY; QUALITY; LIFE; MEN AB Objective: To determine the effectiveness of a combined method for localizing external urethral sphincter for transperineal injection of botulinum toxin A (BTX-A) in the treatment of detrusor sphincter dyssynergia (DSD) in patients with spinal cord injury (SCI). Design: A prospective, open-label trial. Setting: A rehabilitation hospital affiliated with a medical university. Participants: Eighteen SCI patients with voiding dysfunction resulting from urodynamically confirmed DSD. Interventions: 100 units of BTX-A injected transperineally into the external urethral sphincter, which was localized using combined fluoroscopic and electromyographic guidance, using a Foley catheter inserted for visualization of vesicourethral anatomy. Main Outcome Measures: (1) postvoid residual volume, (2) leak point pressure, (3) maximal intravesical pressure, (4) maximal urethral pressure, (5) quality of life measures for urination, quantified by the Quality of Life Index (QLI). Results: Positive clinical outcomes were observed in all 18 patients in this study. The mean reductions in postvoid residual volume, leak point pressure, maximal intravesical pressure, and maximal urethral pressure before and after BTX-A injection were 183ml, 37cm H(2)O, 45cm H(2)O, and 92cm H(2)O, respectively (all P values <.05). The mean QLI significantly improved from -0.68 +/- 0.27 to 0.66 +/- 0.19 (P<.01). No significant side effects were noted after injection. The clinical therapeutic effects have shown reductions in occurrence and degree of autonomic dysreflexia, vesicoureteral reflux, hydronephrosis, and urinary tract infection. The bladder management programs also obtained improvements in our patients, either doing intermittent catheterizations less frequently, or resuming spontaneous voiding without indwelling catheters. Conclusion: With this combined method for localization of the external urethral sphincter, transperineal injection of BTX-A was safe, accurate, easy to perform, and effective for treatment of DSD in patients with SCI. C1 [Tsai, Su-Ju; Huang, Yu-Hui; Bih, Liu-Ing] Chung Shan Med Univ Hosp, Dept Phys Med & Rehabil, Taichung 406, Taiwan. [Ying, Tsung-Ho] Chung Shan Med Univ Hosp, Dept Obstet & Gynecol, Taichung 406, Taiwan. [Tsai, Su-Ju; Huang, Yu-Hui; Bih, Liu-Ing] Chung Shan Med Univ, Dept Phys Med & Rehabil, Coll Med, Taichung, Taiwan. [Ying, Tsung-Ho] Chung Shan Med Univ, Inst Biochem & Biotechnol, Coll Med, Taichung, Taiwan. [Cheng, Ju-Wen] Chang Gung Mem Hosp, Dept Phys Med & Rehabil, Kaohsiung, Taiwan. [Lew, Henry L.] VA Boston Healthcare Syst, Phys Med & Rehabil Serv, Boston, MA USA. RP Tsai, SJ (reprint author), Chung Shan Med Univ Hosp, Dept Phys Med & Rehabil, 1142 Sect 3,Tay Yuan Rd, Taichung 406, Taiwan. EM sujutsai@ms71.hinet.net FU National Science Council of the Republic of China [NSC 932314B040007] FX Supported by the National Science Council of the Republic of China (grant no. NSC 932314B040007). NR 25 TC 11 Z9 11 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2009 VL 90 IS 5 BP 832 EP 836 DI 10.1016/j.apmr.2008.10.023 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 443ZS UT WOS:000265949900017 PM 19406304 ER PT J AU Turner, AP Hawkins, EJ Haselkorn, JK Kivlahan, DR AF Turner, Aaron P. Hawkins, Eric J. Haselkorn, Jodie K. Kivlahan, Daniel R. TI Alcohol Misuse and Multiple Sclerosis SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Alcohol; Multiple sclerosis; Rehabilitation; Screening ID AT-RISK DRINKING; IDENTIFICATION TEST AUDIT; PRIMARY-CARE PATIENTS; FORM HEALTH SURVEY; VETERANS-HEALTH; COGNITIVE IMPAIRMENT; SCREENING SCORES; UNITED-STATES; USE DISORDERS; VA PATIENTS AB Objective: To describe the prevalence of alcohol misuse and medical advice to reduce drinking in a national sample of veterans with multiple Sclerosis (MS). Design: Cross-sectional cohort study linking computerized medical record information to mailed survey data from 2004 through 2006. Setting: Veterans Health Administration (VHA). Participants: Two thousand six hundred fifty-five of 4929 veterans with MS who received services in VHA between 2004 and 2006 and also a survey questionnaire (53.9% response rate). Interventions: Not applicable. Main Outcome Measures: Demographic information, Short-Form 12-Item Health Survey Mental Component Summary and Physical Component Summary, Alcohol Use Disorders Identification Test Consumption questions, and questions assessing depressive symptoms and the receipt of alcohol-related advice from a medical professional. Results: Among all survey respondents with MS, the prevalence of alcohol misuse for the sample was 13.9% (confidence interval [CI], 12.5-15.2), with 11.9% (CI, 10.6-13.2) and 2.0% (CI, 1.4-2.5) of participants scoring in the mild/moderate and severe range of alcohol misuse, respectively. In contrast to community samples there was no difference in prevalence by sex. In multivariate logistic regression, age younger than 60 years (<50y; adjusted odds ratio [AOR]=1.66; CI, 1.17-2.37, and 50-59; AOR=1.64; CI, 1.19-2.27), employment (AOR=1.54; Cl, 1.06-2.24) and better physical health (AOR= 1.02; CI, 1.01-1.04) were associated with a higher likelihood of alcohol misuse. Among persons who screened positive for alcohol misuse, only 26.2% (CI, 21.5-30.9) reported they had received advice from a medical provider in the past year to decrease or abstain from drinking. Self-report of advice was more likely among those endorsing severe misuse (AOR=3.65; Cl, 1.85-7.17) and less likely among those with better mental health (AOR=0.97; Cl, 0.94-1.00). Conclusions: Despite the numerous health and social consequences of alcohol misuse, routine screening and intervention for people with MS remain uncommon. Brief screening and advice to reduce or refrain from alcohol use can be accomplished in as little as 5 minutes and can be incorporated into the regular course of medical care. C1 [Turner, Aaron P.; Hawkins, Eric J.; Haselkorn, Jodie K.; Kivlahan, Daniel R.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Turner, Aaron P.; Haselkorn, Jodie K.] Univ Washington, Vet Affairs MS Ctr Excellence W, Seattle, WA 98195 USA. [Turner, Aaron P.; Hawkins, Eric J.; Kivlahan, Daniel R.] Univ Washington, Vet Affairs Ctr Excellence Subst Abuse Treatment, Seattle, WA 98195 USA. [Turner, Aaron P.; Haselkorn, Jodie K.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hawkins, Eric J.; Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@va.gov OI Turner, Aaron/0000-0001-6897-8003 FU Department of Veterans Affairs Rehabilitation Research and Development Service Career Development Award [B4927W] FX Supported by the Department of Veterans Affairs Rehabilitation Research and Development Service Career Development Award (grant no. B4927W). and the Veterans Affairs Center of Excellence in Substance Abuse Treatment and Education, the Veterans Affairs Multiple Sclerosis Center of Excellence West, and the Veterans Affairs Office of Quality and Performance. NR 53 TC 10 Z9 10 U1 3 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2009 VL 90 IS 5 BP 842 EP 848 DI 10.1016/j.apmr.2008.11.017 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 443ZS UT WOS:000265949900019 PM 19406306 ER PT J AU Kuy, S Roman, SA Desai, R Sosa, JA AF Kuy, SreyRam Roman, Sanziana A. Desai, Rani Sosa, Julie Ann TI Outcomes Following Thyroid and Parathyroid Surgery in Pregnant Women SO ARCHIVES OF SURGERY LA English DT Article ID VITAMIN-D DEFICIENCY; PRIMARY HYPERPARATHYROIDISM; ECONOMIC OUTCOMES; UNITED-STATES; CANCER; MANAGEMENT; DISEASE; VALIDATION; RISK AB Objectives: To perform the first population-based measurement of clinical and economic outcomes after thyroid and parathyroid surgery in pregnant women and identify the characteristics of this population and the predictors of outcome. Design: Retrospective cross-sectional study. Setting: Health Care Utilization Project Nationwide Inpatient Sample (HCUP-NIS), a 20% sample of nonfederal US hospitals. Patients: All pregnant women, compared with age-matched nonpregnant women, who underwent thyroid and parathyroid procedures from 1999 to 2005. Main Outcome Measures: Fetal, maternal, and surgical complications, in-hospital mortality, median length of stay, and hospital costs. Results: A total of 201 pregnant women underwent thyroid (n = 165) and parathyroid (n = 36) procedures and were examined together. The mean age was 29 years, 60% were white, 25% were emergent or urgent admissions, and 46% had thyroid cancer. Compared with nonpregnant women (n = 31 155), pregnant patients had a higher rate of endocrine (15.9 vs 8.1%; P < .001) and general complications (11.4 vs 3.6%; P < .001), longer unadjusted lengths of stay (2 days vs 1 day; P < .001), and higher unadjusted hospital costs ($6873 vs $5963; P = .007). The fetal and maternal complication rates were 5.5% and 4.5%, respectively. On multivariate regression analysis, pregnancy was an independent predictor of higher combined surgical complications (odds ratio, 2; P < .001), longer adjusted length of stay (0.3 days longer; P < .001), and higher adjusted hospital costs ($300; P < .001). Other independent predictors of outcome were surgeon volume, patient race or ethnicity, and insurance status. Conclusions: Pregnant women have worse clinical and economic outcomes following thyroid and parathyroid surgery than nonpregnant women, with disparities in outcomes based on race, insurance, and access to high-volume surgeons. C1 [Roman, Sanziana A.; Sosa, Julie Ann] Yale Univ, Sch Med, Dept Surg, Div Endocrine Surg, New Haven, CT 06520 USA. [Kuy, SreyRam; Desai, Rani] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06520 USA. [Desai, Rani] Yale Univ, Sch Med, Sch Epidemiol, New Haven, CT 06520 USA. [Kuy, SreyRam] US Dept Vet Affairs, Washington, DC USA. [Kuy, SreyRam] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Desai, Rani] Vet Affairs Connecticut Syst, Newington, CT USA. RP Roman, SA (reprint author), Yale Univ, Sch Med, Dept Surg, Div Endocrine Surg, 333 Cedar St,POB 208062, New Haven, CT 06520 USA. EM sanziana.roman@yale.edu FU Robert Wood Johnson Foundation; United States Department of Veterans Affairs FX This study was supported by the Robert Wood Johnson Foundation and the United States Department of Veterans Affairs. NR 38 TC 45 Z9 51 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2009 VL 144 IS 5 BP 399 EP 406 PG 8 WC Surgery SC Surgery GA 447QS UT WOS:000266207500002 PM 19451480 ER PT J AU Velmahos, GC Tabbara, M Gross, R Willette, P Hirsch, E Burke, P Emhoff, T Gupta, R Winchell, RJ Patterson, LA Manon-Matos, Y Alam, HB Rosenblatt, M Hurst, J Brotman, S Crookes, B Sartorelli, K Chang, Y AF Velmahos, George C. Tabbara, Malek Gross, Ronald Willette, Paul Hirsch, Erwin Burke, Peter Emhoff, Timothy Gupta, Rajan Winchell, Robert J. Patterson, Lisa A. Manon-Matos, Yorrell Alam, Hasan B. Rosenblatt, Michael Hurst, James Brotman, Sheldon Crookes, Bruce Sartorelli, Kennith Chang, Yuchiao TI Blunt Pancreatoduodenal Injury A Multicenter Study of the Research Consortium of New England Centers for Trauma (ReCONECT) SO ARCHIVES OF SURGERY LA English DT Article ID PANCREATIC TRAUMA; ABDOMINAL-TRAUMA; COMPUTED-TOMOGRAPHY; MANAGEMENT; DIAGNOSIS; EXPERIENCE; RUPTURE; TRENDS; BOWEL; ERA AB Objectives: To evaluate the safety of nonoperative management (NOM), to examine the diagnostic sensitivity of computed tomography (CT), and to identify missed diagnoses and related outcomes in patients with blunt pancreatoduodenal injury (BPDI). Design: Retrospective multicenter study. Setting: Eleven New England trauma centers (7 academic and 4 nonacademic). Patients: Two hundred thirty patients (> 15 years old) with BPDI admitted to the hospital during 11 years. Each BPDI was graded from 1 (lowest) to 5 (highest) according to the American Association for the Surgery of Trauma grading system. Main Outcome Measures: Success of NOM, sensitivity of CT, BPDI-related complications, length of hospital stay, and mortality. Results: Ninety-seven patients (42.2%) with mostly grades 1 and 2 BPDI were selected for NOM: NOM failed in 10 (10.3%), 10 (10.3%) developed BPDI-related complications (3 in patients in whom NOM failed), and 7 (7.2%) died (none related to failure of NOM). The remaining 133 patients were operated on urgently: 34 (25.6%) developed BPDI-related complications and 20 (15.0%) died. The initial CT missed BPDI in 30 patients (13.0%); 4 of them (13.3%) died but not because of the BPDI. The mortality rate in patients without a missed diagnosis was 8.8% (P=.50). There was no correlation between time to diagnosis and length of hospital stay (Spearman r=0.06; P=.43). The sensitivity of CT for BPDI was 75.7% (76% for pancreatic and 70% for duodenal injuries). Conclusions: The NOM of low-grade BPDI is safe despite occasional failures. Missed diagnosis of BPDI continues to occur despite advances in CT but does not seem to cause adverse outcomes in most patients. C1 [Velmahos, George C.; Tabbara, Malek; Alam, Hasan B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Gross, Ronald; Willette, Paul] Hartford Hosp, Hartford, CT 06115 USA. [Gross, Ronald; Willette, Paul] Univ Connecticut, Hartford, CT 06112 USA. [Hirsch, Erwin; Burke, Peter] Boston Med Ctr, Boston, MA USA. [Hirsch, Erwin; Burke, Peter] Boston Univ, Boston, MA 02215 USA. [Emhoff, Timothy] Univ Massachusetts, Mem Hosp, Worcester, MA USA. [Gupta, Rajan] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Winchell, Robert J.] Maine Med Ctr, Portland, ME USA. [Patterson, Lisa A.; Manon-Matos, Yorrell] Baystate Med Ctr, Springfield, MA USA. [Rosenblatt, Michael] Lahey Clin Med Ctr, Burlington, MA 01803 USA. [Hurst, James] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Velmahos, George C.; Tabbara, Malek; Alam, Hasan B.; Hurst, James; Chang, Yuchiao] Harvard Univ, Sch Med, Boston, MA USA. [Brotman, Sheldon] Berkshires Med Ctr, Pittsfield, MA USA. [Crookes, Bruce; Sartorelli, Kennith] Fletcher Allen Healthcare, Burlington, VT USA. [Crookes, Bruce; Sartorelli, Kennith] Univ Vermont, Burlington, VT 05405 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 21 TC 20 Z9 25 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2009 VL 144 IS 5 BP 413 EP 419 PG 7 WC Surgery SC Surgery GA 447QS UT WOS:000266207500007 PM 19451482 ER PT J AU Nehra, D Goldstein, AM Doody, DP Ryan, DP Chang, YC Masiakos, PT AF Nehra, Deepika Goldstein, Allan M. Doody, Daniel P. Ryan, Daniel P. Chang, Yuchiao Masiakos, Peter T. TI Extracorporeal Membrane Oxygenation for Nonneonatal Acute Respiratory Failure The Massachusetts General Hospital Experience From 1990 to 2008 SO ARCHIVES OF SURGERY LA English DT Article ID ACUTE LUNG INJURY; DISTRESS-SYNDROME; CLINICAL-TRIAL; VENTILATION; OUTCOMES; MORTALITY; SUPPORT; ECMO AB Objective: To determine the efficacy of extracorporeal membrane oxygenation (ECMO) for nonneonatal acute respiratory failure. Design: Single-institution, retrospective medical record review from February 1990 to March 2008. Setting: Tertiary care hospital. Patients: Eighty-one nonneonatal patients (mean age, 23 years; age range, 2 months to 61 years) with acute respiratory failure who had failed maximal ventilator support received ECMO therapy between 1990 and 2008. Patients were grouped into 6 categories based on diagnosis: sepsis (n = 8), bacterial or fungal pneumonia (n = 15), viral pneumonia (n = 9), trauma or burn (n = 10), immunocompromise (n = 15), and other (n = 24). Main Outcome Measure: Survival to hospital discharge. Results: Overall survival was 53%. Survival was highest in patients with viral pneumonia (78%), followed by bacterial pneumonia (53%), sepsis syndrome (44%), and immunocompromise (40%). Patients treated following trauma or burns had the lowest survival (33%). The average age was 19 years for survivors as compared with 27 years for nonsurvivors. Survival was lower in patients with multiple organ failure as compared with those with single organ failure (33% vs 60%, respectively), in patients who experienced mechanical ventilation for longer than 10 days prior to the initiation of ECMO as compared with those who received ventilatory support for less than 10 days prior to the initiation of ECMO(31% vs 57%, respectively), and in patients requiring more than 400 hours of ECMO support as compared with those requiring less than 400 hours of ECMO support (42% vs 55%, respectively). Conclusions: Therapy with ECMO may provide a survival benefit in carefully selected patients with nonneonatal acute respiratory failure who have failed maximal ventilator support. Nonneonatal survival with ECMO therapy is strongly dependent on diagnosis, with the highest survival seen in those with viral or bacterial pneumonia. Older age, multiple organ failure, prolonged ventilation prior to ECMO initiation, and long ECMO runs are associated with decreased survival. C1 [Nehra, Deepika; Goldstein, Allan M.; Doody, Daniel P.; Ryan, Daniel P.; Masiakos, Peter T.] Massachusetts Gen Hosp, Div Pediat Surg, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Masiakos, PT (reprint author), Massachusetts Gen Hosp, Div Pediat Surg, WRN 11,55 Fruit St, Boston, MA 02114 USA. EM pmasiakos@partners.org NR 17 TC 32 Z9 38 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2009 VL 144 IS 5 BP 427 EP 432 PG 6 WC Surgery SC Surgery GA 447QS UT WOS:000266207500011 PM 19451484 ER PT J AU Sailhamer, EA Carson, K Chang, Y Zacharias, N Spaniolas, K Tabbara, M Alam, HB DeMoya, MA Velmahos, GC AF Sailhamer, Elizabeth A. Carson, Katherine Chang, Yuchiao Zacharias, Nikolaos Spaniolas, Konstantinos Tabbara, Malek Alam, Hasan B. DeMoya, Marc A. Velmahos, George C. TI Fulminant Clostridium difficile Colitis Patterns of Care and Predictors of Mortality SO ARCHIVES OF SURGERY LA English DT Article ID PSEUDOMEMBRANOUS COLITIS; COLECTOMY; DIARRHEA AB Hypothesis: There exist predictors of mortality and the need for colectomy among patients with fulminant Clostridium difficile colitis. Design: Retrospective study. Setting: Academic tertiary referral center. Patients: We reviewed the records of 4796 inpatients diagnosed as having C difficile colitis from January 1, 1996, to December 31, 2007, and identified 199 (4.1%) with fulminant C difficile colitis, as defined by the need for colectomy or admission to the intensive care unit for C difficile colitis. Main Outcome Measures: Risk of inpatient mortality was determined by multivariate analysis according to clinical predictors, colectomy, and medical team. Results: The in hospital mortality rate for fulminant C difficile colitis was 34.7%. Independent predictors of mortality included the following: (1) age of 70 years or older, (2) severe leukocytosis or leukopenia (white blood cell count, >= 35000/mu L or <4000/mu L) or bandemia (neutrophil bands, >= 10%), and (3) cardiorespiratory failure (intubation or vasopressors). When all 3 factors were present, the mortality rate was 57.1%; when all 3 were absent, the mortality rate was 0%. Patients who underwent colectomy had a trend toward decreased mortality rates (odds ratio, 0.49; 95% confidence interval, 0.21-1.1; P = .08). Among patients admitted primarily for fulminant C difficile colitis, care in the surgical department compared with the nonsurgical department resulted in a higher rate of operation (85.1% vs 11.2%; P < .001) and lower mortality rates (12.8% vs 39.3%; P = .001). Patients admitted directly to the surgical department had a shorter mean (SD) interval from admission to operation (0 vs 1.7[2.8] days; P = .001). Conclusions: Despite awareness and treatment, fulminant C difficile colitis remains a highly lethal disease. Reliable predictors of mortality exist and should be used to prompt aggressive surgical intervention. Survival rates are higher in patients who were cared for by surgical vs nonsurgical departments, possibly because of more frequent and earlier operations. C1 [Sailhamer, Elizabeth A.; Carson, Katherine; Zacharias, Nikolaos; Spaniolas, Konstantinos; Tabbara, Malek; Alam, Hasan B.; DeMoya, Marc A.; Velmahos, George C.] Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02115 USA. [Chang, Yuchiao] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Biostat,Gen Med Div, Boston, MA 02115 USA. RP Sailhamer, EA (reprint author), 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM esailhamer@partners.org FU NIGMS NIH HHS [F32 GM79880] NR 18 TC 93 Z9 94 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2009 VL 144 IS 5 BP 433 EP 439 PG 7 WC Surgery SC Surgery GA 447QS UT WOS:000266207500013 PM 19451485 ER PT J AU Konstantinidis, IT Deshpande, V Genevay, M Berger, D Fernandez-del Castillo, C Tanabe, KK Zheng, H Lauwers, GY Ferrone, CR AF Konstantinidis, Ioannis T. Deshpande, Vikram Genevay, Muriel Berger, David Fernandez-del Castillo, Carlos Tanabe, Kenneth K. Zheng, Hui Lauwers, Gregory Y. Ferrone, Cristina R. TI Trends in Presentation and Survival for Gallbladder Cancer During a Period of More Than 4 Decades A Single-Institution Experience SO ARCHIVES OF SURGERY LA English DT Article ID EXTRAHEPATIC BILE-DUCT; LAPAROSCOPIC CHOLECYSTECTOMY; CURATIVE RESECTION; CARCINOMA; CHEMOTHERAPY; RECURRENCE; OPERATION; DIAGNOSIS; PATTERNS; DISEASE AB Objectives: To determine the prevalence of incidentally found cases of gallbladder cancer, the incidence of residual disease at reexploration, and the changes in the mode of presentation, treatment, and survival of patients with gallbladder cancer during a period of more than 4 decades. Design: Retrospective case series. Setting: University-affiliated tertiary care center. Patients: Between January 1, 1962, and March 1, 2008, 402 patients with gallbladder cancer were identified and their clinicopathologic data were analyzed. Interventions: Surgical treatment, radiotherapy, and chemotherapy. Main Outcome Measures: Incidentally discovered gallbladder cancer, incidence of residual disease, and differences in presentation, treatment, and survival. Results: Surgical exploration was performed in 260 patients (64.7%), of whom 151 (58.1%) underwent resection. The median age of the patients was 72 years, and 72.3% were female. Between January 1, 1994, and March 1, 2008, 6881 laparoscopic cholecystectomies were performed, and there were 17 incidentally discovered cases of gallbladder cancer (0.25%). Residual disease on reexploration was identified in 0 of 2 patients with T1 tumor, 3 of 13 patients with T2 tumor, and 8 of 10 patients with T3 tumor (P = .01). Patients with stage IV disease (34 [13.1%] diagnosed from 1962-1979; 34 [13.1%] diagnosed from 1980-1997; and 22 [8.5%] diagnosed from 1998-2008) had a median survival of 4 months (range, 0-37 months). Concomitant liver resections increased in the third study period (11.1%, 10.1%, and 54.3%; P < .001), with an increase in negative margins (33.3%, 42.0%, and 63.0%; P = .01). Cox regression analysis identified T stage and surgical margin status as significant prognostic factors. Conclusions: Gallbladder cancer is incidentally found during 0.25% of laparoscopic cholecystectomies. As T stage increases, the likelihood of residual disease on reexploration increases. Although many patients with gallbladder cancer present with incurable disease and have very poor survival, the overall prognosis is improving, likely because of more extensive operations. C1 [Konstantinidis, Ioannis T.; Berger, David; Fernandez-del Castillo, Carlos; Tanabe, Kenneth K.; Ferrone, Cristina R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Deshpande, Vikram; Genevay, Muriel; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zheng, Hui] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Genevay, Muriel] Univ Hosp Geneva, Serv Clin Pathol, Geneva, Switzerland. RP Ferrone, CR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Wing 460,15 Parkman St, Boston, MA 02114 USA. EM cferrone@partners.org NR 31 TC 29 Z9 33 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2009 VL 144 IS 5 BP 441 EP 447 PG 7 WC Surgery SC Surgery GA 447QS UT WOS:000266207500015 PM 19451486 ER PT J AU Ferrone, CR Correa-Gallego, C Warshaw, AL Brugge, WR Forcione, DG Thayer, SP Fernandez-del Castillo, C AF Ferrone, Cristina R. Correa-Gallego, Camilo Warshaw, Andrew L. Brugge, William R. Forcione, David G. Thayer, Sarah P. Fernandez-del Castillo, Carlos TI Current Trends in Pancreatic Cystic Neoplasms SO ARCHIVES OF SURGERY LA English DT Article ID PAPILLARY MUCINOUS NEOPLASMS; POSITRON-EMISSION-TOMOGRAPHY; MANAGEMENT; DIAGNOSIS; TUMORS; RESECTION; LESIONS; DUCT; PSEUDOCYSTS; MALIGNANCY AB Objective: To define how patients with pancreatic cysts are being diagnosed and treated. Design: Retrospective case series. Setting: University-affiliated tertiary care center. Patients: Four hundred one patients evaluated in the Department of Surgery between January 2004 and December 2007. Main Outcome Measures: Clinical management, histological diagnosis, and results of surveillance. Results: Pancreatic cysts were incidentally discovered in 71% (284 of 401) of patients. There was no statistically significant difference in age (60.4 vs 63.1 years; P = .10), cyst size (31 vs 27 mm; P = .12), or histological diagnosis between symptomatic patients and patients with incidentally discovered cysts. Whereas the majority of symptomatic patients had their cystic neoplasms resected on diagnosis, 50% (142 of 284) of incidentally discovered cysts were initially managed nonoperatively. Of the patients who were managed with surveillance, 13 (8%) subsequently underwent resection after a median of 2.1 years because of an increase in cyst size, development of symptoms, increasing tumor markers, worrisome endoscopic ultrasonography findings, or patient anxiety. The most common diagnosis among resected lesions was either main-duct intraductal papillary mucinous neoplasm (25%) or branch-duct intraductal papillary mucinous neoplasm (23%). Invasive cancer was found in 29 of 256 (11%) resected cystic neoplasms, 9 of which were incidentally discovered, and in 7% (1 of 13) of patients who underwent watchful waiting prior to resection. Conclusions: Incidentally discovered pancreatic cystic neoplasms composed 71% of our series, of which 50% were immediately resected. Subsequent morphologic changes or development of symptoms prompted an operation in 8% of patients after a period of surveillance. Invasive malignancy was present in 11% of all resected specimens but in 38% of main-duct intraductal papillary mucinous neoplasms. C1 [Ferrone, Cristina R.; Correa-Gallego, Camilo; Warshaw, Andrew L.; Thayer, Sarah P.; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Brugge, William R.; Forcione, David G.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WAC460, Boston, MA 02114 USA. EM cferrone@partners.org FU NCI NIH HHS [P01 CA117969]; NIDDK NIH HHS [K08 DK071329] NR 24 TC 71 Z9 74 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2009 VL 144 IS 5 BP 448 EP 454 PG 7 WC Surgery SC Surgery GA 447QS UT WOS:000266207500017 PM 19451487 ER PT J AU Saidi, R Kawai, T Kennealey, P Tsouflas, G Elias, N Hertl, M Cosimi, AB Ko, DSC AF Saidi, Reza Kawai, Tatsuo Kennealey, Peter Tsouflas, Georgios Elias, Nahel Hertl, Martin Cosimi, A. B. Ko, Dicken S. C. TI Living Donor Kidney Transplantation With Multiple Arteries Recent Increase in Modern Era of Laparoscopic Donor Nephrectomy SO ARCHIVES OF SURGERY LA English DT Article ID RENAL-ARTERIES; URETERAL COMPLICATIONS; EXPERIENCE; RECIPIENT; OUTCOMES AB Objective: To compare the outcome of living donor kidney transplantation using allografts with a single artery with that observed in recipients of allografts with multiple arteries. Design: Retrospective analysis. Setting: Tertiary center. Patients: Three hundred fifty patients who underwent living donor kidney transplantation from January 2000 to March 2007. Interventions: Living donor kidney transplantation. Main Outcome Measures: Surgical complications and allograft survival. Results: Three hundred nineteen allografts (91.1%) had a single artery (group 1) and 31 (8.9%) had multiple arteries (group 2), including 2 arteries in 21 grafts (67.8%), 3 arteries in 6 (19.3%), and 4 arteries in 4 grafts (12.9%). The operative time was shorter in group 1 compared with group 2 (mean [SD], 173 [35] vs 259 [48] minutes; P < .001). The overall surgical complication rate in groups 1 and 2 was comparable (9.6% vs 9.7%; vascular, 2.8% vs 3.2%; urological, 1.6% vs 3.2%; symptomatic lymphocele, 2.8% vs 3.2%; and wound infections, 2.8% vs 3.2%). The actuarial 1- and 5-year allograft survival rates were comparable in both groups (98.4% and 91.5% in group 1 and 96.8% and 87.1% in group 2). A significant increased use of allografts with multiple arteries has been observed in recent years: 7.8% (n = 10) in grafts that were procured by open technique (n = 127), 4.1% (n = 5) during our initial experience with laparoscopic nephrectomy (n = 123), and 16% (n = 16) in the most recent 100 cases (P < .01). Conclusions: Living donor kidney transplantation in the presence of multiple renal arteries is feasible and safe. Additionally, graft survival and graft function are not adversely affected by the presence of multiple renal arteries in grafts procured laparoscopically. Recently, there has been an increased use of kidneys with multiple arteries with excellent results. C1 [Saidi, Reza; Kawai, Tatsuo; Kennealey, Peter; Tsouflas, Georgios; Elias, Nahel; Hertl, Martin; Cosimi, A. B.; Ko, Dicken S. C.] Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. RP Ko, DSC (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Blake 655,55 Fruit St, Boston, MA 02114 USA. EM dko@partners.org NR 17 TC 26 Z9 28 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2009 VL 144 IS 5 BP 472 EP 475 PG 4 WC Surgery SC Surgery GA 447QS UT WOS:000266207500021 PM 19451491 ER PT J AU Shlipak, MG Katz, R Kestenbaum, B Fried, LF Siscovick, D Sarnak, MJ AF Shlipak, Michael G. Katz, Ronit Kestenbaum, Bryan Fried, Linda F. Siscovick, David Sarnak, Mark J. TI Clinical and subclinical cardiovascular disease and kidney function decline in the elderly SO ATHEROSCLEROSIS LA English DT Article DE Cystatin C; Kidney disease; Atherosclerosis ID STAGE RENAL-DISEASE; VASCULAR-DISEASE; RISK-FACTORS; RENOVASCULAR DISEASE; CYSTATIN-C; MEASUREMENT ERROR; UNITED-STATES; PROGRESSION; POPULATION; MORTALITY AB Objective: Kidney function decline in elderly persons maybe the result of microvascular atherosclerosis. As a proxy for the renovascular system, we evaluated the association of clinical and subclinical cardiovascular disease (CVD) with kidney function decline. Methods: This study included 4380 subjects from the Cardiovascular Health Study, a longitudinal, community-based cohort of persons aged >= 65 from 4 U.S. communities. Creatinine and cystatin C were measured at baseline, year 3, and year 7; eligible subjects had at least two measures. Creatinine-based estimated glomerular filtration Fate (eGFR(creat)) was calculated using the MDRD equation. Rapid kidney function decline was defined as an annual eGFR loss >3 mL/min/1.73 m(2). Predictors of rapid kidney decline included prevalent and subclinical measures of CVD. Results: Mean decline in eGFR(creat) was 0.4 +/- 2.6/year; 714 (16%) had rapid progression. In multivariate models adjusted for demographics, cardiovascular risk factors, and inflammation, prevalent stroke (OR, 95% Cl: 1.55, 1.16-2.08) and heart failure (OR, 95% Cl: 1.80, 1.40-2.31) were independent predictors of rapid kidney decline. Among persons without clinical CV, the subclinical disease measures ankle-arm index <0.9 (OR, 95% Cl: 1.67, 1.25-2.24), common carotid intima-media thickness (>= 1.14 mm) (OR, 95% Cl: 1.52, 1.12-2.06) and internal carotid intima-media thickness (>1.82 mm) (OR, 95% Cl: 1.50, 1.12-2.02) had independent associations with rapid kidney function decline. Results were similar using cystatin C. Conclusion: Clinical atherosclerosis and heart failure and subclinical measures of CVD have independent associations with kidney function decline progression in the elderly, suggesting an underlying role of renal atherosclerosis. Published by Elsevier Ireland Ltd. C1 [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Kestenbaum, Bryan] Vet Affairs Puget Sound Healthcare Syst, Div Nephrol, Seattle, WA USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Siscovick, David] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Sarnak, Mark J.] Tufts Univ New England Med Ctr, Div Nephrol, Boston, MA USA. RP Shlipak, MG (reprint author), VA Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU American Heart Association [R01 DK066488, R01AG027002, K24DK078204-01]; National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295] FX Dr. Shlipak is supported by the American Heart Association Established Investigator Award and by R01 DK066488. Drs. Sarnak, Fried, Shlipak, Siscovick and Newman are also Supported by R01AG027002. Dr. Sarnak is supported by K24DK078204-01. Dr. Fried is supported by an Advanced Research Career Development award from the Office of Research and Development, Clinical Science Research and Development, of the Department of Veterans Affairs. The Cardiovascular Health Study was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant number U01 HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chsnhlbi.org/pi.htm. NR 30 TC 51 Z9 55 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2009 VL 204 IS 1 BP 298 EP 303 DI 10.1016/j.atherosclerosis.2008.08.016 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 454GJ UT WOS:000266670100051 PM 18848325 ER PT J AU Kao, SY AF Kao, Shyan-Yuan TI Regulation of DNA repair by parkin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Parkinson disease; Parkin; DNA excision repair; PCNA ID RECESSIVE JUVENILE PARKINSONISM; TUMOR-SUPPRESSOR GENE; VIRUS TYPE-1 TAX; MONOUBIQUITINATED PCNA; ALPHA-SYNUCLEIN; DEFICIENT MICE; HUMAN BRAIN; PROTEIN; UBIQUITIN; NEURONS AB Mutation of parkin is one of the most prevalent causes of autosomal recessive Parkinson's disease (PD). Parkin is an E3 ubiquitin ligase that acts on a variety of substrates, resulting in polyubiquitination and degradation by the proteasome or monoubiquitination and regulation of biological activity. However, the cellular functions of parkin that relate to its pathological involvement in PD, are not well understood. Here we show that parkin is essential for optimal repair of DNA damage. Parkin-deficient cells exhibit reduced DNA excision repair that can be restored by transfection of wild-type parkin, but not by transfection of a pathological parkin mutant. Parkin also protects against DNA damage-induced cell death, an activity that is largely lost in the pathological mutant. Moreover, parkin interacts with the proliferating cell nuclear antigen (PCNA), a protein that coordinates DNA excision repair. These results suggest that parkin promotes DNA repair and protects against genotoxicity, and implicate DNA damage as a potential pathogenic mechanism in PD. (C) 2009 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Kao, SY (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM shyan-yuan_kao@meei.harvard.edu NR 26 TC 18 Z9 19 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 MAY 1 PY 2009 VL 382 IS 2 BP 321 EP 325 DI 10.1016/j.bbrc.2009.03.048 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 434MR UT WOS:000265279300018 PM 19285961 ER PT J AU Perlis, RH Fijal, B Adams, DH Sutton, VK Trivedi, MH Houston, JP AF Perlis, Roy H. Fijal, Bonnie Adams, David H. Sutton, Virginia K. Trivedi, Madhukar H. Houston, John P. TI Variation in Catechol-O-Methyltransferase Is Associated with Duloxetine Response in a Clinical Trial for Major Depressive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Antidepressant; genetic association; genomics; response; single nucleotide polymorphism ID STAR-ASTERISK-D; ANTIDEPRESSANT TREATMENT; GENETIC-VARIATION; HUMAN BRAIN; COMT GENE; SCHIZOPHRENIA; POLYMORPHISM; HAPLOTYPE; TRANSPORTER; EXPRESSION AB Background: The study objective was to evaluate variations in genes implicated in antidepressant mechanism of action for association with response to duloxetine treatment in major depressive disorder (MDD). Methods: We assessed response over 6 weeks in 250 duloxetine-treated Caucasian patients in a randomized, double-blind study of patients with MDD. Single nucleotide polymorphisms (SNPs) were genotyped in 19 candidate genes selected based on evidence for involvement in antidepressant mechanism of action. Primary analysis examined baseline to end point reduction in the 17-item Hamilton Depression Rating Scale (HAMD17) total score, using a set-based test for association for each gene. Follow-up analyses examined individual SNPs within any significant gene for association with reduction in HAMD17 and 30-item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C-30). Results: After correction for multiple comparisons, only COMT was associated with change in HAMD17 (experimentwide p = .018). Peak association was detected with rs165599 (p = .006), which accounted for approximately 3% of variance in HAMD17 change and >4% of variance in IDS-C-30 change (p = .001). The least-squared mean change (SE) in HAMD17 score by rs165599 genotype was -10.8 (1.2), -8.7 (.6), and -6.5 (.7) for patients with GG, GA, and AA genotypes, respectively. For SNPs in serotonin 2A receptor (HTR2A) previously associated with citalopram response, including rs7997012, no significant evidence of association with duloxetine response was identified. Conclusions: Single nucleotide polymorphisms in COMT were associated with symptom change in duloxetine-treated patients with MDD. If replicated, the magnitude of the COMT genotype effect is of clinical relevance. C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Dept Psychiat, Boston, MA 02144 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02144 USA. [Fijal, Bonnie; Adams, David H.; Houston, John P.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Sutton, Virginia K.] i3 Res, Cary, NC USA. [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, Dept Psychiat, Boston, MA 02144 USA. EM rperlis@partners.org FU Eli Lilly and Company FX This work was sponsored by Eli Lilly and Company. NR 30 TC 55 Z9 59 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2009 VL 65 IS 9 BP 785 EP 791 DI 10.1016/j.biopsych.2008.10.002 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 433XP UT WOS:000265239400009 PM 19095219 ER PT J AU Kim, YW Verdine, GL AF Kim, Young-Woo Verdine, Gregory L. TI Stereochemical effects of all-hydrocarbon tethers in i,i+4 stapled peptides SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Stapled peptides; alpha-Helix; Stereochemical effects; Helicity; Cellular uptake mechanism ID BH3 HELIX AB The stereochemical effects of the hydrocarbon crosslink on the conformation and cellular uptake of i,i+4 stapled peptides were studied. Compared to its S, S-configurated counterpart, the crosslink bearing the R,R-configuration provided a significantly diminished helix stabilizing effect and conferred less efficient cellular uptake on the stapled peptides. These results suggest that the vesicular trafficking pathway employed by cells to take up stapled peptides is sensitive to the extent of helical character in the peptide, with greater helicity conferring increased cellular uptake. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Kim, Young-Woo; Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kim, Young-Woo; Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. RP Verdine, GL (reprint author), Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA. EM verdine@chemistry.harvard.edu FU Harvard and Dana-Farber Program in Cancer Chemical Biology FX This research was supported by the Harvard and Dana-Farber Program in Cancer Chemical Biology. NR 15 TC 41 Z9 41 U1 1 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 1 PY 2009 VL 19 IS 9 BP 2533 EP 2536 DI 10.1016/j.bmcl.2009.03.022 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 432MA UT WOS:000265137100034 PM 19332370 ER PT J AU Biederman, J Petty, CR Wilens, TE Spencer, T Henin, A Faraone, SV Mick, E Monuteaux, MC Kenealy, D Mirto, T Wozniak, J AF Biederman, Joseph Petty, Carter R. Wilens, Timothy E. Spencer, Thomas Henin, Aude Faraone, Stephen V. Mick, Eric Monuteaux, Michael C. Kenealy, Deborah Mirto, Tara Wozniak, Janet TI Examination of concordance between maternal and youth reports in the diagnosis of pediatric bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE maternal report; pediatric bipolar disorder ID SELF-REPORT; PARENT; ADOLESCENTS; SYMPTOMS AB While concordance between mother and child report continues to be the gold standard in the assessment of pediatric bipolar disorder, uncertainty develops when a mother's report is not endorsed by the youth. To this end we compared discordant (mother positive and youth negative) and concordant (mother and youth positive) cases. Subjects were 98 adolescents (12-19 years of age) derived from family studies of bipolar disorder in youth who had both self-reported and mother-reported assessments. Comparisons were made between discordant (n = 35) and concordant (n = 59) cases on a wide range of clinical correlates. Mothers in both groups reported similar rates of symptoms of mania and depression. Within the concordant group, mothers and youth reported similar rates of symptoms of mania. There were no differences between the concordant and discordant groups in onset, duration, or impairment of mania, rates of psychiatric hospitalization, cognitive variables, or rates of disorders in family members. The similarities between discordant and concordant reports in symptomatology of mania and depression, rates of comorbidities, treatment needs, and other clinical correlates suggest that a mother-based diagnosis of mania should not be discounted in discrepant cases in which the youth fails to endorse the diagnosis. C1 [Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat Neurosci & Physiol, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Pediat Psychopharmacol Unit, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU National Institute of Mental Health [R01MH066237]; National Institute on Drug Abuse [R01DA12945] FX This study was supported by National Institute of Mental Health grant R01MH066237 (JW) and National Institute on Drug Abuse grant R01DA12945 (TEW). NR 19 TC 4 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAY PY 2009 VL 11 IS 3 BP 298 EP 306 DI 10.1111/j.1399-5618.2009.00671.x PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 433DR UT WOS:000265185000006 PM 19419387 ER PT J AU Owen, MH Roecklein-Canfield, J Qu, QQA Leung, W Ahsan, S Shea, C Holmes, LB AF Owen, M. H. Roecklein-Canfield, J. Qu, Q-Q A. Leung, W. Ahsan, S. Shea, C. Holmes, L. B. TI Effects of Dominant hemimelia on Axial and Appendicular Patterning SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Owen, M. H.; Qu, Q-Q A.; Leung, W.; Ahsan, S.; Shea, C.] Simmons Coll, Dept Biol, Boston, MA 02115 USA. [Roecklein-Canfield, J.] Simmons Coll, Dept Chem, Boston, MA 02115 USA. [Owen, M. H.; Holmes, L. B.] MassGen Hosp Children, Genet Unit, Boston, MA USA. [Holmes, L. B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2009 VL 85 IS 5 BP 451 EP 451 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 454PX UT WOS:000266695900143 ER PT J AU Gardiner, DM Holmes, LB AF Gardiner, D. M. Holmes, L. B. TI Transverse Limb Deficiencies with Nubbins Represent Partial Limb Regeneration in Humans: An Hypothesis SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Gardiner, D. M.] Univ Calif Irvine, Irvine, CA USA. [Holmes, L. B.] MassGen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2009 VL 85 IS 5 BP 455 EP 455 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 454PX UT WOS:000266695900152 ER PT J AU Holmes, LB Smith, CR Shen, A Mittendorf, R Hernandez-Diaz, S AF Holmes, L. B. Smith, C. R. Shen, A. Mittendorf, R. Hernandez-Diaz, S. TI Comparative Safety of Some Anticonvulsant Polytherapies during Pregnancy SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Holmes, L. B.; Smith, C. R.; Shen, A.] MassGen Hosp Children, Boston, MA USA. [Hernandez-Diaz, S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mittendorf, R.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2009 VL 85 IS 5 BP 465 EP 465 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 454PX UT WOS:000266695900169 ER PT J AU Dahl, DM AF Dahl, Douglas M. TI The impact of training on service provision in laparoscopic radical prostatectomy COMMENT SO BJU INTERNATIONAL LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Dahl, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD MAY PY 2009 VL 103 IS 9 BP 1234 EP 1235 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 436OS UT WOS:000265424300018 ER PT J AU Van den Stock, J Peretz, I Grezes, J de Gelder, B AF Van den Stock, Jan Peretz, Isabelle Grezes, Julie de Gelder, Beatrice TI Instrumental Music Influences Recognition of Emotional Body Language SO BRAIN TOPOGRAPHY LA English DT Article DE Multisensory; Emotion; Body language; Music ID ACTION REPRESENTATION; VOICE; FEAR; EXPRESSIONS; PERCEPTION; AMYGDALA; NEURONS; MIRROR; SOUNDS; FACE AB In everyday life, emotional events are perceived by multiple sensory systems. Research has shown that recognition of emotions in one modality is biased towards the emotion expressed in a simultaneously presented but task irrelevant modality. In the present study, we combine visual and auditory stimuli that convey similar affective meaning but have a low probability of co-occurrence in everyday life. Dynamic face-blurred whole body expressions of a person grasping an object while expressing happiness or sadness are presented in combination with fragments of happy or sad instrumental classical music. Participants were instructed to categorize the emotion expressed by the visual stimulus. The results show that recognition of body language is influenced by the auditory stimuli. These findings indicate that crossmodal influences as previously observed for audiovisual speech can also be obtained from the ignored auditory to the attended visual modality in audiovisual stimuli that consist of whole bodies and music. C1 [de Gelder, Beatrice] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [de Gelder, Beatrice] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Van den Stock, Jan; de Gelder, Beatrice] Tilburg Univ, Lab Cognit & Affect Neurosci, NL-5000 LE Tilburg, Netherlands. [Van den Stock, Jan] Katholieke Univ Leuven Hosp, Dept Old Age Psychiat, B-3000 Louvain, Belgium. [Peretz, Isabelle] Univ Montreal, BRAMS, Dept Psychol, Outremont, PQ, Canada. [Grezes, Julie] Ecole Normale Super, INSERM, U742, Cognit Neurosci Lab, F-75231 Paris, France. [Grezes, Julie] Ecole Normale Super, DEC, F-75231 Paris, France. RP de Gelder, B (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Room 417,Bldg 36,1st St, Charlestown, MA 02129 USA. EM degelder@nmr.mgh.harvard.edu RI Van den Stock, Jan/F-1906-2014; Grezes, Julie/E-5060-2016 OI Van den Stock, Jan/0000-0001-5756-3195; NR 22 TC 20 Z9 20 U1 0 U2 12 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0896-0267 J9 BRAIN TOPOGR JI Brain Topogr. PD MAY PY 2009 VL 21 IS 3-4 BP 216 EP 220 DI 10.1007/s10548-009-0099-0 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 468NL UT WOS:000267826200009 PM 19588251 ER PT J AU Bafford, AC Burstein, HJ Barkley, CR Smith, BL Lipsitz, S Iglehart, JD Winer, EP Golshan, M AF Bafford, Andrea C. Burstein, Harold J. Barkley, Christina R. Smith, Barbara L. Lipsitz, Stuart Iglehart, James D. Winer, Eric P. Golshan, Mehra TI Breast surgery in stage IV breast cancer: impact of staging and patient selection on overall survival SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Review DE Stage IV breast cancer; Surgery; Survival; Mastectomy ID PRIMARY TUMOR; CHEMOTHERAPY; RESECTION; THERAPY AB Purpose Retrospective analyses suggest patients with stage IV breast cancer who undergo breast surgery have improved survival. We sought to determine whether surgery and other clinical and staging factors affected overall survival. Methods We performed a review of our prospectively maintained database of patients who presented with stage IV breast cancer between 1998 and 2005. We compared survival between women who received therapeutic surgery to the breast (S) versus those who did not (NS). Results Of the 147 women who presented with stage IV breast carcinoma, 61 (41%) underwent mastectomy or lumpectomy. Median overall survival unadjusted was 3.52 years for S versus 2.36 years for NS (P = 0.093). ER and Her2neu status were positive predictors of survival (HR: 0.191 and 0.285 P < 0.0001); CNS and liver metastases were adverse predictors (HR: 2.05 and 1.59 P = 0.015 P = 0.059). On multivariate survival was significantly superior in the surgery group (HR: 0.47 P = 0.003 mean 4.13 years versus 2.36 years). In those undergoing surgery, 36 women were diagnosed with metastatic disease postoperatively and 25 preoperatively. These groups had median survival of 4.0 years and 2.4 years, respectively, comparable to those in the NS group (2.36 years, (P = 0.18). Conclusions Breast surgery is associated with improved survival in stage IV breast cancer. However, in our experience, this benefit is only realized among patients operated on before diagnosis of metastatic disease and is likely a consequence of stage migration bias. While some women may warrant palliative surgery to the breast, it is unclear that such surgery otherwise improves clinical outcomes. C1 [Bafford, Andrea C.; Burstein, Harold J.; Barkley, Christina R.; Lipsitz, Stuart; Iglehart, James D.; Golshan, Mehra] Brigham & Womens Hosp, Boston, MA 02115 USA. [Burstein, Harold J.; Iglehart, James D.; Winer, Eric P.; Golshan, Mehra] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, Barbara L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 14 TC 60 Z9 62 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 MAY PY 2009 VL 115 IS 1 BP 7 EP 12 DI 10.1007/s10549-008-0101-7 PG 6 WC Oncology SC Oncology GA 436UA UT WOS:000265440400002 PM 18581232 ER PT J AU Dickler, MN Cobleigh, MA Miller, KD Klein, PM Winer, EP AF Dickler, Maura N. Cobleigh, Melody A. Miller, Kathy D. Klein, Pamela M. Winer, Eric P. TI Efficacy and safety of erlotinib in patients with locally advanced or metastatic breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Epidermal growth factor receptor (EGFR/HER1); Erlotinib; Metastatic breast cancer; Patient selection ID GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; PHASE-II; COLORECTAL-CANCER; ADJUVANT CHEMOTHERAPY; SOLID TUMORS; GEFITINIB; PLUS; TRIAL AB Purpose To evaluate the efficacy and safety of erlotinib in advanced breast cancer. Experimental design Multicenter, phase II study of erlotinib (150 mg orally daily). Cohort 1: progression after anthracyclines, taxanes, and capecitabine (n = 47). Cohort 2: progression after > 1 chemotherapy for advanced-stage disease (n = 22). Primary endpoint was response rate (World Health Organization criteria). Secondary endpoints were safety, time to progression, and survival. Results One patient in each cohort (n = 2, 3.0%) had a partial response. Response duration was 17 weeks for the Cohort 1 patient and 32 weeks for the Cohort 2 patient. Median time to progression was 43 days for Cohort 1 (range 1-204) and 43 days for Cohort 2 (range 25-419). Common adverse events were diarrhea, rash, dry skin, asthenia, nausea, anorexia. Conclusion Erlotinib had minimal activity in unselected previously treated women with advanced breast cancer. Predictive factors are needed to identify breast cancer patients who may derive benefit from erlotinib treatment. C1 [Dickler, Maura N.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Cobleigh, Melody A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Miller, Kathy D.] Indiana Canc Pavill, Indianapolis, IN 46202 USA. [Klein, Pamela M.] Genentech Inc, San Francisco, CA 94080 USA. [Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dickler, MN (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM dicklerm@mskcc.org NR 40 TC 60 Z9 60 U1 0 U2 2 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 MAY PY 2009 VL 115 IS 1 BP 115 EP 121 DI 10.1007/s10549-008-0055-9 PG 7 WC Oncology SC Oncology GA 436UA UT WOS:000265440400012 PM 18496750 ER PT J AU Partridge, AH Wolff, AC Marcom, PK Kaufman, PA Zhang, L Gelman, R Moore, C Lake, D Fleming, GF Rugo, HS Atkins, J Sampson, E Collyar, D Winer, EP AF Partridge, Ann H. Wolff, A. C. Marcom, P. K. Kaufman, P. A. Zhang, L. Gelman, R. Moore, C. Lake, D. Fleming, G. F. Rugo, H. S. Atkins, J. Sampson, E. Collyar, D. Winer, E. P. TI The impact of sharing results of a randomized breast cancer clinical trial with study participants SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Clinical trial results; Cancer communication; Research ethics; Adjuvant trastuzumab ID INFORMED-CONSENT; PREFERENCES; WOMEN AB Background There has been growing interest in providing clinical trial participants with study results yet only limited information exists regarding the process and impact of sharing results. We sought to evaluate patient perceptions of how results had been shared from a large randomized cooperative group trial, and the impact of learning results. Patients and methods A subset of women who participated in NCCTG 9831 (A Phase III Trial of Adjuvant Chemotherapy with or without Trastuzumab for Women with HER2-positive Breast Cancer) were mailed surveys after the preliminary study results were released to the public and mailed to participants. Results One hundred and 67 of 228 surveys sent (73%) were returned; 61% reported receiving trastuzumab on study; 4% reported recurrent disease. Ninety-five percent of participants were glad they received results; 81% were satisfied with how results were shared; 23% were more anxious after learning the results. Sixty-nine percent correctly interpreted the results. Logistic regression revealed that satisfaction with the process of receiving results was associated with satisfaction with treatment (P = 0.04), and increased anxiety was associated with dissatisfaction with treatment (0.02), incorrect interpretation of results (0.04), and not having received trastuzumab (P < 0.0001). Conclusion Sharing results directly with study participants is met with overwhelmingly favorable responses from patients, although some may not initially understand the findings. The potential for increased anxiety should be considered, and psychosocial support may be required by some. A plan to share results should be routinely and prospectively considered in the design of cancer clinical trials. C1 [Partridge, Ann H.; Zhang, L.; Gelman, R.; Sampson, E.; Winer, E. P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolff, A. C.] Sidney Kimmel Canc Ctr Johns Hopkins, Baltimore, MD USA. [Marcom, P. K.] Duke Univ, Med Ctr, Durham, NC USA. [Kaufman, P. A.; Moore, C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Lake, D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Fleming, G. F.] Univ Chicago, Chicago, IL 60637 USA. [Rugo, H. S.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Atkins, J.] SE Med Oncol Ctr, Goldsboro, NC USA. [Collyar, D.] Canc & Leukemia Grp B & Patient Advocates Res, Danville, PA USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ahpartridge@partners.org OI Wolff, Antonio/0000-0003-3734-1063 FU NCI NIH HHS [U10 CA032291] NR 28 TC 13 Z9 13 U1 1 U2 2 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 MAY PY 2009 VL 115 IS 1 BP 123 EP 129 DI 10.1007/s10549-008-0057-7 PG 7 WC Oncology SC Oncology GA 436UA UT WOS:000265440400013 PM 18543100 ER PT J AU Pappalardo, F Halling-Brown, MD Rapin, N Zhang, P Alemani, D Emerson, A Paci, P Duroux, P Pennisi, M Palladini, A Miotto, O Churchill, D Rossi, E Shepherd, AJ Moss, DS Castiglione, F Bernaschi, M Lefranc, MP Brunak, S Motta, S Lollini, PL Basford, KE Brusic, V AF Pappalardo, Francesco Halling-Brown, Mark D. Rapin, Nicolas Zhang, Ping Alemani, Davide Emerson, Andrew Paci, Paola Duroux, Patrice Pennisi, Marzio Palladini, Arianna Miotto, Olivo Churchill, Daniel Rossi, Elda Shepherd, Adrian J. Moss, David S. Castiglione, Filippo Bernaschi, Massimo Lefranc, Marie-Paule Brunak, Soren Motta, Santo Lollini, Pier-Luigi Basford, Kaye E. Brusic, Vladimir TI ImmunoGrid, an integrative environment for large-scale simulation of the immune system for vaccine discovery, design and optimization SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE computational modeling; Grid computing; immunoinformatics; simulations; vaccine discovery ID MHC CLASS-I; PREDICTING PEPTIDES BINDING; T-CELL EPITOPES; PROTEASOMAL CLEAVAGE; IMGT-ONTOLOGY; MOLECULES; RESOURCE; DATABASE; TARGETS; MODELS AB Vaccine research is a combinatorial science requiring computational analysis of vaccine components, formulations and optimization. We have developed a framework that combines computational tools for the study of immune function and vaccine development. This framework, named ImmunoGrid combines conceptual models of the immune system, models of antigen processing and presentation, system-level models of the immune system, Grid computing, and database technology to facilitate discovery, formulation and optimization of vaccines. ImmunoGrid modules share common conceptual models and ontologies. The ImmunoGrid portal offers access to educational simulators where previously defined cases can be displayed, and to research simulators that allow the development of new, or tuning of existing, computational models. The portal is accessible at http://www.w3.org. C1 [Zhang, Ping] Univ Queensland, Diamantina Inst Canc Immunol & Metab Med, Brisbane, Qld 4072, Australia. [Paci, Paola] CNR, Inst Comp Applicat, Rome, Italy. [Churchill, Daniel] Univ Hong Kong, Fac Educ, Div Informat & Technol Studies, Hong Kong, Hong Kong, Peoples R China. [Moss, David S.] Sch Crystallog Birkbeck, Birkbeck, England. [Bernaschi, Massimo] Univ Roma La Sapienza, Rome, Italy. [Lefranc, Marie-Paule] Univ Montpellier 2, F-34095 Montpellier 5, France. [Lefranc, Marie-Paule] CNRS, IGM, Inst Human Genet, Immunogenet Mol Lab, F-75700 Paris, France. [Brunak, Soren] Univ Copenhagen, Ctr Prot Res, Novo Nordisk Fdn, DK-1168 Copenhagen, Denmark. [Brunak, Soren] Tech Univ Denmark, Dept Syst Biol, Lyngby, Denmark. [Motta, Santo] Univ Catania, Fac Pharm, I-95124 Catania, Italy. [Lollini, Pier-Luigi] Univ Bologna, I-40126 Bologna, Italy. [Basford, Kaye E.] Univ Queensland, Sch Land Crop & Food Sci, Brisbane, Qld 4072, Australia. [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Brusic, V (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vladimir_brusic@dfci.harvard.edu RI Churchill, Daniel/C-7693-2009; Zhang, Ping/E-5306-2010; Basford, Kaye/G-5837-2010; Alemani, Davide/A-6102-2011; Palladini, Arianna/A-8994-2013; Pappalardo, Francesco/C-5832-2011; Castiglione, Filippo/B-1366-2010; Pennisi, Marzio/G-4618-2015; OI Lollini, Pier Luigi/0000-0003-1702-4108; Motta, Santo/0000-0003-3533-2972; Pappalardo, Francesco/0000-0003-1668-3320; Castiglione, Filippo/0000-0002-1442-3552; Pennisi, Marzio/0000-0003-0231-7653; Rapin, Nicolas/0000-0001-5208-8874; Miotto, Olivo/0000-0001-8060-6771 FU EC [FP6-2004-IST-4, 028069]; Associazione Italiana per la Ricerca sul Cancro FX The ImmunoGrid project has been funded by the EC contract FP6-2004-IST-4, No. 028069. NR 84 TC 28 Z9 29 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD MAY PY 2009 VL 10 IS 3 BP 330 EP 340 DI 10.1093/bib/bbp014 PG 11 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 437YG UT WOS:000265522200011 PM 19383844 ER PT J AU Yetgin, S Ozbek, NY Masera, G Valsecchi, MG Dacou-Voutetakis Loening, L Schrappe, M Zimmermann, M Henze, G von Stackelberg, A Gadner, H Mann, G Attarbaschi, A Brandalise, SR Carroll, WL Gaynon, P Boyett, JM Nachman, J Devidas, M Sather, HN Escherich, G Janka, G Gelber, RD Sallan, SE Pieters, R Bierings, M Kamps, WA Otten, J Suciu, S Viana, MB Baruchel, A Auclerc, M Perez, C Solidaro, A Stark, B Steinberg, D Koizumi, S Tsurusawa, M Zintl, F Schiller, I Matsuzaki, A Eden, TOB Lilleyman, JS Richards, S Steinherz, PG Steinherz, L Kochupillai, V Bakhshi, S Ortega, JJ Nachman, J Appelbaum, FR Cheng, C Pei, D Pui, CH Kukure, P Nakazawa, S Tsuchida, M Elphinstone, T Evans, V Gettins, L Hicks, C MacKinnon, L Morris, P Richards, S Wade, R AF Yetgin, S. Oezbek, N. Y. Masera, G. Valsecchi, M. G. Dacou-Voutetakis Loening, L. Schrappe, M. Zimmermann, M. Henze, G. von Stackelberg, A. Gadner, H. Mann, G. Attarbaschi, A. Brandalise, S. R. Carroll, W. L. Gaynon, P. Boyett, J. M. Nachman, J. Devidas, M. Sather, H. N. Escherich, G. Janka, G. Gelber, R. D. Sallan, S. E. Pieters, R. Bierings, M. Kamps, W. A. Otten, J. Suciu, S. Viana, M. B. Baruchel, A. Auclerc, M. Perez, C. Solidaro, A. Stark, B. Steinberg, D. Koizumi, S. Tsurusawa, M. Zintl, F. Schiller, I. Matsuzaki, A. Eden, T. O. B. Lilleyman, J. S. Richards, S. Steinherz, P. G. Steinherz, L. Kochupillai, V. Bakhshi, S. Ortega, J. J. Nachman, J. Appelbaum, F. R. Cheng, C. Pei, D. Pui, C. H. Kukure, P. Nakazawa, S. Tsuchida, M. Elphinstone, T. Evans, V. Gettins, L. Hicks, C. MacKinnon, L. Morris, P. Richards, S. Wade, R. CA Childhood Acute Lymphoblastic Leuk TI Beneficial and harmful effects of anthracyclines in the treatment of childhood acute lymphoblastic leukaemia: a systematic review and meta-analysis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE anthracycline; leukaemia; childhood ALL; meta-analysis; randomized ID CLINICAL HEART-FAILURE; LIPOSOME-ENCAPSULATED DOXORUBICIN; ACUTE LYMPHOCYTIC-LEUKEMIA; TERM-FOLLOW-UP; CONVENTIONAL DOXORUBICIN; MULTICENTER TRIAL; INDUCTION THERAPY; RISK-FACTORS; CHILDREN; CARDIOTOXICITY AB Anthracyclines are used to treat childhood acute lymphoblastic leukaemia (ALL) but non-randomized studies suggest that cardiotoxicity may be a problem. Individual patient data from trials in childhood ALL that randomized anthracyclines or methods of reducing cardiotoxicity were analysed by standard meta-analysis methods. Results were grouped and combined according to: addition of an anthracycline to standard therapy, type of anthracycline, mode of administration, and the use of a cardioprotectant. Data from 958 patients in 4 trials, recruiting between 1972 and 1984, showed that addition of an anthracycline reduced bone marrow relapse and, non-significantly, non-bone marrow relapse, resulting in an increased relapse-free interval. However there was a non-significant increase in induction failures, and in deaths in first remission. Event-free survival at 5 years was 56.7% with anthracycline versus 52.8% without (Odds Ratio = 0.91; 95% Confidence Interval = 0.76-1.10; P = 0.3). There were no significant differences found in other treatment comparisons. The limited data from trials did not demonstrate differences in clinically evident cardiotoxicity. Anthracyclines are effective against bone marrow relapse but have not been shown to significantly increase event free survival in childhood ALL. The evidence on type of anthracycline, method of administration or use of cardioprotectant was insufficient to be able to rule out important differences. C1 [Loening, L.; Schrappe, M.; Zimmermann, M.; Henze, G.; von Stackelberg, A.] Berlin Frankfurt Muenster BFM, Berlin, Germany. [Gelber, R. D.; Sallan, S. E.] Dana Farber Canc Inst, Boston, MA USA. [Viana, M. B.] Univ Fed Minas Gerais, Fac Med, Belo Horizonte, MG, Brazil. [Zintl, F.; Schiller, I.] Univ Jena, D-6900 Jena, Germany. [Eden, T. O. B.; Lilleyman, J. S.; Richards, S.] MRC, London W1N 4AL, England. [Steinherz, P. G.; Steinherz, L.] Mem & Sloan Kettering Canc Ctr, New York, NY USA. [Cheng, C.; Pei, D.; Pui, C. H.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Kukure, P.] Tata Mem Hosp, Bombay 400012, Maharashtra, India. [Nakazawa, S.; Tsuchida, M.] Tokyo Childrens Canc Study Grp, Tokyo, Japan. [Childhood Acute Lymphoblastic Leuk] Univ Oxford, CALLCG Secretariat, Oxford OX3 7LF, England. RI Schrappe, Martin/A-8109-2010; Viana, Marcos/E-8415-2010 OI Viana, Marcos/0000-0001-9665-2115 FU Kay Kendall Leukaemia Fund [KKL293]; Cancer Research UK; Medical Research Council FX The secretariat for this work was at CTSU, Oxford University. The work was funded by a grant from the Kay Kendall Leukaemia Fund (KKL293) with additional support from Cancer Research UK and Medical Research Council. Funders were not involved in the design, analysis or reporting. NR 28 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2009 VL 145 IS 3 BP 376 EP 388 DI 10.1111/j.1365-2141.2009.07624.x PG 13 WC Hematology SC Hematology GA 430SP UT WOS:000265009100012 ER PT J AU Clegg, LX Reichman, ME Miller, BA Hankey, BF Singh, GK Lin, YD Goodman, MT Lynch, CF Schwartz, SM Chen, VW Bernstein, L Gomez, SL Graff, JJ Lin, CC Johnson, NJ Edwards, BK AF Clegg, Limin X. Reichman, Marsha E. Miller, Barry A. Hankey, Benjamin F. Singh, Gopal K. Lin, Yi Dan Goodman, Marc T. Lynch, Charles F. Schwartz, Stephen M. Chen, Vivien W. Bernstein, Leslie Gomez, Scarlett L. Graff, John J. Lin, Charles C. Johnson, Norman J. Edwards, Brenda K. TI Impact of socioeconomic status on cancer incidence and stage at diagnosis: selected findings from the surveillance, epidemiology, and end results: National Longitudinal Mortality Study SO CANCER CAUSES & CONTROL LA English DT Article DE SEER; NLMS; Cancer incidence; Stage; Education; Income; Poverty; Unemployment; SES; Race/ethnicity; Rural/urban; Health disparities; Record linkage ID BREAST-CANCER; UNITED-STATES; CERVICAL-CANCER; SOCIAL-CLASS; RACIAL-DIFFERENCES; COLORECTAL-CANCER; PROSTATE-CANCER; RESULTS PROGRAM; DEATH INDEX; US WOMEN AB Population-based cancer registry data from the Surveillance, Epidemiology, and End Results (SEER) Program at the National Cancer Institute (NCI) are mainly based on medical records and administrative information. Individual-level socioeconomic data are not routinely reported by cancer registries in the United States because they are not available in patient hospital records. The U.S. representative National Longitudinal Mortality Study (NLMS) data provide self-reported, detailed demographic and socioeconomic data from the Social and Economic Supplement to the Census Bureau's Current Population Survey (CPS). In 1999, the NCI initiated the SEER-NLMS study, linking the population-based SEER cancer registry data to NLMS data. The SEER-NLMS data provide a new unique research resource that is valuable for health disparity research on cancer burden. We describe the design, methods, and limitations of this data set. We also present findings on cancer-related health disparities according to individual-level socioeconomic status (SES) and demographic characteristics for all cancers combined and for cancers of the lung, breast, prostate, cervix, and melanoma. Records of cancer patients diagnosed in 1973-2001 when residing 1 of 11 SEER registries were linked with 26 NLMS cohorts. The total number of SEER matched cancer patients that were also members of an NLMS cohort was 26,844. Of these 26,844 matched patients, 11,464 were included in the incidence analyses and 15,357 in the late-stage diagnosis analyses. Matched patients (used in the incidence analyses) and unmatched patients were compared by age group, sex, race, ethnicity, residence area, year of diagnosis, and cancer anatomic site. Cohort-based age-adjusted cancer incidence rates were computed. The impact of socioeconomic status on cancer incidence and stage of diagnosis was evaluated. Men and women with less than a high school education had elevated lung cancer rate ratios of 3.01 and 2.02, respectively, relative to their college educated counterparts. Those with family annual incomes less than $12,500 had incidence rates that were more than 1.7 times the lung cancer incidence rate of those with incomes $50,000 or higher. Lower income was also associated with a statistically significantly increased risk of distant-stage breast cancer among women and distant-stage prostate cancer among men. Socioeconomic patterns in incidence varied for specific cancers, while such patterns for stage were generally consistent across cancers, with late-stage diagnoses being associated with lower SES. These findings illustrate the potential for analyzing disparities in cancer outcomes according to a variety of individual-level socioeconomic, demographic, and health care characteristics, as well as by area measures available in the linked database. C1 [Clegg, Limin X.] US Dept Vet Affairs, Off Healthcare Inspect, Off Inspector Gen, Washington, DC 20420 USA. [Reichman, Marsha E.; Miller, Barry A.; Edwards, Brenda K.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Hankey, Benjamin F.] Informat Management Serv Inc, Silver Spring, MD USA. [Singh, Gopal K.] US Hlth Resources & Serv Adm, Rockville, MD 20857 USA. [Lin, Yi Dan] Monash Univ, Sch Med, Melbourne, Vic 3004, Australia. [Goodman, Marc T.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Lynch, Charles F.] Univ Iowa, State Hlth Registry Iowa, Iowa City, IA USA. [Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Chen, Vivien W.] LSU Sch Publ Hlth, Louisiana Tumor Registry, New Orleans, LA USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA. [Gomez, Scarlett L.] No Calif Canc Ctr, Fremont, CA USA. [Graff, John J.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Lin, Charles C.; Johnson, Norman J.] US Bur Census, Suitland, MD USA. RP Clegg, LX (reprint author), US Dept Vet Affairs, Off Healthcare Inspect, Off Inspector Gen, 54AA,810 Vermont Ave NW, Washington, DC 20420 USA. EM Lin.Clegg@va.gov FU National Cancer Institute FX We thank Marie-Josephe Horner, epidemiologist from the National Cancer Institute, for technical and editorial assistance in the preparation of this manuscript. NR 52 TC 238 Z9 239 U1 8 U2 55 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2009 VL 20 IS 4 BP 417 EP 435 DI 10.1007/s10552-008-9256-0 PG 19 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 430VV UT WOS:000265018900002 PM 19002764 ER PT J AU Bowen, DJ Sorensen, G Weiner, BJ Campbell, M Emmons, K Melvin, C AF Bowen, Deborah J. Sorensen, Glorian Weiner, Bryan J. Campbell, Marci Emmons, Karen Melvin, Cathy TI Dissemination research in cancer control: where are we and where should we go? SO CANCER CAUSES & CONTROL LA English DT Review DE Dissemination; Implementation; Diffusion; Translation ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-PROMOTION RESEARCH; PUBLIC-HEALTH; PHYSICAL-ACTIVITY; QUALITY IMPROVEMENT; EXTERNAL VALIDITY; BEHAVIOR-CHANGE; INTERVENTIONS; COMMUNITY; IMPLEMENTATION AB Dissemination of evidence-based programs and policies is a critical final step in reducing the burden of cancer in the general public. Yet, we have not been fully successful to date in improving clinical or public health practice by disseminating programs found to be effective in research. Therefore, research is needed into the dissemination process and outcomes to enable better efforts in the future. This paper explores the definitions and models used for dissemination, the designs of dissemination studies, and possible research questions in dissemination research, all focused on cancer prevention and control. We hope that this paper will encourage dissemination research in our field. C1 [Bowen, Deborah J.] Boston Univ, Sch Publ Hlth, Social & Behav Sci Dept, Boston, MA 02118 USA. [Sorensen, Glorian; Emmons, Karen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sorensen, Glorian; Emmons, Karen] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Weiner, Bryan J.] Univ N Carolina, Sch Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Campbell, Marci] Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. [Campbell, Marci] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Melvin, Cathy] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. RP Bowen, DJ (reprint author), Boston Univ, Sch Publ Hlth, Social & Behav Sci Dept, 715 Albany St,T2 W, Boston, MA 02118 USA. EM dbowen@bu.edu FU Liberty Mutual [DP00059-04, CA124400]; [DK56350]; [CA124415]; [CA11464]; [CA124394]; [CA108663]; [DP000064] FX We gratefully acknowledge the support from the following grants: DK56350, CA124415, CA11464, CA124394, CA108663, DP000064, a grant from Liberty Mutual, DP00059-04, and CA124400 in completing this work. NR 69 TC 28 Z9 28 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2009 VL 20 IS 4 BP 473 EP 485 DI 10.1007/s10552-009-9308-0 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 430VV UT WOS:000265018900006 PM 19224380 ER PT J AU Duan, ZF Choy, E Jimeno, JM Cuevas, CDM Mankin, HJ Hornicek, FJ AF Duan, Zhenfeng Choy, Edwin Jimeno, Jose Maria Cuevas, Carmen Del Maria Mankin, Henry J. Hornicek, Francis J. TI Diverse cross-resistance phenotype to ET-743 and PM00104 in multi-drug resistant cell lines SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE ET-743; Yondelis; PM00104; Zalypsis; ABCB1/MDR1; Multi-drug resistance gene 1 ID SOFT-TISSUE SARCOMAS; DNA-REPAIR PATHWAYS; OVARIAN-CANCER; PHASE-II; ECTEINASCIDIN-743 ET-743; ANTICANCER AGENTS; DRUG-RESISTANCE; TRABECTEDIN; EXPRESSION; GENES AB Purpose ET-743 (Yondelis (R), trabectedin) and PM00104 (Zalypsis (R)) are marine derived compounds which demonstrate anti-tumor activity. The present study was performed to elucidate the relationship between the expression of ABCB1/MDR1 and ABCC1/MRP1 with resistance to either ET-743 or PM00104. Methods We evaluate the association between expression of Pgp1, MRP1, and BCRP proteins and ET-743 or PM00104 resistance in a large panel of multi-drug resistant cell lines derived from histologically unrelated human tumors that were selected with paclitaxel, doxorubicin, cisplatin, mitoxantrane, or gemcitibine. Results Paclitaxel selected resistantcell lines expressed high levels of ABCB1 (but not ABCC1 or ABCG2/BCRP) did not demonstrate cross-resistance to either ET-743 or PM00104. In contrast, the doxorubicin selected resistant cell lines also expressed high level of ABCB1 (but not ABCC1 or ABCG2) but did demonstrate significant cross-resistance to both ET-743 and PM00104. The paclitaxel selected cell lines demonstrated cross-resistance to doxorubicin, vincristine, and mitoxantrane, while most of the above doxorubicin selected cell lines demonstrated cross-resistance to paclitaxel and vincristine, but not to mitoxantrane. On the contrary, cisplatin and gemcitabine selected cell lines demonstrated no cross-resistance to paclitaxel, doxorubicin, ET-743, or PM00104. siRNA down-regulation of ABCB1 expression in doxorubicin selected cell lines caused partial sensitization to both doxorubicin and paclitaxel but not to either ET-743 or PM00104. Conclusions These results indicate that cell lines selected for resistance to either paclitaxel or doxorubicin are cross-resistant to many other drugs and that, for these cell lines, ABCB1 over-expression is not necessary to confer resistance to either ET-743 or PM00104. Diversity of cross-resistance observed in these multi-drug resistant cell lines are associated with the initial drug used for in vitro selection, but not to ABCB1 expression. This study suggests that a common molecular pathway other than ABCB1 may be involved in the mechanism of resistance to ET-743 or PM00104. C1 [Duan, Zhenfeng; Mankin, Henry J.; Hornicek, Francis J.] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Choy, Edwin] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Jimeno, Jose Maria; Cuevas, Carmen Del Maria] PharmaMar USA Inc, Cambridge, MA 02142 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, 100 Blossom St Jackson 1106, Boston, MA 02114 USA. EM zduan@partners.org OI Choy, Edwin/0000-0001-9896-8084 FU PharmaMar; Ovarian Cancer Research Foundation (OCRF); National Cancer Institute, NIH (Nanotechnology Platform Partnership) [R01-CA119617]; Gaetagno and Wechsler funds FX This project was supported by a Grant from PharmaMar. Dr. Duan is supported, in part, through a grant from Ovarian Cancer Research Foundation (OCRF), and a grant from the National Cancer Institute, NIH (Nanotechnology Platform Partnership), R01-CA119617. Support has also been provided by the Gaetagno and Wechsler funds. NR 28 TC 12 Z9 12 U1 2 U2 7 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 MAY PY 2009 VL 63 IS 6 BP 1121 EP 1129 DI 10.1007/s00280-008-0843-2 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 434EF UT WOS:000265257300016 PM 18828019 ER PT J AU Ibarra-Drendall, C Wilke, LG Zalles, C Scott, V Archer, LE Lem, S Yee, LD Lester, J Kulkarni, S Murekeyisoni, C Wood, M Wilson, K Garber, J Gentry, C Stouder, A Broadwater, G Baker, JC Vasilatos, SN Owens, E Rabiner, S Barron, AC Seewaldt, VL AF Ibarra-Drendall, Catherine Wilke, Lee G. Zalles, Carola Scott, Victoria Archer, Laura E. Lem, Siya Yee, Lisa D. Lester, Joanne Kulkarni, Swati Murekeyisoni, Christine Wood, Marie Wilson, Karen Garber, Judy Gentry, Carleen Stouder, April Broadwater, Gloria Baker, Joseph C., Jr. Vasilatos, Shauna N. Owens, Elizabeth Rabiner, Sarah Barron, Abbey C. Seewaldt, Victoria L. TI Reproducibility of Random Periareolar Fine Needle Aspiration in a Multi-institutional Cancer and Leukemia Group B (CALGB) Cross-Sectional Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GROWTH-FACTOR-I; BREAST-CANCER; HIGH-RISK; WOMEN; CHEMOPREVENTION; TAMOXIFEN; PROMOTER; ATYPIA; HYPERMETHYLATION; METHYLATION AB Background: Random periareolar fine needle aspiration (RPFNA) is a research technique developed to assess short-term breast cancer risk in women at increased risk of breast cancer. Although there is increasing acceptance of RPFNA, neither the reproducibility nor the inter-institutional compatibility of RPFNA has been established. To address these key limitations, the Cancer and Leukemia Group B (CALGB) Prevention Group tested the reproducibility of RPFNA in a multi-institutional cross-sectional study. Methods: Sixty-three high-risk women from five CALGB institutions (Duke, Ohio State, Roswell Park, Dana Farber, and Vermont) underwent RPFNA from July 1, 2007 to June 30, 2008. Duplicate bilateral RPFNA was performed on each woman by a single investigator on a single day. Masood Cytology Index score was assessed by a single blinded cytopathologist. Results: There was a high degree of statistical agreement in the Masood Cytology Index scores of duplicate RPFNA samples from the same breast, with a Spearman correlation coefficient of 0.8312 (P < 0.0001). Importantly, although there was agreement in duplicate samples from the same breast, there was lack of agreement between duplicate samples from the opposite breast. Conclusions: This multi-institutional study shows that RPFNA is a highly reproducible measure of breast cytology in a cooperative group cross-sectional trial. RPFNA did not show a high degree of agreement between breasts, suggesting that breast cancer risk and progression may occur at different rates in individual breasts from a single woman. These studies provide proof-of-principle for future RPFNA-based cooperative group prevention studies. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1379-85) C1 [Ibarra-Drendall, Catherine; Wilke, Lee G.; Scott, Victoria; Archer, Laura E.; Lem, Siya; Stouder, April; Broadwater, Gloria; Baker, Joseph C., Jr.; Vasilatos, Shauna N.; Owens, Elizabeth; Rabiner, Sarah; Barron, Abbey C.; Seewaldt, Victoria L.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Zalles, Carola] Yale Univ, New Haven, CT USA. [Yee, Lisa D.; Lester, Joanne] Ohio State Univ, Columbus, OH 43210 USA. [Kulkarni, Swati; Murekeyisoni, Christine] SUNY Buffalo, Roswell Pk Canc Inst, Buffalo, NY 14260 USA. [Wood, Marie; Wilson, Karen] Univ Vermont, Burlington, VT USA. [Garber, Judy; Gentry, Carleen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Seewaldt, VL (reprint author), Duke Univ, Med Ctr, Box 2628, Durham, NC 27710 USA. EM seewa001@mc.duke.edu FU Cancer and Leukemia Group B (CALGB) pilot grant and parent grant [CA33601]; NIH/NCI [R01CA88799, R01CA98441, R01CA114068] FX Grant support: Primary Support as provided by the Cancer and Leukemia Group B (CALGB) pilot grant and parent grant CA33601 as well as NIH/NCI grants R01CA88799, R01CA98441, and R01CA114068 (V.L. Seewaldt). NR 29 TC 6 Z9 6 U1 2 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 MAY PY 2009 VL 18 IS 5 BP 1379 EP 1385 DI 10.1158/1055-9965.EPI-08-1210 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 445WF UT WOS:000266081500007 PM 19383884 ER PT J AU Satia, JA Littman, A Slatore, CG Galanko, JA White, E AF Satia, Jessie A. Littman, Alyson Slatore, Christopher G. Galanko, Joseph A. White, Emily TI Associations of Herbal and Specialty Supplements with Lung and Colorectal Cancer Risk in the VITamins And Lifestyle Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ALTERNATIVE MEDICINE USE; DIETARY-SUPPLEMENTS; UNITED-STATES; NATIONAL-SURVEY; GLUCOSAMINE; OSTEOARTHRITIS; COMPLEMENTARY; CHONDROITIN; PREVENTION; TRENDS AB Millions of Americans use dietary supplements with little knowledge about their benefits or risks. We examined associations of various herbal/specialty supplements with lung and colorectal cancer risk. Men and women, 50 to 76 years, in the VITamins And Lifestyle cohort completed a 24-page baseline questionnaire that captured duration (years) and frequency (days per week) of use of commonly used herbal/specialty supplements. Dose was not assessed due to the lack of accurate potency information. Supplement exposure was categorized as "no use" or "any use" over the previous 10 years. Hazard ratios (HR) were estimated by multivariate Cox regression models. Incident lung (n = 665) and colorectal cancers (n = 428) were obtained from the Surveillance, Epidemiology, and End Results cancer registry. Any use of glucosamine and chondroitin, which have anti-inflammatory properties, over the previous 10 years, was associated with significantly lower lung cancer risk: HR 0.74 [95% confidence interval (95% CI), 0.58-0.94] and HR 0.72 (95% CI, 0.54-0.96) and colorectal cancer risk: HR 0.73 (95% CI, 0.54-0.98) and HR 0.65 (95% CI, 0.45-0.93), respectively. There were also statistically significantly inverse associations of fish oil: HR 0.65 (95% CI, 0.42-0.99), methylsulfonylmethane: HR 0.46 (95% CI, 0.23-0.93), and St. John's wort: HR 0.35 (95% CI, 0.140.85) with colorectal cancer risk. In contrast, garlic pills were associated with a statistically significant 35% elevated colorectal cancer risk. These results suggest that some herbal/specialty supplements may be associated with lung and colorectal cancer risk; however, these products should be used with caution. Additional studies examining the effects of herbal/specialty supplements on risk for cancer and other diseases are needed. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1419-28) C1 [Satia, Jessie A.] Univ N Carolina, Dept Nutr, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Satia, Jessie A.] Univ N Carolina, Dept Epidemiol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Satia, Jessie A.] Univ N Carolina, Dept Epidemiol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Satia, Jessie A.; Galanko, Joseph A.] Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Div Digest Dis & Nutr, Chapel Hill, NC 27599 USA. [Littman, Alyson; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Littman, Alyson] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Slatore, Christopher G.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [White, Emily] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. RP Satia, JA (reprint author), Univ N Carolina, Dept Nutr, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM jsatia@unc.edu OI Slatore, Christopher/0000-0003-0958-8122 FU National Cancer Institute [R01 CA74846, K22CA096556, R03 CA 119683-01] FX Grant support: National Cancer Institute grants R01 CA74846, K22CA096556, and R03 CA 119683-01. NR 49 TC 32 Z9 33 U1 1 U2 3 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 MAY PY 2009 VL 18 IS 5 BP 1419 EP 1428 DI 10.1158/1055-9965.EPI-09-0038 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 445WF UT WOS:000266081500013 PM 19423520 ER PT J AU Wiklund, FE Adami, HO Zheng, SL Stattin, P Isaacs, WB Gronberg, H Xu, JF AF Wiklund, Fredrik E. Adami, Hans-Olov Zheng, Sigun L. Stattin, Par Isaacs, William B. Gronberg, Henrik Xu, Jianfeng TI Established Prostate Cancer Susceptibility Variants are not Associated with Disease Outcome SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; CHROMOSOME 8Q24; RISK LOCUS; AFRICAN-AMERICANS; SEQUENCE VARIANTS; BREAST-CANCER; CONFIRMATION AB Recent genome-wide association studies have been successful in identifying common sequence variants associated with prostate cancer risk; however, their importance in prostate cancer prognosis remains unknown. To assess confirmed prostate cancer susceptibility variants with prostate cancer prognosis, we genotyped 16 established susceptibility variants in a Swedish cohort of 2,875 prostate cancer cases, ascertained between 2001 and 2003, with complete follow-up regarding vital status through January 2008. Cox regression models, adjusted for age, clinical stage, pathologic grade, nodal or distant metastases, and diagnostic serum levels of prostate-specific antigen level, were used to assess association between risk variants and prostate cancer-specific survival. During follow-up, 626 men died, and of those, 440 had prostate cancer classified as their underlying cause of death. We found no association between any of the explored sequence variants and prostate cancer-specific mortality, either in exploring individual variants or in assessing the cumulative effect of all variants. We conclude that hitherto established prostate cancer susceptibility variants are not associated with the lethal potential of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1659-62) C1 [Wiklund, Fredrik E.; Adami, Hans-Olov; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Adami, Hans-Olov] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Adami, Hans-Olov] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Zheng, Sigun L.; Xu, Jianfeng] Wake Forest Univ, Ctr Human Genom, Winston Salem, NC 27109 USA. [Stattin, Par] Umea Univ, Dept Surg & Preoperat Sci, Umea, Sweden. [Isaacs, William B.] Johns Hopkins Univ, Dept Urol, Baltimore, MD USA. RP Wiklund, FE (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, POB 281, SE-17177 Stockholm, Sweden. EM Frederik.wiklund@ki.se FU Swedish Cancer Society; NCI [R01CA105055] FX Swedish Cancer Society (F. Wiklund, H. Gronberg,and H-O. Adami). This study was also partially supported by an NCI grant R01CA105055 (J. Xu). NR 25 TC 34 Z9 34 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 MAY PY 2009 VL 18 IS 5 BP 1659 EP 1662 DI 10.1158/1055-9965.EPI-08-1148 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 445WF UT WOS:000266081500044 PM 19423541 ER PT J AU Kelly, K Kittelson, J Franklin, WA Kennedy, TC Klein, CE Keith, RL Dempsey, EC Lewis, M Jackson, MK Hirsch, FR Bunn, PA Miller, YE AF Kelly, Karen Kittelson, John Franklin, Wilbur A. Kennedy, Timothy C. Klein, Catherine E. Keith, Robert L. Dempsey, Edward C. Lewis, Marina Jackson, Mary K. Hirsch, Fred R. Bunn, Paul A. Miller, York E. TI A Randomized Phase II Chemoprevention Trial of 13-CIS Retinoic Acid with Or without alpha Tocopherol or Observation in Subjects at High Risk for Lung Cancer SO CANCER PREVENTION RESEARCH LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; BRONCHIAL EPITHELIUM; FORMER SMOKERS; BETA-CAROTENE; VITAMIN-A; INTRAEPITHELIAL NEOPLASIA; 13-CIS-RETINOIC ACID; BREAST-CANCER; RECEPTOR-BETA; END-POINT AB No chemoprevention strategies have been proven effective for lung cancer. We evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without a tocopherol, as a lung cancer chemoprevention agent in a phase II randomized controlled clinical trial of adult subjects at high risk for lung cancer as defined by the presence of sputum atypia, history of smoking, and airflow obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free, >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA plus a tocopherol (13-cis RA/alpha toco) or observation for 12 months. Outcome measures are derived from histologic evaluation of bronchial biopsy specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome measure is treatment "failure" defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy. Seventy-five subjects were randomized (27/22/26 to obervations/13-cis RA/13-cis RA/alpha toco); 59 completed the trial; 55 had both baseline and follow-up bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of 48) in the observation and combined (13 cis RA plus 13 cis RA/alpha toco) treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97; 95% confidence interval, 0.36-2.66; P = 0.95). Among subjects with complete histology data, maximum histology score in the observation arm increased by 0.37 units and by 0.03 units in the treated arms (difference adjusted for baseline, -0.18; 95% confidence interval, -1.16 to 0.81; P = 0.72). Similar (nonsignificant) results were observed for treatment effects on endobronchial proliferation as assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced nonsignificant changes in bronchial histology, consistent with results in other trials. Agents advancing to phase III randomized trials should produce greater histologic changes. The addition of a tocopherol did not affect toxicity. C1 [Kelly, Karen; Klein, Catherine E.; Lewis, Marina; Jackson, Mary K.; Hirsch, Fred R.; Bunn, Paul A.] Univ Colorado, Div Med Oncol, Denver, CO 80202 USA. [Kittelson, John] Univ Colorado, Dept Biostat, Denver, CO 80202 USA. [Franklin, Wilbur A.; Lewis, Marina; Hirsch, Fred R.] Univ Colorado, Dept Pathol, Denver, CO 80202 USA. [Keith, Robert L.; Dempsey, Edward C.; Miller, York E.] Univ Colorado, Div Pulm Sci & Crit Care Med, Denver, CO 80202 USA. [Klein, Catherine E.; Keith, Robert L.; Dempsey, Edward C.; Miller, York E.] Denver VAMC, Denver, CO 80220 USA. [Kennedy, Timothy C.] Univ Colorado, Ctr Canc, HealthOne, Denver, CO 80262 USA. RP Miller, YE (reprint author), Denver VAMC, Pulm 111A,1055 Clermont St, Denver, CO 80220 USA. EM york.miller@uchsc.edu FU NIH/National Cancer Institute [P50 CA058187]; Lung Cancer NIH/National Cancer Institute [P30 CA46934] FX NIH/National Cancer Institute P50 CA058187 Specialized Programs of Research Excellence in Lung Cancer NIH/National Cancer Institute P30 CA46934 Cancer Center Core Grant. NR 40 TC 11 Z9 11 U1 0 U2 1 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 MAY PY 2009 VL 2 IS 5 BP 440 EP 449 DI 10.1158/1940-6207.CAPR-08-0136 PG 10 WC Oncology SC Oncology GA 441IU UT WOS:000265763300007 PM 19401528 ER PT J AU McDermott, U Ames, RY Iafrate, AJ Maheswaran, S Stubbs, H Greninger, P McCutcheon, K Milano, R Tam, A Lee, DY Lucien, L Brannigan, BW Ulkus, LE Ma, XJ Erlander, MG Haber, DA Sharma, SV Settleman, J AF McDermott, Ultan Ames, Rachel Y. Iafrate, A. John Maheswaran, Shyamala Stubbs, Hannah Greninger, Patricia McCutcheon, Kaitlin Milano, Randy Tam, Angela Lee, Diana Y. Lucien, Laury Brannigan, Brian W. Ulkus, Lindsey E. Ma, Xiao-Jun Erlander, Mark G. Haber, Daniel A. Sharma, Sreenath V. Settleman, Jeffrey TI Ligand-Dependent Platelet-Derived Growth Factor Receptor (PDGFR)-alpha Activation Sensitizes Rare Lung Cancer and Sarcoma Cells to PDGFR Kinase Inhibitors SO CANCER RESEARCH LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; THERAPEUTIC TARGET; IMATINIB MESYLATE; PHASE-II; EXPRESSION; MUTATIONS; FUSION; ALPHA; IDENTIFICATION; OSTEOSARCOMA AB Platelet-derived growth factor (PDGF) receptors (PDGFR) and their ligands play critical roles in several human malignancies. Sunitinib is a clinically approved multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor, c-KIT, and PDGFR, and has shown clinical activity in various solid tumors. Activation of PDGFR signaling has been described in gastrointestinal stromal tumors (PDGFRA mutations) as well as in chronic myeloid leukemia (BCR-PDGFRA translocation), and sunitinib can yield clinical benefit in both settings. However, the discovery of PDGFR activating mutations or gene rearrangements in other tumor types could reveal additional patient populations who might benefit from treatment with anti-PDGFR therapies, such as sunitinib. Using a high-throughput cancer cell line screening platform, we found that only 2 of 637 tested human tumor-derived cell lines show significant sensitivity to single-agent sunitinib exposure. These two cell lines [a non-small-cell lung cancer (NSCLC) and a rhabdomyosarcoma] showed expression of highly phosphorylated PDGFRA. In the sunitinib-sensitive adenosquamous NSCLC cell line, PDGFRA expression was associated with focal PFGRA gene amplification, which was similarly detected in a small fraction of squamous cell NSCLC primary tumor specimens. Moreover, in this NSCLC cell line, focal amplification of the gene encoding the PDGFR ligand PDGFC was also detected, and silencing PDGFRA or PDGFC expression by RNA interference inhibited proliferation. A similar codependency on PDGFRA and PDGFC was observed in the sunitinib-sensitive rhabdomyosarcoma cell line. These findings suggest that, in addition to gastrointestinal stromal tumors, rare tumors that show PDGFC-mediated PDGFRA activation may also be clinically responsive to pharmacologic PDGFRA or PDGFC inhibition. [Cancer Res 2009;69(9):3937-46] C1 [McDermott, Ultan; Ames, Rachel Y.; Maheswaran, Shyamala; Greninger, Patricia; McCutcheon, Kaitlin; Milano, Randy; Tam, Angela; Lee, Diana Y.; Lucien, Laury; Brannigan, Brian W.; Ulkus, Lindsey E.; Haber, Daniel A.; Sharma, Sreenath V.; Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA. [McDermott, Ultan; Ames, Rachel Y.; Maheswaran, Shyamala; Greninger, Patricia; McCutcheon, Kaitlin; Milano, Randy; Tam, Angela; Lee, Diana Y.; Lucien, Laury; Brannigan, Brian W.; Ulkus, Lindsey E.; Haber, Daniel A.; Sharma, Sreenath V.; Settleman, Jeffrey] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Iafrate, A. John; Stubbs, Hannah] Massachusetts Gen Hosp, Dept Pathol, Mol Diagnost Lab, Boston, MA 02114 USA. [Iafrate, A. John; Stubbs, Hannah] Harvard Univ, Sch Med, Boston, MA USA. [Ma, Xiao-Jun; Erlander, Mark G.] AviaraDx Inc, Carlsbad, CA USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, 149 13th St, Charlestown, MA 02129 USA. EM Settleman@helix.mgh.harvard.edu OI Ames, Rachel/0000-0002-1550-2148; McDermott, Ultan/0000-0001-9032-4700 FU National Cancer Institute Specialized Program of Research Excellence in Lung Cancer [P20 CA090578-06] FX National Cancer Institute Specialized Program of Research Excellence in Lung Cancer award P20 CA090578-06. NR 31 TC 54 Z9 56 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 IS 9 BP 3937 EP 3946 DI 10.1158/0008-5472.CAN-08-4327 PG 10 WC Oncology SC Oncology GA 441IG UT WOS:000265761900028 PM 19366796 ER PT J AU Abangan, R Williams, C LaRue, A AF Abangan, Romeo Williams, Christopher LaRue, Amanda TI Regulation of hematopoietic stem cell-derived circulating fibroblast precursors in solid tumor formation SO CANCER RESEARCH LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3172 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803464 ER PT J AU Abu-Yousif, A Zheng, X Moore, A Hasan, T AF Abu-Yousif, Adnan Zheng, Xiang Moore, Anne Hasan, Tayyaba TI Photoimmunotherapy (PIT) for the selective destruction of ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Abu-Yousif, Adnan; Zheng, Xiang; Moore, Anne; Hasan, Tayyaba] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3254 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702605414 ER PT J AU Ahmad, R Raina, D Joshi, MD Kharbanda, S Kawano, T Kufe, D AF Ahmad, Rehan Raina, Deepak Joshi, Maya Datt Kharbanda, Surender Kawano, Takeshi Kufe, Donald TI MUC1-C oncoprotein function as a direct activator of the NF-kB p65 transcription factor SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Genus Oncol Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4251 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802220 ER PT J AU Alt, F Wang, J Gostissa, M Boboila, C Yan, C AF Alt, Frederick Wang, Jing Gostissa, Monica Boboila, Cristian Yan, Catherine TI Invited Speaker SO CANCER RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA ME40-1 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804177 ER PT J AU Asomaning, K Zhai, RH Heist, R Liu, G Wain, J Lynch, T Su, L Lin, XH Christiani, D AF Asomaning, Kofi Zhai, Rihong Heist, Rebecca Liu, Geoffrey Wain, John Lynch, Thomas Su, Li Lin, Xihong Christiani, David TI Nicotinic acetylcholine receptor polymorphisms, smoking and lung cancer risk SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 105 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704055 ER PT J AU Baba, Y Nosho, K Shima, K Irahara, N Kure, S Toyoda, S Kirkner, G Goel, A Fuchs, C Ogino, S AF Baba, Yoshifumi Nosho, Katsuhiko Shima, Kaori Irahara, Natsumi Kure, Shoko Toyoda, Saori Kirkner, Gregory Goel, Ajay Fuchs, Charles Ogino, Shuji TI AURKA (Aurora-A) expression is independently associated with chromosomal instability in colorectal cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Baylor Univ, Med Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1305 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801386 ER PT J AU Bailey, S Brown, M AF Bailey, Shannon Brown, Myles TI Elucidating the mechanism of ER-p53 cross-talk in breast cancer cells. SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Bailey, Shannon; Brown, Myles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1491 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804292 ER PT J AU Benedettini, E Vena, N Bailey, D Fiorentino, M Fornari, A Bosari, S Chirieac, L Lutterbach, B Loda, M AF Benedettini, Elisa Vena, Natalie Bailey, Dyane Fiorentino, Michelangelo Fornari, Alessandro Bosari, Silvano Chirieac, Lucian Lutterbach, Bart Loda, Massimo TI Met activation sustains a metastatic phenotype in non-small cell lung cancer patients and is associated with KRAS mutation SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Turin, Turin, Italy. Univ Milan, Milan, Italy. Brigham & Womens Hosp, Boston, MA 02115 USA. Merck Res Labs, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4808 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803233 ER PT J AU Berger, M Levin, J Sougnez, C Cibulskis, K Getz, G Sivachenko, A Maguire, J Barretina, J Stransky, N Fennell, T Vijayendran, K Adiconis, X Laine, E Lawrence, M Gnirke, A Dummer, R Meyerson, M Nusbaum, C Lander, E Jaffe, D Gabriel, S Garraway, L AF Berger, Michael Levin, Joshua Sougnez, Carrie Cibulskis, Kristian Getz, Gad Sivachenko, Andrey Maguire, Jared Barretina, Jordi Stransky, Nicolas Fennell, Timothy Vijayendran, Krishna Adiconis, Xian Laine, Elisabeth Lawrence, Michael Gnirke, Andreas Dummer, Reinhard Meyerson, Matthew Nusbaum, Chad Lander, Eric Jaffe, David Gabriel, Stacey Garraway, Levi TI Next-generation sequencing for large-scale cancer gene mutation profiling SO CANCER RESEARCH LA English DT Meeting Abstract C1 Broad Inst MIT & Harvard, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Zurich Hosp, CH-8091 Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5201 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802256 ER PT J AU Bhatt, R Wang, XE Zhang, L Bullock, A Bhasin, M Libermann, T Signoretti, S O'Neill, A Atkins, M Mier, J Goldberg, S AF Bhatt, Rupal Wang, Xiaoen Zhang, Liang Bullock, Andrea Bhasin, Manoj Libermann, Towia Signoretti, Sabina O'Neill, Anne Atkins, Michael Mier, James Goldberg, S. TI Cox-2 inhibition delays resistance to sunitinib in RCC xenograft models SO CANCER RESEARCH LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 153 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603009 ER PT J AU Bonneau, M Cleverly, K Birrer, M Wu, T Farley, J AF Bonneau, Michelle Cleverly, Kirsty Birrer, Michael Wu, T. Farley, John TI The role of the estrogen receptor on cervical cancer proliferation SO CANCER RESEARCH LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2381 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703008 ER PT J AU Bornhauser, B Bonapace, L Schmitz, M Stanulla, M Schrappe, M Walensky, L Bourquin, JP AF Bornhauser, Beat Bonapace, Laura Schmitz, Maike Stanulla, Martin Schrappe, Martin Walensky, Loren Bourquin, Jean-Pierre TI Induction of autophagy-dependent cell death is required to restore steroid sensitivity in steroid-resistant ALL SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Childrens Hosp, Zurich, Switzerland. Univ Hosp, Kiel, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5644 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802142 ER PT J AU Broome, AM Bhavsar, N Glazer, D Ramamurthy, G Newton, G Basilion, J AF Broome, Ann-Marie Bhavsar, Nihir Glazer, Daniel Ramamurthy, Gopal Newton, Gail Basilion, James TI Imaging complex molecular signatures in cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4317 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802389 ER PT J AU Castaigne, JP Mikkelsen, T Schiff, D Wen, P Rosenfeld, S Groves, M Wong, E Elian, K Neale, A Lawrence, B Drappatz, J AF Castaigne, Jean-Paul Mikkelsen, Tom Schiff, David Wen, Patrick Rosenfeld, Steven Groves, Morris Wong, Eric Elian, Kelly Neale, Ann Lawrence, Betty Drappatz, Jan TI ANG1005 (Angiopep-2/paclitaxel conjugate) as a promising new drug therapy for patients with malignant glioma SO CANCER RESEARCH LA English DT Meeting Abstract C1 Angiochem Inc, Montreal, PQ, Canada. Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 USA. Univ Virginia Hlth Syst, Charlottesville, VA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Columbia Univ, Med Ctr, New York, NY USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. WinPharm Associates LLC, Danville, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3781 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802326 ER PT J AU Chakrabarty, A Rexer, B Engelman, J Arteaga, C AF Chakrabarty, Anindita Rexer, Brent Engelman, Jeffrey Arteaga, Carlos TI H1047R PIK3CA mutant enhances HER2-mediated transformation via heregulin production and activation of HER3 in human mammary epithelial cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 440 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703340 ER PT J AU Chavarro, J Stampfer, M Loda, M Campos, H Sesso, H Ma, J AF Chavarro, Jorge Stampfer, Meir Loda, Massimo Campos, Hannia Sesso, Howard Ma, Jing TI Blood levels of saturated and mono-unsaturated fatty acids and risk of prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 72 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702705005 ER PT J AU Chin, YMR Toker, A AF Chin, Yuet Ming Rebecca Toker, Alex TI Differential regulation of breast cancer cell invasive migration by Akt isoforms SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Chin, Yuet Ming Rebecca; Toker, Alex] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3819 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801247 ER PT J AU Cho, D Cohen, M Panka, D Bhatt, R Signoretti, S Atkins, M Mier, J AF Cho, Daniel Cohen, Matthew Panka, David Bhatt, Rupal Signoretti, Sabina Atkins, Michael Mier, James TI In vitro and in vivo efficacy of the dual PI3-kinase/mTOR inhibitor NVP-BEZ235 in renal cell carcinoma (RCC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2749 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804121 ER PT J AU Cho, E Hankinson, S Curhan, G Atkins, M Stampfer, M Choueiri, T AF Cho, Eunyoung Hankinson, Susan Curhan, Gary Atkins, Michael Stampfer, Meir Choueiri, Toni CA Ogram Dana-Farber Harvard Canc Ctr TI Prospective study of use of analgesics in relation to the risk of renal cell cancer: The Nurses' Health Study and Health Professionals Follow-up Study SO CANCER RESEARCH LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4864 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704367 ER PT J AU Chung, R AF Chung, Raymond TI Viral hepatocarcinogenesis: Two routes to a common destination SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Chung, Raymond] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA SY39-3 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701800054 ER PT J AU Cirstea, D Hideshima, T Santo, L Vallet, S Pozzi, S Vaghela, N Ikeda, H Patel, K Loferer, H Gorgun, G Perrone, G Calabrese, E Munshi, N Anderson, K Raje, N AF Cirstea, Diana Hideshima, Teru Santo, Loredana Vallet, Sonia Pozzi, Samantha Vaghela, Nileshwari Ikeda, Hiroshi Patel, Kishan Loferer, Hannes Gorgun, Gullu Perrone, Giulia Calabrese, Elisabetta Munshi, Nikhil Anderson, Kenneth Raje, Noopur TI A novel multi-targeted small molecule inhibitor RGB 286638 triggers apoptosis and necrosis in multiple myeloma via dual cell death pathways SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. GPC Biotech AG, Munich, Germany. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1994 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604382 ER PT J AU Cramer, D Bast, R Clarke, C Coombes, K Diamandis, E Fung, E Godwin, A Lockshin, A Lu, KR McIntosh, M Mor, G Skates, S Sluss, P Thornquist, M Zhang, Z Urban, N AF Cramer, Daniel Bast, Robert Clarke, Charlotte Coombes, Kevin Diamandis, Eleftherios Fung, Eric Godwin, Andrew Lockshin, Anna Lu, Karen McIntosh, Martin Mor, Gil Skates, Steve Sluss, Patrick Thornquist, Mark Zhang, Zhen Urban, Nicole TI Phase III validation of ovarian cancer biomarkers in pre-diagnostic specimens from the PLCO screening trial SO CANCER RESEARCH LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Vermillion Inc, Fremont, CA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Pittsburgh, Inst Canc, Philadelphia, PA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Yale Reprod Endocrinol & Infertil, New Haven, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-96 PG 2 WC Oncology SC Oncology GA V43TD UT WOS:000209702801248 ER PT J AU Davis, J Jiang, C Growdon, W Remmenga, S Rueda, B AF Davis, John Jiang, Chao Growdon, Whitfield Remmenga, Steve Rueda, Bo TI Rac1b expression is an indicator of poor survival in patients with serous ovarian cancer: functional contributions to the aggressive nature of the disease SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Nebraska Med Ctr, Omaha, NE USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2495 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802487 ER PT J AU Di Tomaso, E London, N Fuja, D Logie, J Munn, L Jain, R AF Di Tomaso, Emmanuelle London, Nyall Fuja, Daniel Logie, James Munn, Lance Jain, Rakesh TI PDGF-CC normalizes vessels in glioblastoma xenorafts SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Utah, Salt Lake City, UT USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Edinburgh, Edinburgh, Midlothian, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2005 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803085 ER PT J AU Duan, ZF Choy, E Yang, C Schwab, J Mankin, H Hornicek, F AF Duan, Zhenfeng Choy, Edwin Yang, Cao Schwab, Joseph Mankin, Henry Hornicek, Francis TI The small molecule Tetradrine (NSC77037), identified in a high-throughput cell-based screen, reverses multidrug resistance in cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Duan, Zhenfeng; Choy, Edwin; Yang, Cao; Schwab, Joseph; Mankin, Henry; Hornicek, Francis] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 905 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802014 ER PT J AU Duan, ZF Choy, E Yang, C Schwab, J Del Maria, C Mankin, H Hornicek, F AF Duan, Zhenfeng Choy, Edwin Yang, Cao Schwab, Joseph Del Maria, Carmen Mankin, Henry Hornicek, Francis TI ZNF93 overexpression is associated with ET-743 (Trabectedin; Yondelis) and PM00104 (Zalypsis) resistance in human cancer cell lines SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. PharmaMar USA, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5533 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803232 ER PT J AU Dutt, A Salvesan, H Chen, T Greulich, H Meyerson, M AF Dutt, Amit Salvesan, Helga Chen, Tzu Greulich, Heidi Meyerson, Matthew TI Discovery of EGFR and FGFR2 as therapeutic targets in endometrial cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Haukeland Hosp, N-5021 Bergen, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2590 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804060 ER PT J AU El-Jawahri, A Lautenschlaeger, T Patel, D Chakravarti, A AF El-Jawahri, Areej Lautenschlaeger, Tim Patel, Disha Chakravarti, Arnab TI Galectin-3 mediates resistance to radiotherapy through the activation of p-ERK independent of Ras activation SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3961 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804023 ER PT J AU Ercan, D Zejnullahu, K Xiao, Y Capelletti, M Rogers, A Lee, C Christensen, J Janne, P AF Ercan, Dalia Zejnullahu, Kreshnik Xiao, Yun Capelletti, Marzia Rogers, Andrew Lee, Charles Christensen, James Janne, Pasi TI Amplification of EGFR T790M causes resistance to the irreversible EGFR inhibitor PF00299804 SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Pfizer, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4711 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802211 ER PT J AU Ferrandiz, N Martin-Perez, J Blanco, R Donertas, D Weber, A Paolo, D Eilers, M Delgado, MD Leon, J AF Ferrandiz, Nuria Martin-Perez, Jorge Blanco, Rosa Donertas, Derya Weber, Axel Paolo, Dotto Eilers, Martin Delgado, M. Dolores Leon, Javier TI Colon cancer HCT116 cells deficient in p21/Cip1 are hypersensitive to tyrosine kinase inhibitors imatinib and gefitinib through a mechanism unrelated to p21 and dependent on p53 hyperactivity SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Cantabria CSIC, IBBTEC, Santander, Spain. CSIC, Inst Invest Biomed, Madrid, Spain. Univ Marburg, Inst Tumor Biol, Marburg, Germany. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 609 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804407 ER PT J AU Fuchs, B Fujii, T McGinn, C Kuroda, T Lanuti, M Tanabe, K AF Fuchs, Bryan Fujii, Tsutomu McGinn, Christopher Kuroda, Toshihiko Lanuti, Michael Tanabe, Kenneth TI Erlotinib chemoprevention of hepatocellular carcinoma in a rat model of cirrhosis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Fuchs, Bryan; Fujii, Tsutomu; McGinn, Christopher; Kuroda, Toshihiko; Lanuti, Michael; Tanabe, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 939 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702801270 ER PT J AU Ge, RB Wang, ZW Olumi, A AF Ge, Rongbin Wang, Zongwei Olumi, Aria TI F-box protein 10: a novel anti-apoptotic protein regulates TRAIL-induced apoptosis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Ge, Rongbin; Wang, Zongwei; Olumi, Aria] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2038 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802092 ER PT J AU Gokhale, A Epperly, M Glowacki, J Wang, H Smith, T Patrene, K Roodman, G Greenberger, J AF Gokhale, Abhay Epperly, Michael Glowacki, Julie Wang, Hong Smith, Tracy Patrene, Kenneth Roodman, G. Greenberger, Joel TI Antioxidant therapy ameliorates ionizing irradiation-induced delay in bone wound healing SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Pittsburgh, Dept Radiat Oncol, Inst Canc, Pittsburgh, PA USA. Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Div Hematol Oncol, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3966 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804028 ER PT J AU Gonzalez-Perez, R Watters, A Xu, YB Singh, U Mann, D Rueda, B Penichet, M AF Gonzalez-Perez, Ruben Watters, Amber Xu, Yanbo Singh, Udai Mann, David Rueda, Bo Penichet, Manuel TI Differential effects of leptin-peptide receptor antagonist (LPrA) on breast cancer estrogen receptor positive and negative SO CANCER RESEARCH LA English DT Meeting Abstract C1 Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA. Morehouse Sch Med, Cooperat Reprod Sci Res Ctr, Atlanta, GA 30310 USA. Morehouse Sch Med, Dept Physiol, Atlanta, GA 30310 USA. Univ S Carolina, Dept Pathol Microbiol & Immunol, Sch Med Columbia, Columbia, SC 29208 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Vincent Ctr Reprod Biol,Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Surg, Dept Microbiol Immunol & Mol Genet, Div Surg Oncol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4704 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604314 ER PT J AU Hardcastle, J Kurozumi, K Sayers, M Dmitrieva, N Ahmad, S Waterman, P Chiocca, E Weissleder, R Kaur, B AF Hardcastle, Jayson Kurozumi, Kazuhiko Sayers, Martin Dmitrieva, Nina Ahmad, Sarwat Waterman, Peter Chiocca, E. Weissleder, Ralph Kaur, Balveen TI Antitumor efficacy of Vasculostatin (Vstat120) gene delivery with a tumor-specific replication competent oncolytic virus SO CANCER RESEARCH LA English DT Meeting Abstract C1 Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 130 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702602477 ER PT J AU Heist, R Zhai, RH Asomaning, K Wang, ZX Liu, G Su, L Neuberg, D Lynch, T Wain, J Christiani, D AF Heist, Rebecca Zhai, Rihong Asomaning, Kofi Wang, Zhaoxi Liu, Geoffrey Su, Li Neuberg, Donna Lynch, Thomas Wain, John Christiani, David TI Nicotinic acetylcholine receptor polymorphisms and survival in early stage non-small cell lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4841 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703464 ER PT J AU Hettmer, S Jurga, S Bronson, R Mao, JH Wagers, A AF Hettmer, Simone Jurga, Sara Bronson, Roderick Mao, Junhao Wagers, Amy TI Cellular composition of mouse embryonal rhabdomyosarcoma tumors compared to normal skeletal muscle. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Stem Cell Inst, Boston, MA USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. Univ Massachusetts, Sch Med, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2443 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801039 ER PT J AU Hirata, H Hinoda, Y Kikuno, N Kawakami, K Suehiro, Y Yamamura, S Dahiya, R AF Hirata, Hiroshi Hinoda, Yuji Kikuno, Nobuyuki Kawakami, Kazumori Suehiro, Yutaka Yamamura, Soichiro Dahiya, Rajvir TI BCL2-938C/A polymorphism has increased risk of biochemical recurrence after radical prostatectomy in sporadic prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Yamaguchi Univ, Grad Sch Med, Ube, Yamaguchi 755, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1665 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702025 ER PT J AU Hofer, M Bauer, D Sallan, S Schwartz, B Cameron, M West, N Agoston, E Ince, T Janeway, K Aster, J Bradner, J French, C AF Hofer, Matthias Bauer, Daniel Sallan, Stephen Schwartz, Brian Cameron, Michael West, Nathan Agoston, Elin Ince, Tan Janeway, Katherine Aster, Jon Bradner, James French, Christopher TI Rationale and use of single-agent histone deacetylase inhibitor therapy in poorly differentiated midline carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Broad Inst Harvard & MIT, Cambridge, MA USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1901 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703001 ER PT J AU Houvras, Y Ceol, C Lin, W Jane-Valbuena, J Ferre, F Burke, C Bourque, C Turner, L Uong, A Garraway, L Zon, L AF Houvras, Yariv Ceol, Craig Lin, William Jane-Valbuena, Judit Ferre, Fabrizio Burke, Christopher Bourque, Caitlin Turner, Laura Uong, Audrey Garraway, Levi Zon, Leonard TI A novel screening approach in zebrafish identifies SETDB1, a histone methyltransferase, as an oncogene in human melanoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp Boston, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard, Boston, MA USA. Broad Inst MIT & Harvard, Boston, MA USA. Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2078 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804378 ER PT J AU Huang, YT Chirieac, L Lin, XH Wain, J Heist, R Skaug, V Zienolddiny, S Haugen, A Su, L Christiani, D AF Huang, Yen-Tsung Chirieac, Lucian Lin, Xihong Wain, John Heist, Rebecca Skaug, Vidar Zienolddiny, Shanbeh Haugen, Aage Su, Li Christiani, David TI Characterizing genome-wide copy number profiles in non-small cell lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Inst Occupat Hlth, Oslo, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1405 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803472 ER PT J AU Idbaih, A Inda, MD Ligon, A Chin, L Cavenee, W Furnari, F Kho, A Delattre, JY Kung, A Rowitch, D Ligon, K AF Idbaih, Ahmed Inda, Maria-del-Mar Ligon, Azra Chin, Lynda Cavenee, Webster Furnari, Franck Kho, Alvin Delattre, Jean-Yves Kung, Andrew Rowitch, David Ligon, Keith TI Transcription factor screening identifies SOX2 as a critical gene in glioblastoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Childrens Hosp Boston, Boston, MA USA. Grp Hosp Pitie Salpetriere, F-75634 Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1943 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803398 ER PT J AU Ide, T Brown, L Ongusaha, P Raj, L Kim, HG Lee, S AF Ide, Takao Brown, Lauren Ongusaha, Pat Raj, Lakshmi Kim, Hyung Gu Lee, Sam TI GAMT, a p53-inducible modulator of apoptosis and autophagy, is critical for adaptive response to metabolic stress SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Ide, Takao; Brown, Lauren; Ongusaha, Pat; Raj, Lakshmi; Kim, Hyung Gu; Lee, Sam] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1873 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800421 ER PT J AU Ioffe, Y Xu, X Xing, DY Oliva, E Karlan, B Orsulic, S AF Ioffe, Yevgeniya Xu, Xuan Xing, Deyin Oliva, Esther Karlan, Beth Orsulic, Sandra TI BRCA1 expression is downregulated in uterine Ieiomyosarcomas SO CANCER RESEARCH LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Med, Boston, MA USA. Cedars Sinai Med Ctr, Womens Canc Res Inst, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4437 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804440 ER PT J AU Jeyaretna, D Wakimoto, H Kesari, S Rabkin, S Martuza, R AF Jeyaretna, Deva Wakimoto, Hiroaki Kesari, Santosh Rabkin, Samuel Martuza, Robert TI Attacking the glioblastoma stem cell fraction using an oncolytic herpes simplex virus and bevacizumab SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3783 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802328 ER PT J AU Jiang, JR Zhang, Y Askenazi, M Marto, JA Griffin, JD AF Jiang, Jingrui Zhang, Yi Askenazi, Manor Marto, Jarrod A. Griffin, James D. TI Phosphoproteomics analysis reveals distinct tyrosine phosphorylation patterns between the ITD and D835Y mutant FLT3 tyrosine kinase receptors SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Jiang, Jingrui; Zhang, Yi; Askenazi, Manor; Marto, Jarrod A.; Griffin, James D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3395 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802467 ER PT J AU Jin, BF Shen, HX Li, JL Griffin, J Wu, LZ AF Jin, Baofeng Shen, Huangxuan Li, Jian-Liang Griffin, James Wu, Lizi TI Identification of the MAML1 co-activator as a novel modulator for NF-\#954;B signaling SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL USA. Univ Florida, Interdisciplinary Ctr Biotechnol Res, Gainesville, FL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Florida, Shands Canc Ctr, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5277 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803406 ER PT J AU Jinushi, M Sato, M Kanamoto, A Itoh, A Mihm, M Dranoff, G Tahara, H AF Jinushi, Masahisa Sato, Marimo Kanamoto, Akira Itoh, Akihiko Mihm, Martin Dranoff, Glenn Tahara, Hideaki TI The role of tumor-derived MFG-E8 in triggering chemoresistance and immune suppression in patients with various solid tumors SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Tokyo, Tokyo, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2865 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802265 ER PT J AU Johnson, N Cai, DP Kennedy, R Pathania, S Parvin, J D'Andrea, A Shapiro, G AF Johnson, Neil Cai, Dongpo Kennedy, Richard Pathania, Shailja Parvin, Jeffrey D'Andrea, Alan Shapiro, Geoffrey TI Cdk1 depletion disrupts BRCA1 function and selectively sensitizes cancer cells to DNA damaging agents SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber, Boston, MA USA. Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3316 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801177 ER PT J AU Kamoun, W DanLey, C Farrar, C Duyverman, A Landenranta, J Lacorre, D Batchelor, T diTomaso, E Duda, D Munn, L Fukumura, D Sorensen, G Jain, R AF Kamoun, Walid DanLey, Carsten Farrar, Christian Duyverman, Annique Landenranta, Johanna Lacorre, Delphine Batchelor, Tracy diTomaso, Emmanuelle Duda, Dan Munn, Lance Fukumura, Dai Sorensen, Gregory Jain, Rakesh TI Edema control by cediranib, a VEGF targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kamoun, Walid; DanLey, Carsten; Farrar, Christian; Duyverman, Annique; Landenranta, Johanna; Lacorre, Delphine; Batchelor, Tracy; diTomaso, Emmanuelle; Duda, Dan; Munn, Lance; Fukumura, Dai; Sorensen, Gregory; Jain, Rakesh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4087 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804230 ER PT J AU Karl, D Lee, YJ Maduekwe, U Rothrock, C Yoon, S AF Karl, Daniel Lee, Yoon-Jin Maduekwe, Ugwuji Rothrock, Courtney Yoon, Sam TI Differential effects of VEGFR-2 inhibition in the liver and lung SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Karl, Daniel; Lee, Yoon-Jin; Maduekwe, Ugwuji; Rothrock, Courtney; Yoon, Sam] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1110 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603345 ER PT J AU Kim, JB Urban, K Barton, E Kung, AL Lassota, P AF Kim, Jae-Beom Urban, Konnie Barton, Eva Kung, Andrew L. Lassota, Peter TI Direct comparison of in vivo fluorescence and bioluminescence of dually labeled cancer cells. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Caliper Life Sci, Alameda, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3999 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803209 ER PT J AU Koleva, R Ficarro, S Askenazi, M Parikh, J Li, SJ Luckey, C Marto, J AF Koleva, Rositsa Ficarro, Scott Askenazi, Manor Parikh, Jignesh Li, Shaojuan Luckey, Chance Marto, Jarrod TI Dynamic remodeling of CEBP\#945; complexes in myeloid differentiation and Leukemogenesis SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. BWH, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1511 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804310 ER PT J AU Lang, J Xing, DY Orsulic, S AF Lang, Jennifer Xing, Deyin Orsulic, Sandra TI Global analysis of differentially expressed genes in BRCA1-deficient murine ovarian cancer cell lines SO CANCER RESEARCH LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 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 AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1443 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803286 ER PT J AU Lanning, R Vakoc, B Padera, T Tyrrell, J Bartlett, L Stylianopoulos, T Munn, L Tearney, G Fukumura, D Jain, R Bouma, B AF Lanning, Ryan Vakoc, Benjamin Padera, Timothy Tyrrell, James Bartlett, Lisa Stylianopoulos, Triantafyllos Munn, Lance Tearney, Guillermo Fukumura, Dai Jain, Rakesh Bouma, Brett TI In vivo dissection of tumor vascular networks, lymphatics, tissue viability and microenvironment using three-dimensional optical frequency domain imaging SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Lanning, Ryan; Vakoc, Benjamin; Padera, Timothy; Tyrrell, James; Bartlett, Lisa; Stylianopoulos, Triantafyllos; Munn, Lance; Tearney, Guillermo; Fukumura, Dai; Jain, Rakesh; Bouma, Brett] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4310 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802382 ER PT J AU Lautenschlaeger, T Patel, D EI-Jawahri, A Palanichamy, K Chakrvarti, A AF Lautenschlaeger, Tim Patel, Disha EI-Jawahri, Areej Palanichamy, Kamalakannan Chakrvarti, Arnab TI Galectin-1 mediates resistance to radiotherapy through control of PI3 Kinase activity SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Lautenschlaeger, Tim; Patel, Disha; EI-Jawahri, Areej; Palanichamy, Kamalakannan; Chakrvarti, Arnab] Mass Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3960 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804021 ER PT J AU Lee, JE Willett, W Fuchs, C Ma, J Smith-Warner, S Wu, K Giovannucci, E AF Lee, Jung Eun Willett, Walter Fuchs, Charles Ma, Jing Smith-Warner, Stephanie Wu, Kana Giovannucci, Edward TI Folate intake and the risk of colorectal cancer and adenoma in two large prospective studies: modification by time SO CANCER RESEARCH LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1979 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703106 ER PT J AU Letai, A AF Letai, Anthony TI Targeting BCL-2 family control of apoptosis in cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Letai, Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA SY34-1 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800039 ER PT J AU Li, J Wang, LL Janne, PA Makrigiorgos, GM AF Li, Jin Wang, Lilin Janne, Pasi A. Makrigiorgos, G. Mike TI Cold-pcr increases mutation detection selectivity of taqman-based real-time pcr SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Li, Jin; Wang, Lilin; Janne, Pasi A.; Makrigiorgos, G. Mike] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 749 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702087 ER PT J AU Lim, K Shin, ES Song, KS Kim, YJ Kim, JS Park, HD Yang, HR Kang, JX Park, JI Kweon, GR Yoon, WH Hwang, BD AF Lim, Kyu Shin, Eul-Soon Song, Kyoung-Sub Kim, Young-Jo Kim, Jong-Seok Park, Hae-Duck Yang, Hae-Rim Kang, Jing X. Park, Jong-ii Kweon, Gi-Ryang Yoon, Wan-Hee Hwang, Byung-Doo TI Anti-cancer action of Omega-3 polyunsaturated fatty acids in colon cancer: In vitro and Fat1 transgenic mice model SO CANCER RESEARCH LA English DT Meeting Abstract C1 Chungnam Natl Univ, Daejeon, South Korea. Dr Parks Breast Clin, Daejeon, South Korea. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3751 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604160 ER PT J AU Lim, K Yun, EJ Song, KS Park, HD Kim, JS Shin, ES Han, C Wu, T Kang, JX Park, JI Kweon, GR Yoon, WH Hwang, BD AF Lim, Kyu Yun, Eun-Jin Song, Kyoung-Sub Park, Hae-Duck Kim, Jong-Seok Shin, Eul-Soon Han, Chang Wu, Tong Kang, Jing X. Park, Jong-ii Kweon, Gi-Ryang Yoon, Wan-Hee Hwang, Byung-Doo TI Omega-3 polyunsaturated fatty acids suppress cell invasion, tumorigenicity, angiogenesis, and metastasis by inhibition of MMPs/VEGF through NF-kB and AP-1 signal in breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Chungnam Natl Univ, Daejeon, South Korea. Dr Parks Breast Clin, Daejeon, South Korea. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3749 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604158 ER PT J AU Lim, K Song, KS Kim, JS Yun, EJ Park, HD Shin, ES Han, C Wu, T Kang, JX Park, JI Kweon, GR Yoon, WH Hwang, BD AF Lim, Kyu Song, Kyoung-Sub Kim, Jong-Seok Yun, Eun-Jin Park, Hae-Duck Shin, Eul-Soon Han, Chang Wu, Tong Kang, Jing X. Park, Jong-Il Kweon, Gi-Ryang Yoon, Wan-Hee Hwang, Byung-Doo TI Anti-angiogenic effect of w3-polyunsaturated fatty acids is mediated through suppression of ELR plus CXC chemokines expression and VEGF signaling in pancreatic cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Chungnam Natl Univ, Daejeon, South Korea. Dr Parks Breast Clin, Daejeon, South Korea. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 131 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702602478 ER PT J AU LoRusso, P Demuth, T Heath, E Malburg, L Pilat, MJ Kesari, S Russak, J Knowles, J Beckman, R Fang, LY Stone, J Krop, I AF LoRusso, Patricia Demuth, Tim Heath, Elisabeth Malburg, Lisa Pilat, Mary Jo Kesari, Santosh Russak, Jason Knowles, James Beckman, Robert Fang, Lanyan Stone, Julie Krop, Ian TI Phase I study of the Gamma Secretase Inhibitor MK-0752 in patients with metastatic breast and other advanced solid tumors SO CANCER RESEARCH LA English DT Meeting Abstract C1 Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Merck Res Labs, N Wales, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3605 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805447 ER PT J AU MacConaill, L Campbell, C Kehoe, S Hatton, C Davis, M Niu, LL Yao, KL Hanna, M Berger, M Stransky, N Barretina, J Polyak, K Hahn, W Meyerson, M Garraway, L AF MacConaill, Laura Campbell, Catarina Kehoe, Sarah Hatton, Charlie Davis, Matt Niu, Lili Yao, Keluo Hanna, Megan Berger, Michael Stransky, Nicolas Barretina, Jordi Polyak, Kornelia Hahn, William Meyerson, Matthew Garraway, Levi TI The \#8220;OncoMap\#8221;: High-throughput profiling of critical genetic mutations in clinical tumor samples SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. Broad Inst Harvard & MIT, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1892 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702397 ER PT J AU Marshall, A Heist, R Asomaning, K Zhai, RH Wang, ZX Su, L Neuberg, D Lynch, T Wain, J Christiani, D AF Marshall, Ariela Heist, Rebecca Asomaning, Kofi Zhai, Rihong Wang, Zhaoxi Su, Li Neuberg, Donna Lynch, Thomas Wain, John Christiani, David TI TP53-binding protein 1 (TP53BP1) polymorphism is associated with survival in limited stage small cell lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4848 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703472 ER PT J AU McGinn, C Goodwin, J Fuchs, B Tanabe, K Lanuti, M AF McGinn, Christopher Goodwin, Jonathan Fuchs, Bryan Tanabe, Kenneth Lanuti, Michael TI Influence of solid tumor matrix on viral oncolysis: Analysis in a multicellular tumor spheroid model SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Diego, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1134 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802100 ER PT J AU Milbury, C Li, J Makrigiorgos, GM AF Milbury, Coren Li, Jin Makrigiorgos, G. Mike TI Combination of COLD-PCR and High-Resolution Melting provides a highly sensitive approach for efficient scanning and identification of low-level unknown cancer mutations SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Milbury, Coren; Li, Jin; Makrigiorgos, G. Mike] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4334 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803256 ER PT J AU Moellering, R Ramirez, R Verdine, G Bradner, J AF Moellering, Raymond Ramirez, Ricardo Verdine, Gregory Bradner, James TI Rational targeting of notch receptor trafficking SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5363 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701086 ER PT J AU Moellering, R Cornejo, M Davis, T Del Bianco, C Aster, J Blacklow, S Kung, A Gilliland, DG Verdine, G Bradner, J AF Moellering, Raymond Cornejo, Melanie Davis, Tina Del Bianco, Cristina Aster, Jon Blacklow, Stephen Kung, Andrew Gilliland, D. Gary Verdine, Gregory Bradner, James TI Targeted disruption of the Notch transcription factor complex in vitro and in vivo SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 841 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604394 ER PT J AU Mok, S Ghosh, S Kwong, J Welch, W Gershenson, D Birrer, M Wong, KK AF Mok, Samuel Ghosh, Sue Kwong, Joseph Welch, William Gershenson, David Birrer, Michael Wong, Kwong-Kwok TI Nuclear Elf-3 expression in high-grade serous ovarian cancer is associated with patient survival SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2715 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702115 ER PT J AU Nagrath, S Maheswaran, S Sequist, L Ulkus, L Brannigan, B Collura, C Iafrate, J Digumarthy, S Muzikansky, A Settleman, J Lynch, T Haber, D Toner, M AF Nagrath, Sunitha Maheswaran, Shyamala Sequist, Lecia Ulkus, Lindsey Brannigan, Brian Collura, Chey Iafrate, John Digumarthy, Subba Muzikansky, Alona Settleman, Jeffrey Lynch, Thomas Haber, Daniel Toner, Mehmet TI Blood biopsy on a microfluidic CTC-chip for non-invasive detection, monitoring and genotyping of tumors in lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Nagrath, Sunitha; Maheswaran, Shyamala; Sequist, Lecia; Ulkus, Lindsey; Brannigan, Brian; Collura, Chey; Iafrate, John; Digumarthy, Subba; Muzikansky, Alona; Settleman, Jeffrey; Lynch, Thomas; Haber, Daniel; Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4991 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603434 ER PT J AU Nanda, A Sander, D Fournier, L Singh, A Kachnic, L Settleman, J Willers, H AF Nanda, Akash Sander, David Fournier, Loreen Singh, Anurag Kachnic, Lisa Settleman, Jeffrey Willers, Henning TI The role of activating K-RAS mutation status in predicting radiosensitization to epidermal growth factor receptor (EGFR) inhibitors in non-small cell lung cancer (NSCLC) cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Radiat Oncol Program, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3962 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804024 ER PT J AU Neviani, P Santhanam, R Ma, YH Zhang, B Mao, HY Volinia, S Marcucci, G Chen, CS Cortes, J Huettner, C Koschmieder, S Hokland, P Bhatia, R Roy, D Caligiuri, M Perrotti, D AF Neviani, Paolo Santhanam, Ramasamy Ma, Yihui Zhang, Bin Mao, Hsiaoyin Volinia, Stefano Marcucci, Guido Chen, Ching-Shih Cortes, Jorge Huettner, Claudia Koschmieder, Steffen Hokland, Peter Bhatia, Ravi Roy, Denis Caligiuri, Michael Perrotti, Danilo TI PP2A induction by FTY720 inhibits survival and sel-renewal of CD34+/CD38-CML stem cell through the simultaneous suppression of BCR/ABL and BCR/ABL-independent signals. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Ferrara, I-44100 Ferrara, Italy. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Munster, D-48149 Munster, Germany. Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. Hop Maison Neuve Rosemont, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1075 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702603279 ER PT J AU Nosho, K Shima, K Irahara, N Kure, S Baba, Y Toyoda, S Kirkner, G Hazra, A Giovannucci, E Gokhale, S Li, C Jaenisch, R Fuchs, C Ogino, S AF Nosho, Katsuhiko Shima, Kaori Irahara, Natsumi Kure, Shoko Baba, Yoshifumi Toyoda, Saori Kirkner, Gregory Hazra, Aditi Giovannucci, Edward Gokhale, Sumita Li, Chen Jaenisch, Rudolf Fuchs, Charles Ogino, Shuji TI DNA methyltransferase-3B (DNMT3B) expression may contribute to CpG island methylator phenotype in colorectal cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Roger Williams Med Ctr, Dept Pathol, Providence, RI USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA USA. MIT, Dept Biol, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1316 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803059 ER PT J AU Nosho, K Irahara, N Shima, K Kure, S Baba, Y Toyoda, S Kirkner, G Schernhammer, E Hazra, A Hunter, D Quackenbush, J Spiegelman, D Giovannucci, E Fuchs, C Ogino, S AF Nosho, Katsuhiko Irahara, Natsumi Shima, Kaori Kure, Shoko Baba, Yoshifumi Toyoda, Saori Kirkner, Gregory Schernhammer, Eva Hazra, Aditi Hunter, David Quackenbush, John Spiegelman, Donna Giovannucci, Edward Fuchs, Charles Ogino, Shuji TI Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biostat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5187 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801443 ER PT J AU Ou, WB Fletcher, C Demetri, G Fletcher, J AF Ou, Wen-bin Fletcher, Christopher Demetri, George Fletcher, Jonathan TI Activated tyrosine kinases in gastrointestinal stromal tumor with loss of KIT oncoprotein expression SO CANCER RESEARCH LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1354 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802324 ER PT J AU Palanichamy, K Colman, H Chakravarti, A AF Palanichamy, Kamalakannan Colman, Howard Chakravarti, Arnab TI Brain tumor stem cell marker: Distinct populations of tumor-initiating cells expressing surface antigens derived from cancer stem cells mediates chemo and radio resistance SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1080 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603285 ER PT J AU Perry, J Hu, G Elledge, S Orkin, S AF Perry, Jennifer Hu, Guang Elledge, Stephen Orkin, Stuart TI Profiling essential genes in mouse osteosarcoma via genome-wide multiplex RNAi screening SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2584 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805193 ER PT J AU Petrovics, G Whitman, E Pomerantz, M Chen, YM Chamberlin, M Furusato, B Gao, CL Ali, A Hu, Y Ravindranath, L Dobi, A Sestrehenn, I McLeod, D Freedman, M Srivastava, S AF Petrovics, Gyorgy Whitman, Eric Pomerantz, Mark Chen, Youngmei Chamberlin, Michael Furusato, Bungo Gao, Chunling Ali, Amina Hu, Ying Ravindranath, Lakshmi Dobi, Albert Sestrehenn, Isabel McLeod, David Freedman, Matthew Srivastava, Shiv TI Prostate cancer risk allele specific for african descent correlates with pathologic stage at prostatectomy SO CANCER RESEARCH LA English DT Meeting Abstract C1 CPDR USU, Rockville, MD USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Dana Farber Canc Res Inst, Boston, MA USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3935 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703218 ER PT J AU Poage, G Christensen, B Marsit, C Houseman, EA Wrensch, M Karagas, M Yeh, RF Nelson, H Wiemels, J Zheng, SC Posner, M McClean, M Wiencke, J Kelsey, K AF Poage, Graham Christensen, Brock Marsit, Carmen Houseman, E. Andres Wrensch, Margaret Karagas, Margaret Yeh, Ru-Fang Nelson, Heather Wiemels, Joseph Zheng, Shichun Posner, Marshall McClean, Michael Wiencke, John Kelsey, Karl TI DNA methylation profiles are associated with specific genome-wide copy number alteration profiles in head and neck squamous cell carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 Brown Univ, Providence, RI 02912 USA. UCSF, San Francisco, CA USA. Dartmouth Med Sch, Lebenon, NH USA. Univ Minnesota, Minneapolis, MN USA. Dana Farber Canc Ctr, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1428 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803497 ER PT J AU Podar, K Zhang, J Tonon, G Sattler, M Grabher, C Lababidi, S Zimmerhackl, A Raab, M Vallet, S Zhou, YM Cartron, MA Tai, YT Chauhan, D Anderson, K AF Podar, Klaus Zhang, Jing Tonon, Giovanni Sattler, Martin Grabher, Clemens Lababidi, Samir Zimmerhackl, Alexander Raab, Marc Vallet, Sonia Zhou, Yiming Cartron, Marie-Astrid Tai, Yu-Tzu Chauhan, Dharminder Anderson, Kenneth TI Targeting angiogenesis via a c-Myc/Hif-1\#945;- dependent pathway in MM SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Rockville, MD 20857 USA. Massachussetts Gen Hosp, Boston, MA USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3185 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803478 ER PT J AU Podar, K Zimmerhackl, A Olson, D Tai, YT Hideshima, T Chauhan, D Anderson, K AF Podar, Klaus Zimmerhackl, Alexander Olson, Dian Tai, Yu-Tzu Hideshima, Teru Chauhan, Dharminder Anderson, Kenneth TI Potential therapeutic role of the selective adhesion molecule inhibitor natalizumab (Tysabri) in Multiple Myeloma SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Biogen Idec Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2236 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802422 ER PT J AU Polyak, K Shipitsin, M Campbell, L Hu, M AF Polyak, Kornelia Shipitsin, Michail Campbell, Lauren Hu, Min TI The role of the microenvironment in breast cancer progression SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Polyak, Kornelia; Shipitsin, Michail; Campbell, Lauren; Hu, Min] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA SY03-3 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800267 ER PT J AU Priolo, C Zadra, G Palescandolo, E Sicinska, E Loda, M AF Priolo, Carmen Zadra, Giorgia Palescandolo, Emanuele Sicinska, Ewa Loda, Massimo TI Unraveling the prostate cancer metabolome: Diagnostic and therapeutic implications SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-188 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803075 ER PT J AU Qi, J Rogers, A Christensen, J Janne, P Engelman, J AF Qi, Jie Rogers, Andrew Christensen, James Janne, Pasi Engelman, Jeffrey TI Mechanisms of resistance to MET inhibitors in MET-amplified gastric cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer, La Jolla, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3401 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802474 ER PT J AU Quackenbush, J Fan, JB Hirsch, M Mar, J Howe, E Holton, K Rubio, R April, C Chen, J Wickham-Garcia, E Liu, J Culhane, A Drapkin, R Matulonis, U AF Quackenbush, John Fan, Jian-Bing Hirsch, Michelle Mar, Jessica Howe, Eleanor Holton, Kristina Rubio, Renee April, Craig Chen, Jing Wickham-Garcia, Eliza Liu, Joyce Culhane, Aedin Drapkin, Ronny Matulonis, Ursula TI Molecular classification of serous ovarian cancer subtypes SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Illumina Inc, San Diego, CA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1441 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804012 ER PT J AU Reddy, M Fernandes, M Griffin, J Sattler, M AF Reddy, Mamatha Fernandes, Margret Griffin, James Sattler, Martin TI NADPH oxidases are not a major source of reactive oxygen species in myeloid leukemia cells transformed by oncogenic tyrosine kinases but are required for optimal cell growth SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Reddy, Mamatha; Fernandes, Margret; Griffin, James; Sattler, Martin] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-192 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803072 ER PT J AU Remillard, S Solomon, S Zhang, YX Demetri, G Wagner, A AF Remillard, Stephen Solomon, Sarah Zhang, Yixiang Demetri, George Wagner, Andrew TI Identification of genes affecting Apo2L/TRAIL sensitivity and resistance in an Apo2L/TRAIL resistant chondrosarcoma cell line SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Remillard, Stephen; Solomon, Sarah; Zhang, Yixiang; Demetri, George; Wagner, Andrew] HMS, Ludwig Canc Dana Farber Harvard, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5140 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702705212 ER PT J AU Rho, JH Roehrl, M Wang, J AF Rho, Jung-Hyun Roehrl, Michael Wang, Julia TI Glycoproteomic analysis of human lung adenocarcinomas using glycoarrays and tandem mass spectrometry: Differential expression and glycosylation patterns of vimentin and fetuin A isoforms SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4733 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701159 ER PT J AU Rho, JH Roehrl, M Wang, J AF Rho, Jung-hyun Roehrl, Michael Wang, Julia TI Tissue proteomics reveals differential and compartment-specific expression of the homologs transgeline and transgelin-2 in lung adenocarcinoma and its stroma SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3546 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701115 ER PT J AU Roccaro, A Sacco, A Chen, CZ Leleu, X Runnels, J Azab, AK Azab, F Jia, XY Ngo, H Melhem, M Varticovski, L Novina, C Rollins, B Anderson, K Ghobrial, I AF Roccaro, Aldo Sacco, Antonio Chen, Changzhong Leleu, Xavier Runnels, Judith Azab, Abdel Kareem Azab, Feda Jia, Xiaoying Ngo, Hai Melhem, Molly Varticovski, Lyuba Novina, Carl Rollins, Barrett Anderson, Kenneth Ghobrial, Irene TI MicroRNA in the biology, prognosis and therapy of Waldenstrom macroglobulinemia SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1393 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803205 ER PT J AU Roccaro, A Sacco, A Leleu, X Azab, AK Thompson, B Azab, F Jia, XY Ngo, H Runnels, J Melhem, M Fonseca, R Witzig, T Lin, C Anderson, K Ghobrial, I AF Roccaro, Aldo Sacco, Antonio Leleu, Xavier Azab, Abdel Kareem Thompson, Brian Azab, Feda Jia, Xiaoying Ngo, Hai Runnels, Judith Melhem, Molly Fonseca, Rafael Witzig, Thomas Lin, Charles Anderson, Kenneth Ghobrial, Irene TI microRNAs as regulators of multiple meyloma cells growth SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. Mayo Clin, Dept Hematol, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 568 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803106 ER PT J AU Rothenberg, S Rivera, M Winokur, D Settleman, J Haber, D AF Rothenberg, Stephen Rivera, Miguel Winokur, Daniel Settleman, Jeffrey Haber, Daniel TI Genome-wide analysis of causal genetic alterations in human cancer cell lines SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Rothenberg, Stephen; Rivera, Miguel; Winokur, Daniel; Settleman, Jeffrey; Haber, Daniel] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3344 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801269 ER PT J AU Roy, R Zurakowski, D Kulke, M Moses, M AF Roy, Roopali Zurakowski, David Kulke, Matthew Moses, Marsha TI Evaluation of urinary MMPs and TIMPs as potential biomarkers for pancreatic cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1583 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805108 ER PT J AU Sakamoto, H Friel, A Zukerberg, L Drapkin, R Rueda, B AF Sakamoto, Hideo Friel, Anne Zukerberg, Lawrence Drapkin, Ronny Rueda, Bo TI Cables 1 knockdown in immortalized human ovarian surface epithelial cells results in their uptake of more malignant like characteristics SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2266 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803176 ER PT J AU Sanchez, C Sahin, A Palanichamy, K Waterman, P Chakravarti, A Weissleder, R Morse, B Carvajal, I Marsh, N Furfine, E Carter, B AF Sanchez, Carlos Sahin, Ayguen Palanichamy, Kamalakannan Waterman, Peter Chakravarti, Arnab Weissleder, Ralph Morse, Brent Carvajal, Irvith Marsh, Nick Furfine, Eric Carter, Bob TI Combination of the anti-angiogenic Adnectin (TM) BMS-844203 (CT-322) and Temozolomide provides a survival advantage in an intracanial glioblastoma model SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Adnexus, Waltham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-286 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702602460 ER PT J AU Sasada, T Zeng, WY Kang, YJ Zhang, ZP Mizukami, Y Choi, J Brusic, V Reinherz, E AF Sasada, Tetsuro Zeng, Wanyong Kang, Yoon Joong Zhang, Zhiping Mizukami, Yo Choi, Jaewon Brusic, Vladimir Reinherz, Ellis TI Maternal embryonic leucine zipper kinase, MELK, encodes novel cytotoxic T lymphocyte (CTL) epitopes capable of inducing HLA-A*0201-restricted and tumor-reactive CTLs SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Sasada, Tetsuro; Zeng, Wanyong; Kang, Yoon Joong; Zhang, Zhiping; Mizukami, Yo; Choi, Jaewon; Brusic, Vladimir; Reinherz, Ellis] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4176 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804367 ER PT J AU Sasajima, J Mizukami, Y Nakamura, K Sugiyama, Y Yamazaki, M Sato, K Fujiya, M Kawabe, J Tanno, S Okumura, T Kono, T Ii, M Bardeesy, N Chung, D Kohgo, Y AF Sasajima, Junpei Mizukami, Yusuke Nakamura, Kazumasa Sugiyama, Yoshiaki Yamazaki, Madoka Sato, Kazuya Fujiya, Mikihiro Kawabe, Jun-ichi Tanno, Satoshi Okumura, Toshikatsu Kono, Toru Ii, Masaaki Bardeesy, Nabeel Chung, Daniel Kohgo, Yutaka TI The tumor vasculature is a paracrine target of Hedgehog in pancreatic cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Asahikawa Med Coll, Asahikawa, Hokkaido 078, Japan. Inst Biomed Res & Innovat, Kobe, Hyogo, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2004 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803083 ER PT J AU Schernhammer, E Giovannuccci, E Kawasaki, T Rosner, B Fuchs, C Ogino, S AF Schernhammer, Eva Giovannuccci, Edward Kawasaki, Takako Rosner, Bernard Fuchs, Charles Ogino, Shuji TI A prospective study of dietary folate and vitamin B in relation to LINE-1 hypomethylation in colon cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5183 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801439 ER PT J AU Scholl, C Frohling, S Dunn, I Schinzel, A Barbie, D Kim, S Silver, S Tamayo, P Wadlow, R Ramaswamy, S Dohner, K Bullinger, L Sandy, P Boehm, J Root, D Jacks, T Hahn, W Gilliland, D AF Scholl, Claudia Frohling, Stefan Dunn, Ian Schinzel, Anna Barbie, David Kim, So Silver, Serena Tamayo, Pablo Wadlow, Raymond Ramaswamy, Sridhar Dohner, Konstanze Bullinger, Lars Sandy, Peter Boehm, Jesse Root, David Jacks, Tyler Hahn, William Gilliland, D. TI Synthetic lethal interaction between oncogenic KRAS dependency and suppression of STK33 in human cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Broad Inst Harvard & MIT, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Hosp Ulm, Ulm, Germany. David H Koch Inst Integrat Canc Res, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5608 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802111 ER PT J AU Shimamura, T Borgman, C Chen, L Li, DN Foley, K Sang, J Meyerson, M Ying, WW Barsoum, J Wong, KK Shapiro, G AF Shimamura, Takeshi Borgman, Christa Chen, Liang Li, Danan Foley, Kevin Sang, Jim Meyerson, Matthew Ying, Weiwen Barsoum, James Wong, Kwok-Kin Shapiro, Geoffrey TI The novel Hsp90 inhibitor STA-9090 has potent anticancer activity in in vitro and in vivo models of lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Synta Pharmaceut Corp, Lexington, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4679 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604287 ER PT J AU Silva, A Bodyak, N Sauer, N Vaze, M Laroux, S Harborth, J Li, C Fruehauf, J AF Silva, Alison Bodyak, Natalya Sauer, Noel Vaze, Moru Laroux, Stephen Harborth, Jens Li, Chiang Fruehauf, Johannes TI Safety and Efficacy of a tkRNAi Therapeutic Targeting beta-catenin (CTNNBI) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Cequent Pharma, Cambridge, MA USA. Harvard Univ, Skip Ackerman Ctr Mol Therapeut, BIDMC, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-123 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805427 ER PT J AU Singh, A Greninger, P Rhodes, D Koopman, L Violette, S Bardeesy, N Settleman, J AF Singh, Anurag Greninger, Patricia Rhodes, Daniel Koopman, Louise Violette, Sheila Bardeesy, Nabeel Settleman, Jeffrey TI A gene expression signature associated with \#8220;K-Ras addiction\#8221; reveals novel candidate therapeutic targets that regulate EMT SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. Biogen Idec Inc, Cambridge, MA USA. Stromedix, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1882 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805007 ER PT J AU Skog, J Wurdinger, T Lessard, R Balaj, L Carter, B Hochberg, F Breakefield, X AF Skog, Johan Wurdinger, Thomas Lessard, Ryan Balaj, Leonora Carter, Bob Hochberg, Fred Breakefield, Xandra TI Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. VU Canc Ctr, Amsterdam, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-98 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803267 ER PT J AU Smits, M Mir, S Niers, J Marquez, V Tannous, B Cloos, J Noske, D Wurdinger, T AF Smits, Michiel Mir, Shahryar Niers, Johanna Marquez, Victor Tannous, Bakhos Cloos, Jacqueline Noske, David Wurdinger, Tom TI MicroRNA-101 targets EZH2 and controls angiogenesis in glioblastoma multiforme SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4761 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804254 ER PT J AU Sorensen, AG Batchelor, T Ancukiewicz, M Zhang, WT Chen, PJ Yeo, P Wang, MY Jennings, D Wen, P Landenranta, J di Tomaso, E Duda, D Jain, R AF Sorensen, A. Gregory Batchelor, Tracy Ancukiewicz, Marek Zhang, Wei-Ting Chen, Poe-Jou Yeo, Priscilla Wang, Meiyun Jennings, Dominique Wen, Patrick Landenranta, Johanna di Tomaso, Emmanuelle Duda, Dan Jain, Rakesh TI A \#8220;vascular normalization index\#8221; as a mechanistic biomarker to predict survival after a single dose of cediranib in recurrent glioblastoma patients: Insights from a Phase II study SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-94 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805062 ER PT J AU Stegmaier, K AF Stegmaier, Kimberly TI Gene expression-based approaches to small molecule discovery for cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Stegmaier, Kimberly] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA SY08-2 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701800278 ER PT J AU Straume, O Shimamura, T Oyan, A Lampa, M Borgman, C Short, S Soo-Young, K Randolph, W Chen, L Collet, K Wong, KK Sharpio, G Kalland, K Folkman, J Akslen, L Naumov, G AF Straume, Oddbjorn Shimamura, Takeshi Oyan, Anne Lampa, Michael Borgman, Christa Short, Sarah Soo-Young, Kang Randolph, Watnick Chen, Liang Collet, Karin Wong, Kwok-Kin Sharpio, Geoffrey Kalland, Karl Folkman, Judah Akslen, Lars Naumov, George TI Suppression of heat shock Protein 27 induces long-term dormancy in human breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Haukeland Hosp, N-5021 Bergen, Norway. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Gade Inst, Bergen, Norway. Harvard Univ, Sch Med, Dept Surg, Childrens Hosp, Boston, MA 02115 USA. RI Kalland, Karl-Henning/B-9445-2017; Akslen, Lars /C-1202-2017; Straume, Oddbjorn/C-2186-2017 OI Kalland, Karl-Henning/0000-0003-4486-2334; Akslen, Lars /0000-0003-2710-9543; Straume, Oddbjorn/0000-0001-8867-3645 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 159 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603017 ER PT J AU Tai, YT Soydan, E Fulciniti, M Song, WH Kim, K Hong, FX Li, XF Burger, P Rumizen, MJ Nahar, S Podar, K Chauhan, D Hideshima, T Munshi, N Tonon, G Carrasco, R Anderson, K AF Tai, Yu-Tzu Soydan, Ender Fulciniti, Mariateresa Song, Weihua Kim, Kihyun Hong, Fangxin Li, Xian-Feng Burger, Peter Rumizen, Mathew J. Nahar, Sabikun Podar, Klaus Chauhan, Dharminder Hideshima, Teru Munshi, Nikhil Tonon, Giovanni Carrasco, Ruben Anderson, Kenneth TI CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated interactions with bone marrow stromal cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Tai, Yu-Tzu; Soydan, Ender; Fulciniti, Mariateresa; Song, Weihua; Kim, Kihyun; Hong, Fangxin; Li, Xian-Feng; Burger, Peter; Rumizen, Mathew J.; Nahar, Sabikun; Podar, Klaus; Chauhan, Dharminder; Hideshima, Teru; Munshi, Nikhil; Tonon, Giovanni; Carrasco, Ruben; Anderson, Kenneth] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 325 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804185 ER PT J AU Tai, YT Kim, K Fulciniti, M Soydan, E Song, WH Li, XF Rumizen, M Nahar, S Burger, P Hideshima, T Richardson, P Munshi, N Clark, A Goutopoulos, A Rastelli, L Kenneth, K AF Tai, Yu-Tzu Kim, Kihyun Fulciniti, Mariateresa Soydan, Ender Song, Weihua Li, Xian-Feng Rumizen, Matthew Nahar, Sabikun Burger, Peter Hideshima, Teru Richardson, Paul Munshi, Nikhil Clark, Ann Goutopoulos, Andreas Rastelli, Luca Kenneth, Kenneth TI Targeting MEK1/2 signaking cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol,Dept Med, Soul, South Korea. EMD Serono Res Inst, Rockland, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3695 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702706008 ER PT J AU Ter-Minassian, M Wang, ZX Asomaning, K Wu, M Liu, CY Su, L Frauenhoffer, C Hooshmand, S Silver, J Lin, XH Christiani, D Kulke, M AF Ter-Minassian, Monica Wang, Zhaoxi Asomaning, Kofi Wu, Michael Liu, Chen-Yu Su, Li Frauenhoffer, Christine Hooshmand, Susanne Silver, Jamie Lin, Xihong Christiani, David Kulke, Matthew TI Association of a TSC2 SNP with sporadic neuroendocrine tumor risk SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3050 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703258 ER PT J AU Thomas, R Sos, M Meyerson, M Wong, K Peifer, M Weiss, J Zander, T Fischer, S AF Thomas, Roman Sos, Martin Meyerson, Matthew Wong, Kwok Peifer, Martin Weiss, Jonathan Zander, Thomas Fischer, Stefanie TI A functional genomics approach for prediction of drug activity in non-small cell lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Max Planck Inst Neurol Res, D-50931 Cologne, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany. Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2587 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804027 ER PT J AU Tobi, M Gupta, R Irwin, B Hatfield, J Jung, HS Edgar, BJ Kim, M Rodriguez, R Kim, J AF Tobi, Martin Gupta, Rasna Irwin, Bradley Hatfield, James Jung, Han Sue Edgar, Ben Josef Kim, Mijin Rodriguez, Rebecca Kim, Jyung TI Vascular mimicry may explain high baseline rectal VEGF: A potential mechanism of chronic radiation proctitis in prostate cancer patients. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. VAMC, Detroit, MI USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3625 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702231 ER PT J AU Tsukada, K Conner, D Lin, QC Kucherlapati, R Jain, R Fukumura, D AF Tsukada, Kosuke Conner, David Lin, Qingcong Kucherlapati, Raju Jain, Rakesh Fukumura, Dai TI Blockade of inducible nitric oxide synthase normalizes murine breast cancer vessels SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4038 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803354 ER PT J AU Turke, A Song, Y Lindeman, N Lifshits, E Xiao, Y Lee, C Janne, P Engelman, J AF Turke, Alexa Song, Youngchul Lindeman, Neal Lifshits, Eugene Xiao, Yun Lee, Charles Janne, Pasi Engelman, Jeffrey TI HGF induces transient and stable ligand-independent resistance in gefitinib-sensitive lung cancers SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mass Gen Hosp, Ctr Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1365 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802337 ER PT J AU Tworoger, S Rice, M Belsley, N Collins, L Clevenger, C Hankinson, S AF Tworoger, Shelley Rice, Megan Belsley, Nichole Collins, Laura Clevenger, Charles Hankinson, Susan TI Risk of breast cancer with plasma prolactin concentrations by prolactin staining in the tumor SO CANCER RESEARCH LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Beth Isreal Deaconess Med Ctr, Boston, MA USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-230 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703166 ER PT J AU Vallet, S Vaghela, N Fulciniti, M Veiby, P Patel, K Hideshima, T Pozzi, S Santo, L Mukherjee, S Cirstea, D Scadden, D Anderson, K Noopur, R AF Vallet, Sonia Vaghela, Nileshwari Fulciniti, MariaTeresa Veiby, Petter Patel, Kishan Hideshima, Teru Pozzi, Samantha Santo, Loredana Mukherjee, Siddhartha Cirstea, Diana Scadden, David Anderson, Kenneth Noopur, Raje TI The CCR1 inhibitor, MLN3897, enhances Velcade inhibition of multiple myeloma (MM)-bone cells interactions SO CANCER RESEARCH LA English DT Meeting Abstract C1 MGH, Canc Res, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 318 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804422 ER PT J AU Vasudevan, K Barbie, D Davies, M Rabinovsky, R Hennessy, B Tseng, H Pochanard, P Kim, SY Dunn, I Schinzel, A McNear, C Kim, J Boehm, J Silver, S Lu, YL Stemke-Hale, K Dutta, B Joy, C Sahin, A Gonzalez-Angulo, AM Lluch, A Rameh, L Jacks, T Root, D Lander, E Mills, G Hahn, W Sellers, W Garraway, L AF Vasudevan, Krishna Barbie, David Davies, Michael Rabinovsky, Rosalia Hennessy, Bryan Tseng, Hsiuyi Pochanard, Panisa Kim, So Young Dunn, Ian Schinzel, Anna McNear, Chontelle Kim, Jessica Boehm, Jesse Silver, Serena Lu, Yiling Stemke-Hale, Katherine Dutta, Bhaskar Joy, Corwin Sahin, Aysegul Maria Gonzalez-Angulo, Ana Lluch, Ana Rameh, Lucia Jacks, Tyler Root, David Lander, Eric Mills, Gordon Hahn, William Sellers, William Garraway, Levi TI PDK1-SGK3 signaling in the absence of AKT activation in PIK3CA- mutant cancers SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Broad Inst MIT & Harvard, Cambridge, MA USA. Univ Valencia, Clin Hosp, Valencia, Spain. Boston Biomed Res Inst, Watertown, MA USA. MIT, Cambridge, MA 02139 USA. Novartis Inst Biomed Res, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3822 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801250 ER PT J AU Wang, HB Zhao, AL Chen, L Liao, J Zhong, XY Li, J Chowdhury, D Pfeifer, G Yen, Y Xu, XZ AF Wang, Haibo Zhao, Ailian Chen, Lin Liao, Ji Zhong, Xueyan Li, Jing Chowdhury, Dipanjan Pfeifer, Gerd Yen, Yun Xu, Xingzhi TI Human RIF1 encodes an anti-apoptotic factor required for DNA repair SO CANCER RESEARCH LA English DT Meeting Abstract C1 Capital Normal Univ, Beijing, Peoples R China. Peking Univ, Sch Clin Oncol, Beijing 100871, Peoples R China. City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 475 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801355 ER PT J AU Weinstein, J Donehower, L Aldape, K Meyerson, M Chin, L Schultz, N Yung, A Sander, C Wheeler, D AF Weinstein, John Donehower, Lawrence Aldape, Kenneth Meyerson, Matthew Chin, Lynda Schultz, Nikolaus Yung, Alfred Sander, Chris Wheeler, David TI Analyzing the TCGA glioblastoma samples: Co-occurrence and mutual exclusivity of gene aberrations in the key p53, Rb, and RTK pathways SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Broad Inst, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2450 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801046 ER PT J AU Wetherill, Y Ficarro, S Xian, W Brugge, J Hankinson, S Tamimi, R Freedman, M Marto, J Iglehart, JD Miron, A AF Wetherill, Yelena Ficarro, Scott Xian, Wa Brugge, Joan Hankinson, Susan Tamimi, Rulla Freedman, Matthew Marto, Jarrod Iglehart, J. Dirk Miron, Alexander TI Understanding breast cancer risk conferred by FGFR2 single nucleotide polymorphisms SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 99 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704049 ER PT J AU White, R Burke, C Cech, J Sessa, A Datta, S Long, H Ratanasirintrawoot, S Chen, F Zon, L AF White, Richard Burke, Christopher Cech, Jennifer Sessa, Anna Datta, Sumon Long, Hannah Ratanasirintrawoot, Sutheera Chen, Frank Zon, Leonard TI Zebrafish chemical genetics identifies lineage-specific tumor inhibitors SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Worcester, MA 01605 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Texas Austin, Austin, TX 78712 USA. Univ Cambridge, Cambridge, England. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3115 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803404 ER PT J AU Whitehurst, A Purinton, S Roland, C Brekken, R Xie, Y Schorge, J White, M AF Whitehurst, Angelique Purinton, Scott Roland, Crisy Brekken, Rolf Xie, Yang Schorge, John White, Michael TI Employing functional genomics to reveal emergent dependencies supporting tumorigenic regulatory networks SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5607 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802110 ER PT J AU Wong, HKA Landenranta, J Chan, A Plotkin, S McClatchy, A Jain, R Di Tomaso, E AF Wong, Hon-Kit Andus Landenranta, Johanna Chan, Annie Plotkin, Scott McClatchy, Andrea Jain, Rakesh Di Tomaso, Emmanuelle TI Inhibition of the VEGF pathway can alleviate growth of NF2-associated schwannomas SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wong, Hon-Kit Andus; Landenranta, Johanna; Chan, Annie; Plotkin, Scott; McClatchy, Andrea; Jain, Rakesh; Di Tomaso, Emmanuelle] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4070 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804214 ER PT J AU Wu, P Wang, Q Chu, E Wu, D AF Wu, Peter Wang, Qin Chu, Elizabeth Wu, Daniel TI Telomere dysfunction reinforces therapy-induced cellular senescence SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wu, Peter; Wang, Qin; Chu, Elizabeth; Wu, Daniel] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3471 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804088 ER PT J AU Yamamoto, S Sato, T Hasegawa, Y Sato, H Ishigaki, M Suganuma, M Kufe, D VonHoff, D Kawabe, T AF Yamamoto, Sayaka Sato, Takuji Hasegawa, Yoko Sato, Hitoshi Ishigaki, Machiyo Suganuma, Masashi Kufe, Donald VonHoff, Daniel Kawabe, Takumi TI CBP501 increases DNA damage induced by bleomycin and cisplatin SO CANCER RESEARCH LA English DT Meeting Abstract C1 CanBas Co Ltd, Numazu, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1823 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604279 ER PT J AU Yanagawa, J Walser, T Zhu, L Luo, J Hong, LS Fishbein, M Goodglick, L Strieter, R Sharma, S Dubinett, S AF Yanagawa, Jane Walser, Tonya Zhu, Li Luo, Jie Hong, Longsheng Fishbein, Michael Goodglick, Lee Strieter, Robert Sharma, Sherven Dubinett, Steven TI The zinc-finger E-box-binding transcriptional repressor Snail promotes CXCR2 ligand dependent tumor progression in non-small cell lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Hlth Care Ctr, Los Angeles, CA USA. Univ Virginia, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1527 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804327 ER PT J AU Yang, CW Li, CQ Sgroi, D Schmidt, E AF Yang, Chuanwei Li, Cuiqi Sgroi, Dennis Schmidt, Emmett TI Cyclin D1 promotes progesterone receptor signaling SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5038 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800110 ER PT J AU Yang, YX Shields, H Fruehauf, J Guo, HN Keates, AC Upton, M LaMont, JT Li, CJ AF Yang, Youxin Shields, Helen Fruehauf, Johannes Guo, Hongnian Keates, Andrew C. Upton, Melissa LaMont, J. Thomas Li, Chiang J. TI Expression of putative intestinal stem cell marker GPR49 and genomic instability in Barrett\#8217;s esophagus and associated adenocarcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yang, Youxin; Shields, Helen; Fruehauf, Johannes; Guo, Hongnian; Keates, Andrew C.; Upton, Melissa; LaMont, J. Thomas; Li, Chiang J.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1653 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702013 ER PT J AU Yoda, A Bar-Natan, M Sattler, M Ritz, J Frank, D Weinstock, D AF Yoda, Akinori Bar-Natan, Michal Sattler, Martin Ritz, Jerome Frank, David Weinstock, David TI CRLF2 is a proto-oncogene in pre-B acute lymphoblastic leukemia with normal cytogenetics SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yoda, Akinori; Bar-Natan, Michal; Sattler, Martin; Ritz, Jerome; Frank, David; Weinstock, David] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5610 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802113 ER PT J AU Yoon, H Powell, M Gibson, M Montgomery, E Hafez, M Catalano, P Liu, G Skaar, T Dolan, M Wu, XF Diasio, R Forastiere, A Benson, A Kleinberg, L Murphy, K AF Yoon, Harry Powell, Mark Gibson, Michael Montgomery, Elizabeth Hafez, Michael Catalano, Paul Liu, Geoffrey Skaar, Todd Dolan, M. Wu, Xifeng Diasio, Robert Forastiere, Arlene Benson, Al Kleinberg, Lawrence Murphy, Kathleen TI Outcome prediction based on genetic polymorphisms (GPs) in epidermal growth factor (EGF) pathway in patients (pts) with esophageal adenocarcinoma (EAC) treated with preoperative (preop) cisplatin (C)-based chemoradiation (CRT): Results from the Eastern Cooperative Oncology Group (ECOG) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA USA. Johns Hopkins Univ, Baltimore, MD USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Indiana Univ, Indianapolis, IN 46204 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1621 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805159 ER PT J AU Yu, J Kane, S Li, DG Benedettini, E Haack, H Smith, B Gu, TL Loda, M Zhou, XM Comb, M AF Yu, Jian Kane, Susan Li, Daigiang Benedettini, Elisa Haack, Herbert Smith, Bradly Gu, Tinglei Loda, Massimo Zhou, Xinmine Comb, Michael TI Mutation-specific antibodies for the detection of EGFR mutation in non-small-cell lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Cell Signal Technol, Danvers, MA USA. Cent S Univ, Xiangya Hosp 2, Changsha, Hunan, Peoples R China. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5387 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803349 ER PT J AU Zadra, G Fedele, G Photopoulos, C Zamponi, R Priolo, C Rose, J Birnberg, N Loda, M AF Zadra, Giorgia Fedele, Giuseppe Photopoulos, Cornelia Zamponi, Raffaella Priolo, Carmen Rose, Joshua Birnberg, Neal Loda, Massimo TI AMP-activated protein kinase (AMPK) activation reduces prostate tumor cell growth via inhibition of fatty acid synthase SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mercury Therapeut Inc, Woburg, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4411 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804164 ER PT J AU Zejnullahu, K Song, YC Lifshits, E Toschi, L Rogers, A Murphy, C Xiao, Y Lee, C Christensen, J Engelman, J Janne, P AF Zejnullahu, Kreshnik Song, Young Chul Lifshits, Eugene Toschi, Luca Rogers, Andrew Murphy, Carly Xiao, Yun Lee, Charles Christensen, James Engelman, Jeffrey Janne, Pasi TI MET amplification leads to resistance to the irreversible EGFR inhibitor PF00299804 through selection of a pre-existing MET amplified clone SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Bosston, MA USA. Pfizer Inc, Groton, CT 06340 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3874 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604362 ER PT J AU Zha, S Li, G Cheng, HL Brush, J Patel, H Goff, P Alt, F AF Zha, Shan Li, Gang Cheng, Hwei-Ling Brush, James Patel, Harin Goff, Peter Alt, Frederick TI ATM and XLF/Cernunnos synergize in DNA repair during V(D)J recombination SO CANCER RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 453 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801331 ER PT J AU Zhai, RH Chen, F Liu, G Su, L Asomaning, K Lynch, T Wain, J Christiani, D AF Zhai, Rihong Chen, Feng Liu, Geoffrey Su, Li Asomaning, Kofi Lynch, Thomas Wain, John Christiani, David TI Interactions among BMI, smoking, and genetic variants of apoptosis pathway genes in esophageal adenocarcinoma risk SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Toronta, Toronto, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2107 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703184 ER PT J AU Zhang, L Farrell, J Sugimoto, M Hirayama, A Soga, T Zhou, H Elashoff, D Gao, K Paster, B Tomita, M Wong, D AF Zhang, Lei Farrell, James Sugimoto, Masahiro Hirayama, Akiyoshi Soga, Tomoyoshi Zhou, Hui Elashoff, David Gao, Kai Paster, Bruce Tomita, Masaru Wong, David TI Saliva biomarkers for pancreatic cancer detection SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. Keio Univ, Inst Adv Biosci, Tsuroka, Japan. Keio Univ, Adv Biosci 3Inst, Tsuroka, Japan. Human Metabolome Technol Inc, Tsuroka, Japan. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1898 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702463 ER PT J AU Zhang, M Siedow, M Saia, G Chakravarti, A AF Zhang, Min Siedow, Michael Saia, Gregory Chakravarti, Arnab TI A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the p21-activated kinase 6 (PAK6) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Generla Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-101 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802123 ER PT J AU Zhang, M Siedow, M Saia, G Chakravarti, A AF Zhang, Min Siedow, Michael Saia, Gregory Chakravarti, Arnab TI Inhibition of p21-activated kinase 6 (PAK6) increases radiosensitivity of prostate cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Zhang, Min; Siedow, Michael; Saia, Gregory; Chakravarti, Arnab] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3977 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804037 ER PT J AU Zhang, M Coen, J Siedow, M Bermudez, RS Suzuki, Y Chakravarti, A AF Zhang, Min Coen, John Siedow, Michael Bermudez, R. Scott Suzuki, Yoshiyuki Chakravarti, Arnab TI Survivin expression is associated with prostate cancer metastasis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Zhang, Min; Coen, John; Siedow, Michael; Bermudez, R. Scott; Suzuki, Yoshiyuki; Chakravarti, Arnab] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1046 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603085 ER PT J AU Zhang, YX Remillard, S Demetri, G Wagner, A AF Zhang, Yixiang Remillard, Stephen Demetri, George Wagner, Andrew TI Functional profiling of receptor tyrosine kinases (RTKs) and downstream signaling pathways in chondrosarcomas: Rational foundation for targeted therapy SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Zhang, Yixiang; Remillard, Stephen; Demetri, George; Wagner, Andrew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ludwig Ctr Dana Farber Harvard, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2843 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802037 ER PT J AU Zurita, A Wu, HK Lin, E Kulke, M Tye, L Bello, C DePrimo, S McKee, K Heymach, J AF Zurita, Amado Wu, Hua-Kang Lin, E. Kulke, Matthew Tye, Lesley Bello, Carlo DePrimo, Samuel McKee, Kathryn Heymach, John TI Sunitinib (SU) affects specific peripheral blood mononuclear cell subpopulations (PBMC) and circulating endothelial cells (CEC) in patients (pts) with neuroendocrine tumors (NET): correlation with plasma proteins and pharmacokinetics SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Global Res & Dev, La Jolla, CA USA. Pfizer Global Res & Dev, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-284 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702602458 ER PT J AU Bradbury, PA Zhai, RH Hopkins, J Kulke, MH Heist, RS Singh, S Zhou, W Ma, C Xu, W Asomaning, K Ter-Minassian, M Wang, ZX Su, L Christiani, DC Liu, G AF Bradbury, Penelope A. Zhai, Rihong Hopkins, Jessica Kulke, Matthew H. Heist, Rebecca S. Singh, Simron Zhou, Wei Ma, Clement Xu, Wei Asomaning, Kofi Ter-Minassian, Monica Wang, Zhaoxi Su, Li Christiani, David C. Liu, Geoffrey TI Matrix metalloproteinase 1, 3 and 12 polymorphisms and esophageal adenocarcinoma risk and prognosis SO CARCINOGENESIS LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISM; LUNG-CANCER; BARRETTS-ESOPHAGUS; PROMOTER; PROGRESSION; GENES; MATRIX-METALLOPROTEINASE-9; EXPRESSION; CARCINOMA; GENOTYPES AB The matrix metalloproteinase (MMP) family degrade extracellular matrix and mediate pathways including apoptosis, angiogenesis and immunity. We studied the association between four MMP polymorphisms within three MMP genes and esophageal adenocarcinoma (EA) risk and prognosis. A total of 313 EA cases and 455 age and gender frequency-matched controls were genotyped for MMP1 1G/2G, MMP3 6A/5A, MMP12 -82A/G and MMP12 1082A/G. The association between individual MMP polymorphisms and EA risk was evaluated using regression models and adjusted for age, gender, adult body mass index and smoking status. Haplotype analysis was performed to investigate the combined effect of all four linked MMP polymorphisms and EA risk. The MMP1 and MMP3 polymorphisms were associated with increased EA risk: MMP1 1G/2G and 2G/2G had adjusted odds ratios of 1.46 [95% confidence interval 1.0-2.1; P = 0.04] and adjusted odds ratio 1.83 (1.2-2.8; P = 0.005), respectively, whereas MMP3 6A/5A had adjusted odds ratio 1.40 (95% confidence interval 1.0-2.1; P = 0.09) and MMP3 5A/5A had 1.61 (95% confidence interval 1.0-2.5; P = 0.03). Two MMP haplotypes [MMP1-MMP3-MMP12 (-82) 2G-5A-A (adjusted odds ratio 1.36, 95% confidence interval 1.0-1.8; P = 0.03) and 2G-5A-G (adjusted odds ratio 1.70, 95% confidence interval 1.1-2.6; P = 0.01)] were also associated with increased EA risk. The relationship between BE cases with the same set of controls was similar. No association was identified between the MMP polymorphisms and overall survival or progression free survival of patients with EA. MMP1, MMP3 and possibly MMP12 -82A/G polymorphisms and their haplotypes are associated with increased EA risk. C1 [Liu, Geoffrey] Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. [Bradbury, Penelope A.; Hopkins, Jessica; Ma, Clement; Xu, Wei; Liu, Geoffrey] Dalla Lama Sch Publ Hlth, Dept Med, Toronto, ON M5G 2M9, Canada. [Bradbury, Penelope A.; Hopkins, Jessica; Ma, Clement; Xu, Wei; Liu, Geoffrey] Dalla Lama Sch Publ Hlth, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. [Bradbury, Penelope A.; Hopkins, Jessica; Ma, Clement; Xu, Wei; Liu, Geoffrey] Dalla Lama Sch Publ Hlth, Dept Biostat & Epidemiol, Toronto, ON M5G 2M9, Canada. [Bradbury, Penelope A.; Hopkins, Jessica; Ma, Clement; Xu, Wei; Liu, Geoffrey] Univ Toronto, Toronto, ON M5G 2M9, Canada. [Zhai, Rihong; Heist, Rebecca S.; Zhou, Wei; Asomaning, Kofi; Ter-Minassian, Monica; Wang, Zhaoxi; Su, Li; Christiani, David C.; Liu, Geoffrey] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Heist, Rebecca S.; Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singh, Simron] Toronto Sunnybrook Reg Canc Ctr, Toronto, ON M4N 3M5, Canada. [Liu, Geoffrey] Ontario Canc Inst, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. RP Liu, G (reprint author), Princess Margaret Hosp, Ontario Canc Inst, 610 Univ Ave,Suite 7-124, Toronto, ON M5G 2M9, Canada. EM geoffrey.liu@uhn.on.ca RI Liu, Geoffrey/N-4421-2016 FU National Institutes of Health [R01 CA074386]; Doris Duke Charitable Foundation; Alan B. Brown Chair in Molecular Genomics; Posluns Family; Princess Margaret Foundations; Canadian Institutes of Health Research; Flight Attendant Medical Research Institute FX National Institutes of Health (R01 CA074386); Doris Duke Charitable Foundation; Alan B. Brown Chair in Molecular Genomics; Posluns Family; Princess Margaret Foundations; Canadian Institutes of Health Research; Flight Attendant Medical Research Institute young investigator award. NR 27 TC 27 Z9 28 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2009 VL 30 IS 5 BP 793 EP 798 DI 10.1093/carcin/bgp065 PG 6 WC Oncology SC Oncology GA 441AB UT WOS:000265740000011 PM 19321798 ER PT J AU Panchenko, MP Silva, N Stone, JR AF Panchenko, Mikhail P. Silva, Nilsa Stone, James R. TI Up-regulation of a hydrogen peroxide-responsive pre-mRNA binding protein in atherosclerosis and intimal hyperplasia SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE Heterogeneous nuclear ribonucleoprotein C; Hydrogen peroxide; H(2)O(2); Intimal hyperplasia; Neointima; Vascular smooth muscle; Vascular cell activation; Atherosclerosis ID SMOOTH-MUSCLE-CELLS; NUCLEAR RIBONUCLEOPROTEIN C1/C2; AMERICAN-HEART-ASSOCIATION; HUMAN CORONARY-ARTERY; HNRNP C; PHYSIOLOGICAL LEVELS; ENDOTHELIAL-CELLS; VASCULAR-LESIONS; NADPH OXIDASE; TRANSLATION AB Background: Multiple lines of investigation have implicated hydrogen peroxide (H(2)O(2)) as an important endogenous mediator of cell proliferation in the vessel wall. Heterogeneous nuclear ribonucleoprotein C (hnRNP-C), a nuclear pre-mRNA binding protein that plays roles in vertebrate cell proliferation and differentiation, has been identified as a component of a vascular cell signaling pathway activated by low physiologic levels of H(2)O(2). The expression of hnRNP-C in human arteries has not previously been assessed. Methods: Segments of human proximal internal carotid arteries were evaluated for the expression of hnRNP-C by immunohistochemistry. Results: In normal proximal internal carotid arteries, hnRNP-C is expressed predominantly by the endothelium, with significantly lower expression by medial smooth muscle. In preatherosclerotic intimal hyperplasia, hnRNP-C is up-regulated in the artery wall, due to the robust expression by the intimal smooth muscle cells, without up-regulation in the medial smooth muscle cells. In arteries with atherosclerotic lesions, there is strong expression of hnRNP-C not only by intimal cells but also by medial smooth muscle cells. Conclusions: The H(2)O(2) responsive pre-mRNA binding protein hnRNP-C is up-regulated in atherosclerosis and in preatherosclerotic intimal hyperplasia in humans, supporting the hypothesis that H(2)O(2) is a regulator of vascular cell proliferation in these conditions. These data also suggest that hnRNP-C may be useful as a marker of vascular cell activation. (C) 2009 Elsevier Inc. All rights reserved. C1 [Stone, James R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Stone, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Simches Res Bldg Room 8236,185 Cambridge St CPZN, Boston, MA 02114 USA. EM jrstone@partners.org FU NIH [HL074324] FX This work was supported by NIH Grant HL074324. NR 38 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD MAY-JUN PY 2009 VL 18 IS 3 BP 167 EP 172 DI 10.1016/j.carpath.2008.03.008 PG 6 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 445NF UT WOS:000266056800006 PM 18508286 ER PT J AU Moussa, ID Jaff, MR Mehran, R Gray, W Dangas, G Lazic, Z Moses, JW AF Moussa, Issam D. Jaff, Michael R. Mehran, Roxana Gray, William Dangas, George Lazic, Zoran Moses, Jeffery W. TI Prevalence and Prediction of Previously Unrecognized Peripheral Arterial Disease in Patients With Coronary Artery Disease: The Peripheral Arterial Disease in Interventional Patients Study SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE PVD-peripheral disease; peripheral arterial disease; epidemiology; coronary artery disease ID ANKLE-BRACHIAL INDEX; LOWER-EXTREMITY; CARDIOVASCULAR-DISEASE; ALL-CAUSE; MORTALITY; ASSOCIATION; ANGIOGRAPHY; PERFORMANCE; GUIDELINES; ADULTS AB Background: Peripheral arterial disease (PAD) is under diagnosed in primary care practices, yet the extent of unrecognized PAD in patients with coronary artery disease (CAD) is unknown. Objective: To assess the prevalence of previously unrecognized PAD in patients undergoing coronary angiography and/or intervention and to determine the relationship between presence of PAD and severity of CAD. Methods: The Peripheral Arterial Disease in Interventional Patients Study (PIPS) is a prospective cohort study conducted at an inpatient service of a tertiary referral center. A total of 800 patients referred for coronary angiography without prior diagnosis of PAD aged 70 years or older or aged 50-69 years with a history of tobacco use and/or diabetes mellitus were included. Evaluation involved a medical history, a questionnaire to assess symptoms and functional status, and measurement of the ankle-brachial index (ABI). PAD was considered present if the ABI was 0.90 or less. Results: The prevalence of previously unrecognized PAD was 15%, 95% CI (12.6-17.7) and was highest among patients over 70 years of age (25.2%) and in women (23.3%). Among patients with CAD, those with PAD had higher prevalence of left main and multivessel coronary artery disease (87.2% vs. 75.5%, P = 0.006). Alternatively, patients with multivessel CAD had a twofold higher risk of being diagnosed with previously unrecognized PAD compared with those with single vessel CAD [adjusted OR = 2.02, (95% CI 1.03-3.98)]. Conclusions: PAD is often overlooked even in patients with known ischemic heart disease under specialist cardiovascular care. Overlooked PAD in this population increases in frequency with advanced age, in women, and in the presence of other traditional cardiovascular risk factors. Furthermore, the presence of PAD in this population identifies a subgroup with more severe form of CAD. (C) 2009 Wiley-Liss, Inc. C1 [Moussa, Issam D.] Cornell Univ, Weill Med Coll, Div Cardiol, Weill Cornell Med Ctr,New York Presbyterian Hosp, New York, NY 10021 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mehran, Roxana; Gray, William; Dangas, George; Moses, Jeffery W.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [Lazic, Zoran] Lenox Hill Hosp, New York, NY 10021 USA. RP Moussa, ID (reprint author), Cornell Univ, Weill Med Coll, Div Cardiol, Weill Cornell Med Ctr,New York Presbyterian Hosp, 520 E 70th St,Starr Pavil 4,Box 08, New York, NY 10021 USA. EM ism9003@med.cornell.edu NR 21 TC 38 Z9 39 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD MAY 1 PY 2009 VL 73 IS 6 BP 719 EP 724 DI 10.1002/ccd.21969 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 439YJ UT WOS:000265663500001 PM 19213068 ER PT J AU Garcia, JA Agostoni, P Green, NE Maddux, JT Chen, SYJ Messenger, JC Casserly, IP Hansgen, A Wink, O Movassaghi, B Groves, BM Van Den Heuvel, P Verheye, S Van Langenhove, G Vermeersch, P Van den Branden, F Yeghiazarians, Y Michaels, AD Carroll, JD AF Garcia, Joel A. Agostoni, Pierfrancesco Green, Nathan E. Maddux, James T. Chen, S. -Y. James Messenger, John C. Casserly, Ivan P. Hansgen, Adam Wink, Onno Movassaghi, Babak Groves, Bertron M. Van Den Heuvel, Paul Verheye, Stefan Van Langenhove, Glenn Vermeersch, Paul Van den Branden, Frank Yeghiazarians, Yerem Michaels, Andrew D. Carroll, John D. TI Rotational vs. Standard Coronary Angiography: An Image Content Analysis SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE angiography coronary; diagnostic cardiac catheterization; contrast media; percutaneous coronary intervention; quantitative coronary angiography ID INTRAVASCULAR ULTRASOUND; ARTERY-DISEASE; CLINICAL UTILITY; ANGIOPLASTY; SAFETY AB Objective: To evaluate the clinical utility of images acquired from rotational coronary angiographic (RA) acquisitions compared to standard 'fixed' coronary angiography (SA). Background: RA is a novel angiographic modality that has been enabled by new gantry systems that allow calibrated automatic angiographic rotations and has been shown to reduce radiation and contrast exposure compared to SA. RA provides a dynamic multiple-angle perspective of the coronaries during a single contrast injection. Methods: The screening adequacy, lesion assessment, and a quantitative coronary analysis (QCA) of both SA and RA were compared by independent blinded review in 100 patients with coronary artery disease (CAD). Results: SA and RA recognize a similar total number of lesions (P = 0.61). The qualitative assessment of lesion characteristics and severity between modalities was comparable and lead to similar clinical decisions. Visualization of several vessel segments (diagonal, distal RCA, postero-lateral branches and posterior-descending) was superior with RA when compared to SA (P < 0.05). A QCA comparison (MLD, MLA, LL, % DS) revealed no difference between SA and RA. The volume of contrast (23.5 +/- 3.1 mL vs. 39.4 +/- 4.1; P = 0.0001), total radiation exposure (27.1 +/- 4 vs. 32.1 +/- 3.8 Gycm(2); p = 0.002) and image acquisition time (54.3 +/- 36.8 vs. 77.67 +/- 49.64 sec; P = 0.003) all favored RA. Conclusion: Coronary lesion assessment, coronary screening adequacy, and QCA evaluations are comparable in SA and RA acquisition modalities in the diagnosis of CAD however RA decreases contrast volume, image acquisition time, and radiation exposure. (C) 2009 Wiley-Liss, Inc. C1 [Garcia, Joel A.; Green, Nathan E.; Maddux, James T.; Chen, S. -Y. James; Messenger, John C.; Casserly, Ivan P.; Hansgen, Adam; Groves, Bertron M.; Carroll, John D.] Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver, CO 80262 USA. [Garcia, Joel A.] Denver Hlth Med Ctr, Div Cardiol, Denver, CO USA. [Agostoni, Pierfrancesco; Van Den Heuvel, Paul; Verheye, Stefan; Van Langenhove, Glenn; Vermeersch, Paul; Van den Branden, Frank] Antwerp Cardiovasc Inst Middelheim, Antwerp, Belgium. [Casserly, Ivan P.] Denver VA Med Ctr, Div Cardiol, Denver, CO USA. [Wink, Onno; Movassaghi, Babak] Philips Med Syst, Clin Res, Best, Netherlands. [Yeghiazarians, Yerem] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. [Michaels, Andrew D.] Univ Utah, Div Cardiol, Salt Lake City, UT 84112 USA. RP Carroll, JD (reprint author), Univ Colorado, Hlth Sci Ctr, Div Cardiol, 4200 E 9th Ave,Box B-132, Denver, CO 80262 USA. EM john.carroll@uchsc.edu NR 20 TC 19 Z9 23 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD MAY 1 PY 2009 VL 73 IS 6 BP 753 EP 761 DI 10.1002/ccd.21918 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 439YJ UT WOS:000265663500008 PM 19180661 ER PT J AU Schmidt, EV Ravitz, MJ Chen, L Lynch, M AF Schmidt, Emmett V. Ravitz, Michael J. Chen, Li Lynch, Mary TI Growth controls connect Interactions between c-myc and the tuberous sclerosis complex-mTOR pathway SO CELL CYCLE LA English DT Review DE c-Myc; translation initiation regulation; rapamycin; tuberin ID ATYPICAL ADENOMATOUS HYPERPLASIA; RIBOSOME ENTRY SEGMENT; CANCER-CELL METABOLISM; NORMAL RAT-TISSUES; RNA-POLYMERASE-I; CYCLIN D1; TRANSLATION INITIATION; TSC2 GENE; EKER RAT; PULMONARY LYMPHANGIOLEIOMYOMATOSIS AB Among other signals, cell growth is particularly controlled by the target of rapamycin (TOR) pathway that includes the tuberous sclerosis complex genes (TSC1/2), and through transcriptional effects regulated by c-myc. Overexpression of Drosophila Myc and TSC1/2 cause opposing growth and proliferation defects. Despite this relationship, direct regulatory connections between Myc and the TSC have only recently been evaluated. Other than studies of p53 regulation, little consideration has been given to transcriptional regulation of the TSC genes. Here we review evidence that transcriptional controls are potentially important regulators of TSC2 expression, and that Myc is a direct repressor of its expression. Since tuberin loss de-represses Myc protein, the connection between these two growth regulators is positioned to act as a feed-forward loop that would amplify the oncogenic effects of decreased tuberin or increased Myc. Further experiments will be needed to clarify the mechanisms underlying this important connection, and evaluate its overall contribution to cancers caused by TSC loss or Myc gain. C1 [Schmidt, Emmett V.] Massachusetts Gen Hosp, Canc Res Ctr, MGH Pediat, Lab Tumor Biol, Boston, MA 02114 USA. [Schmidt, Emmett V.; Ravitz, Michael J.; Chen, Li; Lynch, Mary] Harvard Univ, Sch Med, Boston, MA USA. [Schmidt, Emmett V.] Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children, Boston, MA 02115 USA. RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Canc Res Ctr, MGH Pediat, Lab Tumor Biol, 55 Fruit St GRJ 904, Boston, MA 02114 USA. EM Schmidt@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA063117-10, R01 CA069069-10] NR 111 TC 22 Z9 22 U1 2 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY 1 PY 2009 VL 8 IS 9 BP 1344 EP 1351 DI 10.4161/cc.8.9.8215 PG 8 WC Cell Biology SC Cell Biology GA 446IF UT WOS:000266114600019 PM 19342893 ER PT J AU Yanike, M Wirth, S Smith, AC Brown, EN Suzuki, WA AF Yanike, Marianna Wirth, Sylvia Smith, Anne C. Brown, Emery N. Suzuki, Wendy A. TI Comparison of Associative Learning-Related Signals in the Macaque Perirhinal Cortex and Hippocampus SO CEREBRAL CORTEX LA English DT Article DE changing cells; conditional-motor associations; electrophysiology; medial temporal lobe; primates; stimulus-response learning ID INFERIOR TEMPORAL CORTEX; CONDITIONAL OCULOMOTOR ASSOCIATIONS; COMPLEX NATURALISTIC SCENES; SUPPLEMENTARY EYE FIELD; LONG-TERM-MEMORY; RECOGNITION MEMORY; NEURONAL-ACTIVITY; ENTORHINAL CORTEX; RHINAL CORTEX; INFEROTEMPORAL NEURONS AB Strong evidence suggests that the macaque monkey perirhinal cortex is involved in both the initial formation as well as the long-term storage of associative memory. To examine the neurophysiological basis of associative memory formation in this area, we recorded neural activity in this region as monkeys learned new conditional-motor associations. We report that a population of perirhinal neurons signal newly learned associations by changing their firing rate correlated with the animal's behavioral learning curve. Individual perirhinal neurons signal learning of one or more associations concurrently and these neural changes could occur before, at the same time, or after behavioral learning was expressed. We also compared the associative learning signals in the perirhinal cortex to our previous findings in the hippocampus. We report global similarities in both the learning-related and task-related activity seen across these areas as well as clear differences in the within and across trial timing and relative proportion of different subtypes of learning-related signals. Taken together, these findings emphasize the important role of the perirhinal cortex in new associative learning and suggest that the perirhinal cortex together with the hippocampus contribute importantly to conditional-motor associative memory formation. C1 [Yanike, Marianna; Suzuki, Wendy A.] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Wirth, Sylvia] Ctr Natl Rech Sci, Ctr Neurosci Cognit, F-69675 Bron, France. [Smith, Anne C.] Univ Calif Davis, Dept Anesthesiol & Pain Med, Davis, CA 95616 USA. [Brown, Emery N.] Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Suzuki, WA (reprint author), NYU, Ctr Neural Sci, 4 Washington Pl Room 809, New York, NY 10003 USA. EM wendy@cns.nyu.edu FU National Institutes of Health [MH58847, DA015644]; McKnight foundation [R01 MH071847] FX National Institutes of Health grant (MH58847) to W. A. S.; a McKnight foundation grant to W. A. S.; R01 MH071847 to E. N. B. and National Institutes of Health grant (DA015644) to E. N. B. and W. A. S. NR 64 TC 24 Z9 24 U1 0 U2 6 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 MAY PY 2009 VL 19 IS 5 BP 1064 EP 1078 DI 10.1093/cercor/bhn156 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 431WM UT WOS:000265095500007 PM 18936274 ER PT J AU Nishida, M Pearsall, J Buckner, RL Walker, MP AF Nishida, Masaki Pearsall, Jori Buckner, Randy L. Walker, Matthew P. TI REM Sleep, Prefrontal Theta, and the Consolidation of Human Emotional Memory SO CEREBRAL CORTEX LA English DT Article DE consolidation; emotion; memory; REM; prefrontal; theta ID MEDIAL TEMPORAL-LOBE; POSTTRAUMATIC-STRESS-DISORDER; EYE-MOVEMENT SLEEP; PARADOXICAL SLEEP; ACETYLCHOLINE-RELEASE; PROLONGED INCREASES; DECLARATIVE MEMORY; FRONTAL-CORTEX; AVOIDANCE-TASK; AMYGDALA AB Both emotion and sleep are independently known to modulate declarative memory. Memory can be facilitated by emotion, leading to enhanced consolidation across increasing time delays. Sleep also facilitates offline memory processing, resulting in superior recall the next day. Here we explore whether rapid eye movement (REM) sleep, and aspects of its unique neurophysiology, underlie these convergent influences on memory. Using a nap paradigm, we measured the consolidation of neutral and negative emotional memories, and the association with REM-sleep electrophysiology. Subjects that napped showed a consolidation benefit for emotional but not neutral memories. The No-Nap control group showed no evidence of a consolidation benefit for either memory type. Within the Nap group, the extent of emotional memory facilitation was significantly correlated with the amount of REM sleep and also with right-dominant prefrontal theta power during REM. Together, these data support the role of REM-sleep neurobiology in the consolidation of emotional human memories, findings that have direct translational implications for affective psychiatric and mood disorders. C1 [Nishida, Masaki; Pearsall, Jori; Walker, Matthew P.] Univ Calif Berkeley, Dept Psychol, Sleep & Neuroimaging Lab, Berkeley, CA 94702 USA. [Nishida, Masaki; Pearsall, Jori; Walker, Matthew P.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94702 USA. [Nishida, Masaki] Tokyo Med & Dent Univ, Grad Sch, Sect Psychiat & Behav Sci, Bunkyo Ku, Tokyo, Japan. [Pearsall, Jori; Buckner, Randy L.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Howard Hughes Med Inst, Davis, CA 95618 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Anthinoula A Martinos Ctr, Boston, MA 02114 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Anthinoula A Martinos Ctr, Boston, MA 02114 USA. RP Walker, MP (reprint author), Univ Calif Berkeley, Dept Psychol, Tolman Hall 3331, Berkeley, CA 94720 USA. EM mpwalker@berkeley.edu FU National Institutes of Health [MH069935]; Howard Hughes Medical Institute; American Academy of Sleep Medicine; Berkeley Research Impact Initiative FX National Institutes of Health (MH069935); the Howard Hughes Medical Institute; and the American Academy of Sleep Medicine. Funding to pay the Open Access publication charges for this article were provided by The Berkeley Research Impact Initiative. NR 64 TC 157 Z9 161 U1 9 U2 47 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 MAY PY 2009 VL 19 IS 5 BP 1158 EP 1166 DI 10.1093/cercor/bhn155 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 431WM UT WOS:000265095500015 PM 18832332 ER PT J AU Haspel, J Bauer, K Goehler, A Roberts, DH AF Haspel, Jeffrey Bauer, Kenneth Goehler, Alexander Roberts, David H. TI Long-term Anticoagulant Therapy for Idiopathic Pulmonary Embolism in the Elderly A Decision Analysis SO CHEST LA English DT Article DE anticoagulation; decision analysis; elderly; pulmonary embolism; warfarin ID RECURRENT VENOUS THROMBOEMBOLISM; DEEP-VEIN THROMBOSIS; ATRIAL-FIBRILLATION; POSTTHROMBOTIC SYNDROME; ORAL ANTICOAGULATION; MAJOR HEMORRHAGE; RISK-FACTORS; WARFARIN; PREVENTION; DISEASE AB Background: Elderly patients with idiopathic pulmonary embolism (PE) are at high risk for recurrent venous thromboembolic disease and might benefit from long-term anticoagulant therapy. But they are also at higher risk for bleeding complications. Because there have been no clinical trials addressing PE treatment in elderly patients, the balance of therapeutic benefits and risks is unclear. Methods: We constructed a decision-analytic model to forecast the effects of long-term warfarin therapy, for idiopathic PE. We focused on 65- and 80-year-old outpatients, with or without a propensity for falls, who previously had completed 6 to 12 months of anticoagulant therapy without experiencing a major bleed. The model incorporated age-appropriate thromboembolic recurrence rates after PE, major bleeding risks of warfarin use, and the contribution of falls to major bleeding episodes in anticoagulated elderly, patients. We used probabilistic sensitivity analysis to model outcomes over ranges of potential thromboembolic and bleeding risks. Results: In our baseline analysis, long-term warfarin was superior to conventional duration therapy,. Depending on the patient subgroup (stratified by age and fall risk), it increased life expectancy, by 0.16 to 0.56 years and event-free life expectancy by 0.32 to 0.51 years. Probabilistic sensitivity analysis demonstrated that long-term warfarin therapy was likely to increase life expectancy when compared with conventional-duration therapy (76 to 93% likelihood across all groups). Conclusions; Extended anticoagulant therapy for idiopathic PE may be beneficial in a subgroup of elderly patients who tolerate the initial 6 to 12 months of therapy without bleeding complications. In this population, advanced age and fall risk were not contraindications to long-term anticoagulation. (CHEST 2009; 135:1243-1251) C1 [Haspel, Jeffrey; Roberts, David H.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA. [Bauer, Kenneth] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol, Boston, MA 02215 USA. [Goehler, Alexander] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Roberts, DH (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, 330 Brookline Ave,KSB-23, Boston, MA 02215 USA. EM dhrobert@bidmc.harvard.edu NR 42 TC 4 Z9 6 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2009 VL 135 IS 5 BP 1243 EP 1251 DI 10.1378/chest.08-1164 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 442YF UT WOS:000265876100020 PM 19017863 ER PT J AU Sosnovik, DE Wang, RP Dai, GP Wang, T Aikawa, E Novikov, M Rosenzweig, A Gilbert, RJ Wedeen, VJ AF Sosnovik, David E. Wang, Ruopeng Dai, Guangping Wang, Teresa Aikawa, Elena Novikov, Mikhael Rosenzweig, Anthony Gilbert, Richard J. Wedeen, Van J. TI Diffusion Spectrum MRI Tractography Reveals the Presence of a Complex Network of Residual Myofibers in Infarcted Myocardium SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE myocardial infarction; fiber architecture; MRI; diffusion; myocardium ID MAGNETIC-RESONANCE; TENSOR MRI; HYPERTROPHIC CARDIOMYOPATHY; FIBER-ORIENTATION; CARDIAC FIBER; BOVINE TONGUE; IN-VIVO; ARCHITECTURE; HEART; MOTION AB Background-Changes in myocardial microstructure are important components of the tissue response to infarction but are difficult to resolve with current imaging techniques. A novel technique, diffusion spectrum MRI tractography (DSI tractography), was thus used to image myofiber architecture in normal and infarcted myocardium. Unlike diffusion tensor imaging, DSI tractography resolves multiple myofiber populations per voxel, thus generating accurate 3D tractograms, which we present in the myocardium for the first time. Methods and Results-DSI tractography was performed at 4.7 T in excised rat hearts 3 weeks after left coronary artery ligation (n=4) and in 4 age-matched controls. Fiber architecture in the control hearts varied smoothly from endocardium to epicardium, producing a symmetrical array of crossing helical structures in which orthogonal myofibers were separated by fibers with intermediate helix angles. Fiber architecture in the infarcted hearts was severely perturbed. The infarct boundary in all cases was highly irregular and punctuated repeatedly by residual myofibers extending from within the infarct to the border zones. In all infarcts, longitudinal myofibers extending toward the basal-anterior wall and transversely oriented myofibers extending toward the septum lay in direct contact with each other, forming nodes of orthogonal myofiber intersection or contact. Conclusions-DSI tractography resolves 3D myofiber architecture and reveals a complex network of orthogonal myofibers within infarcted myocardium. Meshlike networks of orthogonal myofibers in infarcted myocardium may resist mechanical remodeling but also probably increase the risk for lethal reentrant arrhythmias. DSI tractography thus provides a new and important readout of tissue injury after myocardial infarction. (Circ Cardiovasc Imaging. 2009;2: 206-212.) C1 [Sosnovik, David E.; Wang, Ruopeng; Dai, Guangping; Wedeen, Van J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging,Dept Radiol, Boston, MA USA. [Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Sosnovik, David E.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Wang, Teresa; Gilbert, Richard J.] MIT, Dept Mech & Biol Engn, Cambridge, MA 02139 USA. [Aikawa, Elena; Rosenzweig, Anthony] Harvard Univ, Sch Med, Leducq Fdn Network, Boston, MA USA. [Novikov, Mikhael; Rosenzweig, Anthony] Harvard Univ, Sch Med, Beth Israel Med Ctr, Cardiovasc Inst, Boston, MA USA. RP Sosnovik, DE (reprint author), 149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu FU National Institutes of Health [R01 HL093038, K08 HL079984]; NCRR [P41RR14075]; [RO1 DC05604]; [RO1 MH64044] FX This study was supported in part by the following grants from the National Institutes of Health: R01 HL093038 and K08 HL079984 (to D.E. S.), RO1 DC05604 (to R.J.G.), RO1 MH64044 (to V.J.W.), and NCRR P41RR14075 (to the Martinos Center for Biomedical Imaging), as well as by the Leducq Foundation (to E.A. and A.R.). NR 29 TC 54 Z9 58 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2009 VL 2 IS 3 BP 206 EP 212 DI 10.1161/CIRCIMAGING.108.815050 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 450RB UT WOS:000266417400009 PM 19808594 ER PT J AU Hoffmann, U Bamberg, F AF Hoffmann, Udo Bamberg, Fabian TI CT Coronary Angiography Is the Most Accurate and Effective Noninvasive Imaging Tool for Evaluating Patients Presenting With Chest Pain to the Emergency Department SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Editorial Material ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; LEFT-VENTRICULAR FUNCTION; ACUTE CARDIAC ISCHEMIA; LOW-RISK PATIENTS; ARTERY-DISEASE; UNSTABLE ANGINA; MAGNETIC-RESONANCE; DIAGNOSTIC-ACCURACY C1 [Hoffmann, Udo; Bamberg, Fabian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Dept Radiol, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org NR 113 TC 13 Z9 13 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2009 VL 2 IS 3 BP 251 EP 263 DI 10.1161/CIRCIMAGING.109.850347 PG 13 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 450RB UT WOS:000266417400015 PM 19808600 ER PT J AU Sullivan, MD Ciechanowski, PS Russo, JE Soine, LA Jordan-Keith, K Ting, HH Caldwell, JH AF Sullivan, Mark D. Ciechanowski, Paul S. Russo, Joan E. Soine, Laurie A. Jordan-Keith, Kier Ting, Henry H. Caldwell, James H. TI Understanding Why Patients Delay Seeking Care for Acute Coronary Syndromes SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE prehospital delay; attachment theory; depression; anxiety; trust ID ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; HEART-ATTACK SYMPTOMS; RAPID EARLY ACTION; HOSPITAL PRESENTATION; PREHOSPITAL DELAY; ARTERY-DISEASE; HEALTH-CARE; TIME; MORTALITY AB Background-Better insight into the psychosocial factors associated with prehospital delays in seeking care for acute coronary syndromes is needed to inform the design of future interventions. Delay in presenting for care after the onset of symptoms is common, limits the potential benefit of acute reperfusion, and has not been reduced by interventions tested thus far. Methods and Results-Seven hundred ninety-six patients with suspected ischemic heart disease scheduled for clinically indicated imaging stress tests completed questionnaires concerning psychological distress and attachment styles (worthiness to receive care, trustworthiness of others to provide care). The primary dependent variable for this study was response to a question from the rapid early action for coronary treatment trial concerning intention to "wait until very sure" before seeking care for a possible "heart attack." Responses to this question were strongly associated with actual emergency department-reported and self-reported care delay in the rapid early action for coronary treatment trial. In multivariable ordinal regression models, a more negative view of the trustworthiness of others, greater physical limitations from angina, and no previous revascularization were independently associated with increased intention to wait to seek care for a myocardial infarction. Intention to wait was not associated with inducible ischemia or self-perceived risk of myocardial infarction. Conclusions-Intention to delay seeking care for acute coronary syndromes is associated with a patient's view of the trustworthiness of others, previous experience with revascularization, and functional limitations, even after adjustment for objective and perceived acute coronary syndromes risk. These findings provide insight into novel factors contributing to longer delay times and may inform future interventions to reduce delay time. (Circ Cardiovasc Qual Outcomes. 2009; 2: 148-154.) C1 [Sullivan, Mark D.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Soine, Laurie A.; Caldwell, James H.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Soine, Laurie A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Soine, Laurie A.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Jordan-Keith, Kier] VA Puget Sound Hlth Care Syst, Dept Cardiol, Seattle, WA USA. [Ting, Henry H.] Mayo Clin, Knowledge & Encounter Res Unit, Div Cardiovasc Dis, Rochester, MN USA. RP Sullivan, MD (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Box 356560,1959 NE Pacific St, Seattle, WA 98195 USA. EM sullimar@u.washington.edu FU American Heart Association [0450094Z] FX This work was supported by a grant from the American Heart Association (0450094Z to M. S.). NR 33 TC 26 Z9 27 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2009 VL 2 IS 3 BP 148 EP 154 DI 10.1161/CIRCOUTCOMES.108.825471 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575NN UT WOS:000276074000004 PM 20031831 ER PT J AU Popescu, I Werner, RM Vaughan-Sarrazin, MS Cram, P AF Popescu, Ioana Werner, Rachel M. Vaughan-Sarrazin, Mary S. Cram, Peter TI Characteristics and Outcomes of America's Lowest-Performing Hospitals An Analysis of Acute Myocardial Infarction Hospital Care in the United States SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE myocadial infarction; hospitals; quality of health care ID QUALITY-OF-CARE; SAFETY-NET HOSPITALS; MORTALITY-RATES; US HOSPITALS; FOR-PROFIT; MEDICARE; IMPROVEMENT; DIFFERENCE; OWNERSHIP; SURGERY AB Background-Studies suggest that most hospitals now have relatively high adherence with recommended acute myocardial infarction (AMI) process measures. Little is known about hospitals with consistently poor adherence with AMI process measures and whether these hospitals also have increased patient mortality. Methods and Results-We conducted a retrospective study of 2761 US hospitals reporting AMI process measures to the Center for Medicare and Medicaid Services Hospital Compare database during 2004 to 2006 that could be linked to 2005 Medicare Part A data. The main outcome measures were hospitals' combined compliance with 5 AMI measures (aspirin and beta-blocker on admission and discharge and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use at discharge for patients with left ventricular dysfunction) and risk-adjusted 30-day mortality for 2005. We stratified hospitals into those with low AMI adherence (ranked in the lowest decile for AMI adherence for 3 consecutive years [2004-2006, n=105]), high adherence (ranked in the top decile for 3 consecutive years [n=63]), and intermediate adherence (all others [n=2593]). Mean AMI performance varied significantly across low-, intermediate-, and high-performing hospitals (mean score, 68% versus 92% versus 99%, P<0.001). Low-performing hospitals were more likely than intermediate-and high-performing hospitals to be safety-net providers (19.2% versus 11.0% versus 6.4%; P=0.005). Low-performing hospitals had higher unadjusted 30-day mortality rates (23.6% versus 17.8% versus 14.9%; P<0.001). These differences persisted after adjustment for patient characteristics (16.3% versus 16.0% versus 15.7%; P=0.02). Conclusion-Consistently low-performing hospitals differ substantially from other US hospitals. Targeting quality improvement efforts toward these hospitals may offer an attractive opportunity for improving AMI outcomes. (Circ Cardiovasc Qual Outcomes. 2009; 2: 221-227.) C1 [Popescu, Ioana; Vaughan-Sarrazin, Mary S.; Cram, Peter] Iowa City VA Med Ctr, Ctr Res Implementat Innovat Strategies Practice, Iowa City, IA USA. [Popescu, Ioana; Vaughan-Sarrazin, Mary S.; Cram, Peter] Univ Iowa, Carver Coll Med, Dept Internal Med, Div Gen Internal Med, Iowa City, IA 52240 USA. [Werner, Rachel M.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Werner, Rachel M.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Popescu, I (reprint author), Univ Iowa, Hosp & Clin, Dept Internal Med, 200 Hawkins Dr,SE615 GH, Iowa City, IA 52240 USA. EM Ioana-popescu@uiowa.edu RI Cram, Peter/K-4472-2014; OI Cram, Peter/0000-0002-1910-346X; Vaughan Sarrazin, Mary/0000-0001-8717-1061 FU Health Services Research and Development Service, Veterans Health Administration, Department of Veterans Affairs [HFP 04-149]; Ruth L. Kirschstein National Research Service Award; American Heart Association; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service; Agency for Healthcare Research and Quality [HS016478-01]; Department of Veterans Affairs, Health Services Research and Development Service; Williams Award; Department of Veterans Affairs, Health Services Research and Development [IIR 06-196-2]; National Center for Research Resources at the NIH [RR01997201]; Robert Wood Johnson Physician Faculty Scholars Program; National Heart Lung and Blood Institute at the NIH [R01 HL085347-01A1] FX For data acquisition, management, and analysis, this research was supported, in part, by an award (HFP 04-149) from the Health Services Research and Development Service, Veterans Health Administration, Department of Veterans Affairs. Dr Popescu is supported by a Ruth L. Kirschstein National Research Service Award, and by a National Scientist Development award from the American Heart Association. Dr Vaughan-Sarrazin is a Research Scientist in the Center for Research in the Implementation of Innovative Strategies in Practice (CRIISP) at the Iowa City VA Medical Center, which is funded through the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service. Dr Werner is supported by R01 HS016478-01 from the Agency for Healthcare Research and Quality, by a Career Development Award from the Department of Veterans Affairs, Health Services Research and Development Service, by a T. Franklin Williams Award in Geriatrics, and by a Merit Award (IIR 06-196-2) from the Department of Veterans Affairs, Health Services Research and Development. Dr Cram is supported by a K23 career development award (RR01997201) from the National Center for Research Resources at the NIH, by the Robert Wood Johnson Physician Faculty Scholars Program, and by R01 HL085347-01A1 from National Heart Lung and Blood Institute at the NIH. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 32 TC 18 Z9 18 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2009 VL 2 IS 3 BP 221 EP 227 DI 10.1161/CIRCOUTCOMES.108.813790 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575NN UT WOS:000276074000014 PM 20031841 ER PT J AU Pavlik, VN Greisinger, AJ Pool, J Haidet, P Hyman, DJ AF Pavlik, Valory N. Greisinger, Anthony J. Pool, James Haidet, Paul Hyman, David J. TI Does Reducing Physician Uncertainty Improve Hypertension Control? Rationale and Methods SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE hypertension; blacks; randomized controlled trial; blood pressure monitoring, ambulatory ID AMBULATORY BLOOD-PRESSURE; UNITED-STATES; UNCONTROLLED HYPERTENSION; ANTIHYPERTENSIVE THERAPY; PRIMARY-CARE; PREVALENCE; ADHERENCE; AWARENESS; TRENDS; POPULATION AB Hypertension affects nearly one third of the US population overall, and the prevalence rises sharply with age. In spite of public educational campaigns and professional education programs to encourage blood pressure measurement and control of both systolic and diastolic control to <140/90 mm Hg (or 130/80 mm Hg if diabetic), 43% of treated hypertensives do not achieve the recommended Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure target. Among blacks, 48% are uncontrolled on treatment. The majority of persons classified as poorly controlled hypertensives have mild systolic blood pressure elevation (in the range of 140 to 160 mm Hg). We hypothesized that physician uncertainty regarding the patient's usual blood pressure, as well as uncertainty regarding the extent of medication nonadherence, represent an important barrier to further reductions in the proportion of uncontrolled hypertensives in the United States. Using cluster randomization, 10 primary care clinics (6 from a public health care system and 4 from a private clinic system) were randomized to either the uncertainty reduction intervention condition or to usual care. An average of 68 patients per clinic were recruited to serve as units of observation. Physicians in the 5 intervention clinics were provided with a specially designed study form that included a graph of recent blood pressure measurements in their study patients, a check box to indicate their assessment of the adequacy of the patient's blood pressure control, and a menu of services they could order to aid in patient management. These menu options included 24-hour ambulatory blood pressure monitoring; electronic bottle cap assessment of medication adherence, followed by medication adherence counseling in patients found to be nonadherent; and lifestyle assessment and counseling followed by 24-hour ambulatory blood pressure monitoring. Physicians in the 5 usual practice clinics did not have access to these services but were informed of which patients had been enrolled in the study. Substudies carried out to further characterize the study population and interpret intervention results included ambulatory blood pressure monitoring and electronic bottle cap monitoring in a random subsample of patients at baseline, and audio recording of patient-physician encounters after intervention implementation. The primary study end point was defined as the proportion of patients with controlled blood pressure (<140/90 mm Hg or <130/80 mm Hg if diabetic). Secondary end points include actual measured clinic systolic and diastolic blood pressure, patient physician communication patterns, physician prescribing patient self-reported lifestyle and medication adherence, physician knowledge, attitude and beliefs regarding the utility of intervention tools to achieve blood pressure control, and the cost-effectiveness of the intervention. Six-hundred eighty patients have been randomized, and 675 remain in active follow-up after 1.5 years. Patient closeout will be complete in March 2009. Analyses of the baseline data are in progress. Office-based blood pressure measurement error and bias, as well as physician and patient beliefs about the need for treatment intensification, may be important factors that limit further progress in blood pressure control. This trial will provide data on the extent to which available technologies not widely used in primary care will change physician prescribing behavior and patient adherence to prescribed treatment. (Circ Cardiovasc Qual Oucomes. 2009; 2: 257-263.) C1 [Pavlik, Valory N.] Baylor Coll Med, Dept Family & Community Med, Houston, TX 77098 USA. [Greisinger, Anthony J.] Kelsey Res Fdn, Houston, TX USA. [Haidet, Paul] DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Pavlik, VN (reprint author), Baylor Coll Med, Dept Family & Community Med, 3701 Kirby Dr,Suite 600, Houston, TX 77098 USA. EM vpavlik@bcm.tmc.edu FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL078589] FX This study was supported by grant R01 HL078589 from the National Heart, Lung, and Blood Institute of the National Institutes of Health. NR 31 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2009 VL 2 IS 3 BP 257 EP 263 DI 10.1161/CIRCOUTCOMES.109.849984 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575NN UT WOS:000276074000019 PM 20031846 ER PT J AU Tsai, VW Cooper, J Garan, H Natale, A Ptaszek, LM Ellinor, PT Hickey, K Downey, R Zei, P Hsia, H Wang, P Hunt, S Haddad, F Al-Ahmad, A AF Tsai, Vivian W. Cooper, Joshua Garan, Hasan Natale, Andrea Ptaszek, Leon M. Ellinor, Patrick T. Hickey, Kathleen Downey, Ross Zei, Paul Hsia, Henry Wang, Paul Hunt, Sharon Haddad, Francois Al-Ahmad, Amin TI The Efficacy of Implantable Cardioverter-Defibrillators in Heart Transplant Recipients Results From a Multicenter Registry SO CIRCULATION-HEART FAILURE LA English DT Article DE sudden death; implantable cardioverter-defibrillator; orthotopic heart transplant ID ORTHOTOPIC CARDIAC TRANSPLANTATION; LONG-TERM SURVIVORS; VENTRICULAR-FIBRILLATION; SUDDEN; DEATH; ARRHYTHMIAS; ABNORMALITIES; PREVALENCE; AUTOPSY; DISEASE AB Background-Sudden cardiac death among orthotopic heart transplant recipients is an important mechanism of death after cardiac transplantation. The role for implantable cardioverter-defibrillators (ICDs) in this population is not well established. This study sought to determine whether ICDs are effective in preventing Sudden cardiac death in high-risk heart transplant recipients. Methods and Results-We retrospectively analyzed the records of all orthotopic heart transplant patients who had ICD implantation between January 1995 and December 2005 at 5 heart transplant centers. Thirty-six patients were considered high risk for sudden cardiac death. The mean age at orthotopic heart transplant was 44 +/- 14 years, the majority being male (n=29). The mean age at ICD implantation was 52 +/- 14 years, whereas the average time from orthotopic heart transplant to ICD implant was 8 years +/- 6 years. The main indications for ICD implantation were severe allograft vasculopathy (n=12), unexplained syncope (n=9), history of cardiac arrest (n=8), and severe left ventricular dysfunction (n=7). Twenty-two shocks were delivered to 10 patients (28%), of whom 8 (80%) received 12 appropriate shocks for either rapid ventricular tachycardia or ventricular fibrillation. The shocks were effective in terminating the ventricular arrhythmias in all cases. Three (8%) patients received 10 inappropriate shocks. Underlying allograft vasculopathy was present in 100% (8 of 8) of patients who received appropriate ICD therapy. Conclusions-Use of ICDs after heart transplantation may be appropriate in selected high-risk patients. Further studies are needed to establish an appropriate prevention strategy in this population. (Circ Heart Fail. 2009;2:197-201.) C1 [Tsai, Vivian W.; Zei, Paul; Hsia, Henry; Wang, Paul; Hunt, Sharon; Haddad, Francois; Al-Ahmad, Amin] Stanford Univ, Dept Cardiovasc Med, Stanford, CA 94305 USA. [Cooper, Joshua] Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. [Garan, Hasan; Hickey, Kathleen] Columbia Univ, Div Cardiol, New York, NY 10027 USA. [Ptaszek, Leon M.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Arrhythmia Serv, Boston, MA 02114 USA. [Downey, Ross] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Natale, Andrea] St Davids Med Ctr, Austin, TX USA. RP Tsai, VW (reprint author), CVRC, 300 Pasteur Dr, Stanford, CA 94305 USA. EM vtsai@stanfordalumni.org NR 31 TC 20 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2009 VL 2 IS 3 BP 197 EP 201 DI 10.1161/CIRCHEARTFAILURE.108.814525 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 485YF UT WOS:000269161600007 PM 19808340 ER PT J AU Dixon, JA Spinale, FG AF Dixon, Jennifer A. Spinale, Francis G. TI Large Animal Models of Heart Failure A Critical Link in the Translation of Basic Science to Clinical Practice SO CIRCULATION-HEART FAILURE LA English DT Article DE myocardial infarction; myocardial remodeling; overload states; rapid pacing ID MESENCHYMAL STEM-CELLS; LEFT-VENTRICULAR FUNCTION; ACUTE MYOCARDIAL-INFARCTION; MATRIX-METALLOPROTEINASE INHIBITION; CHRONIC MITRAL REGURGITATION; VOLUME OVERLOAD HYPERTROPHY; CARDIAC SUPPORT DEVICE; BONE-MARROW-CELLS; DILATED CARDIOMYOPATHY; RECEPTOR BLOCKADE AB Congestive heart failure (HF) is a clinical syndrome, with hallmarks of fatigue and dyspnea, that continues to be highly prevalent and morbid. Because of the growing burden of HF as the population ages, the need to develop new pharmacological treatments and therapeutic interventions is of paramount importance. Common pathophysiologic features of HF include changes in left ventricle structure, function, and neurohormonal activation. The recapitulation of the HF phenotype in large animal models can allow for the translation of basic science discoveries into clinical therapies. Models of myocardial infarction/ischemia, ischemic cardiomyopathy, ventricular pressure and volume overload, and pacing-induced dilated cardiomyopathy have been created in dogs, pigs, and sheep for the investigation of HF and potential therapies. Large animal models recapitulating the clinical HF phenotype and translating basic science to clinical applications have successfully traveled the journey from bench to bedside. Undoubtedly, large animal models of HF will continue to play a crucial role in the elucidation of biological pathways involved in HF and the development and refinement of HF therapies. (Circ Heart Fail. 2009;2:262-271.) C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Strom Thurmond Res Ctr, 114 Doughty St,Suite 625, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU NHLBI NIH HHS [P01 HL048788, P01 HL048788-150006] NR 79 TC 115 Z9 115 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2009 VL 2 IS 3 BP 262 EP 271 DI 10.1161/CIRCHEARTFAILURE.108.814459 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 485YF UT WOS:000269161600015 PM 19808348 ER PT J AU Figueiredo, JL Nahrendorf, M Sosnovik, DE Weissleder, R AF Figueiredo, Jose-Luiz Nahrendorf, Matthias Sosnovik, David E. Weissleder, Ralph TI MRI of a Novel Murine Working Heart Transplant Model SO CIRCULATION-HEART FAILURE LA English DT Editorial Material ID IRON-OXIDE PARTICLES; REJECTION C1 [Figueiredo, Jose-Luiz; Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Figueiredo, Jose-Luiz; Nahrendorf, Matthias; Sosnovik, David E.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. [Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Nahrendorf, M (reprint author), MGH CSB, CPZN-5206,185 Cambridge St, Boston, MA 02124 USA. EM mnahrendorf@mgh.harvard.edu FU NCI NIH HHS [R24-CA92782, R24 CA092782, R24 CA092782-05]; NHLBI NIH HHS [R01 HL095629, R01 HL096576] NR 5 TC 5 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2009 VL 2 IS 3 BP 272 EP U148 DI 10.1161/CIRCHEARTFAILURE.109.852707 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 485YF UT WOS:000269161600016 PM 19718275 ER PT J AU Olivova, P van der Veen, K Cullen, E Rose, M Zhang, XK Sims, KB Keutzer, J Browning, MF AF Olivova, Petra van der Veen, Kristen Cullen, Emmaline Rose, Michael Zhang, X. Kate Sims, Katherine B. Keutzer, Joan Browning, Marsha F. TI Effect of sample collection on alpha-galactosidase A enzyme activity measurements in dried blood spots on filter paper SO CLINICA CHIMICA ACTA LA English DT Article DE 4-MU fluorescent assay; alpha-galactosidase A; Dried blood spots on filter paper; Fabry disease ID LYSOSOMAL STORAGE DISORDERS; TANDEM MASS-SPECTROMETRY; FABRY-DISEASE; REPLACEMENT THERAPY; ASSAY; INVOLVEMENT; POPULATION; PREVALENCE; MANAGEMENT; DIAGNOSIS AB Background: Fabry disease is an X-linked lysosomal storage disorder due to deficiency of alpha galactosidase A (AGAL, EC 3.2.1.22). Despite increasing utilization of dried blood spot (DBS) as samples for AGAL enzyme assays, the effects of blood sample collection techniques on enzyme activity have not been studied. Methods: DBS samples were prepared by spotting blood collected into an ethylenediaminetetraacetic acid (EDTA) tube and by direct application of blood from a finger prick or a venipuncture syringe. AGAL activity was measured quantitatively by detecting the fluorescence of 4-methylumbelliferone (4-MU) generated using the substrate 4-methylumbelliferyl-alpha-D-glucopyranoside (4-MUGal) in an acidic pH for 20 h. N-acetyl-D-galactosamine (GalNAc) was used to inhibit alpha-galactosidase B (EC 3.2.1.49). Results: We studied 88 previously diagnosed Fabry disease patients and 690 healthy controls. Average AGAL activity in DBS samples prepared using EDTA tubes was higher compared to those spotted directly irrespective of disease status. Conclusions: The study confirms the need for collection method-specific reference ranges using DBS samples. (C) 2009 Elsevier B.V. All rights reserved. C1 [Olivova, Petra; Cullen, Emmaline; Rose, Michael; Zhang, X. Kate; Keutzer, Joan] Genzyme, Framingham, MA USA. [Browning, Marsha F.] Massachusetts Gen Hosp, CHGFL, MCH Neurogenet Lab Biochem, Simches Res Ctr,Lysosomal Disorders Unit, Boston, MA 02114 USA. [Sims, Katherine B.; Browning, Marsha F.] Harvard Univ, Sch Med, Boston, MA USA. [Sims, Katherine B.; Browning, Marsha F.] MGH Ctr Human Genet Res, Boston, MA USA. RP Browning, MF (reprint author), Massachusetts Gen Hosp, CHGFL, MCH Neurogenet Lab Biochem, Simches Res Ctr,Lysosomal Disorders Unit, 185 Cambridge St,Room 2222, Boston, MA 02114 USA. EM mfbrowning@partners.org FU Amicus Therapeutics; Fabry Support and Information Group (FSIG); MGH Louison/Callahan Research Fund (MFB) FX The authors thank the Fabry Support and Information Group (FSIG), and the Lysosomal Disease Network (LDN) for their participation, the Massachusetts General Hospital for Children nursing and phlebotomy staff for assistance; Virginia Clarke, RN, for clinical assistance; and the members of the MGH Neurogenetics Laboratory (Drs. Winnie Xin and Thomas Mullen, Rosemary Kiely, and Kellie Burke), and the families affected with Fabry disease for participation in this study. Funding was supported, in part, by a grant from Amicus Therapeutics, the Fabry Support and Information Group (FSIG) and the MGH Louison/Callahan Research Fund (MFB). We are grateful to the patients and physicians who contributed samples. NR 17 TC 18 Z9 19 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD MAY PY 2009 VL 403 IS 1-2 BP 159 EP 162 DI 10.1016/j.cca.2009.02.008 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 447KN UT WOS:000266190100030 PM 19245803 ER PT J AU Theodoulou, M Batist, G Campos, S Winer, E Welles, L Hudis, C AF Theodoulou, Maria Batist, Gerald Campos, Susana Winer, Eric Welles, Lauri Hudis, Clifford TI Phase I Study of Nonpegylated Liposomal Doxorubicin plus Trastuzumab in Patients with HER2-Positive Breast Cancer SO CLINICAL BREAST CANCER LA English DT Article DE Cardiac toxicity; Congestive heart failure; Left ventricular ejection fraction; Neutropenia ID CONVENTIONAL DOXORUBICIN; ENCAPSULATED DOXORUBICIN; MONOCLONAL-ANTIBODY; ANTITUMOR EFFICACY; MULTICENTER TRIAL; CARDIAC SAFETY; SINGLE-AGENT; CARDIOTOXICITY; CHEMOTHERAPY; EXPRESSION AB Background: This was an open-label, nonrandomized, multicenter, 2-stage phase I trial of safety and preliminary efficacy of nonpegylated liposomal doxorubicin (NLD) in combination with trastuzumab in advanced breast cancer, with emphasis on cardiac toxicity. Patients and Methods: Forty patients (median age, 48 years; range, 30-74 years) with HER2/neu 2+ or 3+ tumors (by immunohistochemistry) were recruited December 1999 to November 2002. Patients were eligible if they received <= 1 previous trastuzurnab regimen, <= 2 cytotoxic regimens for advanced breast cancer, and lifetime cumulative anthracycline doses <= 240 mg/m(2). The study regimen comprised NLD 60 mg/m(2) every 3 weeks and trastuzumab loading dose 4 mg/kg followed by 2 mg/kg weekly. Treatment cycles lasted 21 days. Clinical cardiac assessments were performed with multigated acquisition scans every 2 cycles. Patients were evaluated for cardiac toxicity after receiving >= 1 cycle. Cardiac safety was assessed after completing >= 4 full treatment cycles. Results: Thirty out of 40 patients (75%) received >= 4 treatment cycles and were evaluable for cardiac safety. Five patients (13%), 4 who were doxorubicin pretreated, developed left ventricular ejection fraction reductions to < 50%, and 2 (5%) of these patients experienced clinical cardiac toxicity Fifty percent of the patients had objective tumor responses; median progress ion-free survival was approximately 21 weeks. Twenty-six patients (65%) had grade 3/4 neutropenla; 2 patients experienced febrile neutropenia. Conclusion: Nonpegylated liposomal doxorubicin plus trastuzumab is active in HER2-positive patients with advanced breast cancer and is associated with a lower risk of cardiac toxicity than conventional doxorubicin plus trastuzumab. C1 [Theodoulou, Maria; Hudis, Clifford] Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, Div Solid Tumor Oncol, Dept Med, New York, NY 10021 USA. [Batist, Gerald] McGill Univ, Dept Oncol, Sir Mortimer B Davis Jewish Gen Hosp, Montreal, PQ, Canada. [Campos, Susana; Winer, Eric] Massachusetts Gen Hosp, Adult Oncol Dept, Dana Farber Canc Inst, Boston, MA 02114 USA. [Welles, Lauri] Cephalon, Maisons Alfort, France. RP Theodoulou, M (reprint author), Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, Div Solid Tumor Oncol, Dept Med, Box 315,1275 York Ave, New York, NY 10021 USA. EM theodoum@mskcc.org NR 27 TC 11 Z9 11 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD MAY PY 2009 VL 9 IS 2 BP 101 EP 107 DI 10.3816/CBC.2009.n.019 PG 7 WC Oncology SC Oncology GA 442KZ UT WOS:000265841400007 PM 19433391 ER PT J AU Yu, J Kane, S Wu, J Benedettini, E Li, DQ Reeves, C Innocenti, G Wetzel, R Crosby, K Becker, A Ferrante, M Cheung, WC Hong, XQ Chirieac, LR Sholl, LM Haack, H Smith, BL Polakiewicz, RD Tan, Y Gu, TL Loda, M Zhou, XM Comb, MJ AF Yu, Jian Kane, Susan Wu, Jiong Benedettini, Elisa Li, Daiqiang Reeves, Cynthia Innocenti, Gregory Wetzel, Randy Crosby, Katherine Becker, Alison Ferrante, Michelle Cheung, Wan Cheung Hong, Xiqiang Chirieac, Lucian R. Sholl, Lynette M. Haack, Herbert Smith, Bradley L. Polakiewicz, Roberto D. Tan, Yi Gu, Ting-Lei Loda, Massimo Zhou, Xinmin Comb, Michael J. TI Mutation-Specific Antibodies for the Detection of EGFR Mutations in Non-Small-Cell Lung Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID FACTOR-RECEPTOR GENE; KINASE DOMAIN MUTATIONS; PHASE-II; IMMUNOHISTOCHEMICAL EXPRESSION; GEFITINIB; CARCINOMA; THERAPY AB Purpose: Activating mutations within the tyrosine kinase domain of epidermal growth factor receptor (EGFR) are found in approximately 10% to 20% of non-small-cell lung cancer (NSCLC) patients and are associated with response to EGFR inhibitors. The most common NSCLC-associated EGFR mutations are deletions in exon 19 and L858R mutation in exon 21, together accounting for 90% of EGFR mutations. To develop a simple, sensitive, and reliable clinical assay for the identification of EGFR mutations in NSCLC patients, we generated mutation-specific rabbit monoclonal antibodies against each of these two most common EGFR mutations and aimed to evaluate the detection of EGFR mutations in NSCLC patients by immunohistochemistry. Experimental Design: We tested mutation-specific antibodies by Western blot, immunofluorescence, and immunohistochemistry. In addition, we stained 40 EGFR genotyped NSCLC tumor samples by immunohistochemistry with these antibodies. Finally, with a panel of four antibodies, we screened a large set of NSCLC patient samples with unknown genotype and confirmed the immunohistochemistry results by DNA sequencing. Results: These two antibodies specifically detect the corresponding mutant form of EGFR by Western blotting, immunofluorescence, and immunohistochemistry. Screening a panel of 340 paraffin-embedded NSCLC tumor samples with these antibodies showed that the sensitivity of the immunohistochemistry assay is 92%, with a specificity of 99% as compared with direct and mass spectrometry - based DNA sequencing. Conclusions: This simple assay for detection of EGFR mutations in diagnostic human tissues provides a rapid, sensitive, specific, and cost-effective method to identify lung cancer patients responsive to EGFR-based therapies. C1 [Yu, Jian; Kane, Susan; Wu, Jiong; Reeves, Cynthia; Innocenti, Gregory; Wetzel, Randy; Crosby, Katherine; Becker, Alison; Ferrante, Michelle; Hong, Xiqiang; Haack, Herbert; Smith, Bradley L.; Polakiewicz, Roberto D.; Tan, Yi; Gu, Ting-Lei; Comb, Michael J.] Cell Signaling Technol Inc, Danvers, MA 01923 USA. [Benedettini, Elisa; Chirieac, Lucian R.; Sholl, Lynette M.; Loda, Massimo] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. [Benedettini, Elisa; Chirieac, Lucian R.; Sholl, Lynette M.; Loda, Massimo] Brigham & Womens Hosp, Ctr Mol Oncol Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Li, Daiqiang] Cent S Univ, Xiangya Hosp 2, Dept Pathol, Changsha, Hunan, Peoples R China. [Zhou, Xinmin] Cent S Univ, Xiangya Hosp 2, Dept Cardiothorac Surg, Changsha, Hunan, Peoples R China. RP Comb, MJ (reprint author), Cell Signaling Technol Inc, 3 Trask Lane, Danvers, MA 01923 USA. EM xmzhou@xysm.net; mcomb@cellsignal.com FU National Cancer Institute Lung Specialized Program of Research Excellence [2P50 CA090578-06] FX Grant support: National Cancer Institute Lung Specialized Program of Research Excellence grant 2P50 CA090578-06 (M. Loda) and Ph.D. Program fellowship in Molecular Medicine, University of Milan, Italy (E. Benedettini). M. Loda is a Novartis Investigator. NR 16 TC 151 Z9 164 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2009 VL 15 IS 9 BP 3023 EP 3028 DI 10.1158/1078-0432.CCR-08-2739 PG 6 WC Oncology SC Oncology GA 440PL UT WOS:000265712100010 PM 19366827 ER PT J AU Cescon, DW Bradbury, PA Asomaning, K Hopkins, J Zhai, RH Zhou, W Wang, ZX Kulke, M Su, L Ma, C Xu, W Marshall, AL Heist, RS Wain, JC Lynch, TJ Christiani, DC Liu, G AF Cescon, David W. Bradbury, Penelope A. Asomaning, Kofi Hopkins, Jessica Zhai, Rihong Zhou, Wei Wang, Zhaoxi Kulke, Matthew Su, Li Ma, Clement Xu, Wei Marshall, Ariela L. Heist, Rebecca Suk Wain, John C. Lynch, Thomas J., Jr. Christiani, David C. Liu, Geoffrey TI p53 Arg72Pro and MDM2 T309G Polymorphisms, Histology, and Esophageal Cancer Prognosis SO CLINICAL CANCER RESEARCH LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISM; MDM2 PROMOTER POLYMORPHISM; BREAST-CANCER; LUNG-CANCER; CHEMOTHERAPY; ADENOCARCINOMA; CARCINOMA; ASSOCIATION; SURVIVAL; PATHWAY AB Purpose: This study aimed to evaluate the prognostic significance of two functional single nucleotide polymorphisms (SNP) in the p53 pathway (p53 Arg72Pro and MDM2 T309G) in patients with esophageal cancer, and to determine the importance of histologic subtype in the SNP-outcome relationships. Experimental Design: A cohort of 371 patients with esophageal carcinoma enrolled in Boston, USA from 1999 to 2004 were genotyped for the p53 and MDM2 SNPs. Associations between genotypes and overall survival (OS; the primary outcome) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. Cox proportional hazard models, adjusted for age, stage, performance status, and smoking were developed. Interaction analyses were done for histology (adenocarcinoma versus squamous cell carcinoma). Results: At the median follow-up of 33 months, median survival (MS) and PFS were 29.1 and 15.7 months, respectively. p53 Pro/Pro was strongly associated with shorter survival in the entire cohort (MS of 11.8 versus 29.1 months, P < 0.0001; adjusted hazard ratio for death, 2.05; 95% confidence interval, 1.30-3.24; P = 0.002 for Pro/Pro versus Arg/Arg). MDM2 GIG was associated with markedly reduced survival in squamous cell carcinoma (MS of 10.3 versus 49.4 months; adjusted hazard ratio for death, 7.9; 95% confidence interval, 2.4-26.0; P = 0.0007 for GIG versus TIT) but not in adenocarcinoma (SNP-histology interaction P = 0.004). Conclusions: In a large prospective cohort, p53 Arg72Pro Pro/Pro was associated with a 2-fold increased risk of death in all esophageal cancers, whereas MDM2 T309G GIG was associated with a 7-fold increased risk of death in squamous cell carcinoma. C1 [Cescon, David W.; Bradbury, Penelope A.; Hopkins, Jessica; Liu, Geoffrey] Univ Toronto, Princess Margaret Hosp, Div Med Oncol & Hematol, Toronto, ON M5S 1A1, Canada. [Ma, Clement; Xu, Wei] Univ Toronto, Princess Margaret Hosp, Biostat Unit, Toronto, ON M5S 1A1, Canada. [Liu, Geoffrey] Univ Toronto, Princess Margaret Hosp, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. [Asomaning, Kofi; Zhai, Rihong; Zhou, Wei; Wang, Zhaoxi; Su, Li; Christiani, David C.; Liu, Geoffrey] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kulke, Matthew] Dana Farber Canc Inst, Dept Med Oncol & Hematol, Boston, MA 02115 USA. [Kulke, Matthew] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Liu, G (reprint author), 610 Univ Ave,Suite 7-124, Toronto, ON M5G 2M9, Canada. EM Gepffrey.Liu@uhn.on.ca RI Liu, Geoffrey/N-4421-2016 FU NIH [R01 CA074386]; Doris Duke Charitable Foundation; Alan B. Brown Chair; Posluns Family Foundation; CIHR FX Grant support: NIH grant R01 CA074386, Doris Duke Charitable Foundation, Alan B. Brown Chair in Molecular Genomics, Posluns Family Foundation, and CIHR operating grant to Dr. G Liu. NR 34 TC 25 Z9 27 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2009 VL 15 IS 9 BP 3103 EP 3109 DI 10.1158/1078-0432.CCR-08-3120 PG 7 WC Oncology SC Oncology GA 440PL UT WOS:000265712100019 PM 19383811 ER PT J AU Qian, DZ Huang, CY O'Brien, CA Coleman, IM Garzotto, M True, LD Higano, CS Vessella, R Lange, PH Nelson, PS Beer, TM AF Qian, David Z. Huang, Chung-Ying O'Brien, Catherine A. Coleman, Ilsa M. Garzotto, Mark True, Lawrence D. Higano, Celestia S. Vessella, Robert Lange, Paul H. Nelson, Peter S. Beer, Tomasz M. TI Prostate Cancer-Associated Gene Expression Alterations Determined from Needle Biopsies SO CLINICAL CANCER RESEARCH LA English DT Article ID CDNA MICROARRAY ANALYSIS; COENZYME-A RACEMASE; ANDROGEN-RECEPTOR; MESSENGER-RNA; RADICAL PROSTATECTOMY; DISEASE RECURRENCE; AMPLIFIED RNA; PROTEIN; TISSUE; ID-1 AB Purpose: To accurately identify gene expression alterations that differentiate neoplastic from normal prostate epithelium using an approach that avoids contamination by unwanted cellular components and is not compromised by acute gene expression changes associated with tumor devascularization and resulting ischemia. Experimental Design: Approximately 3,000 neoplastic and benign prostate epithelial cells were isolated using laser capture microdissection from snap-frozen prostate biopsy specimens provided by 31 patients who subsequently participated in a clinical trial of preoperative chemotherapy. cDNA synthesized from amplified total RNA was hybridized to custom-made microarrays composed of 6,200 clones derived from the Prostate Expression Database. Expression differences for selected genes were verified using quantitative reverse transcription-PCR. Results: Comparative analyses identified 954 transcript alterations associated with cancer (q < 0.01%), including 149 differentially expressed genes with no known functional roles. Gene expression changes associated with ischemia and surgical removal of the prostate gland were absent. Genes up-regulated in prostate cancer were statistically enriched in categories related to cellular metabolism, energy use, signal transduction, and molecular transport. Genes down-regulated in prostate cancers were enriched in categories related to immune response, cellular responses to pathogens, and apoptosis. A heterogeneous pattern of androgen receptor expression changes was noted. In exploratory analyses, androgen receptor down-regulation was associated with a lower probability of cancer relapse after neoadjuvant chemotherapy followed by radical prostatectomy. Conclusions: Assessments of tumor phenotypes based on gene expression for treatment stratification and drug targeting of oncogenic alterations may best be ascertained using biopsy-based analyses where the effects of ischemia do not complicate interpretation. C1 [Beer, Tomasz M.] Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Qian, David Z.; O'Brien, Catherine A.; Beer, Tomasz M.] Oregon Hlth & Sci Univ, OHSU Canc Inst, Portland, OR 97239 USA. [Garzotto, Mark] Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97239 USA. [Garzotto, Mark] Portland VA Med Ctr, Portland, OR USA. [Huang, Chung-Ying; Coleman, Ilsa M.; Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA USA. [Huang, Chung-Ying; Coleman, Ilsa M.; Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA USA. [True, Lawrence D.; Nelson, Peter S.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Higano, Celestia S.; Nelson, Peter S.] Univ Washington, Div Oncol, Seattle, WA 98195 USA. [Vessella, Robert; Lange, Paul H.; Nelson, Peter S.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. RP Beer, TM (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Mail Code CR-145,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM beert@ohsu.edu FU NIH-National Cancer Institute [5R01CA119125]; Pacific Northwest Prostate Cancer Specialized Program of Research Excellence Career Development Award and Research Support [CA97186]; Department of Defense Fellowship [PC050489]; sanofi-aventis [16080]; OSI Pharmaceuticals [031.G0008]; Thomas and Gun Denhart FX NIH-National Cancer Institute grant 5R01CA119125, Pacific Northwest Prostate Cancer Specialized Program of Research Excellence Career Development Award and Research Support grant CA97186, Department of Defense Fellowship Award PC050489, sanofi-aventis 16080, OSI Pharmaceuticals 031.G0008, and Thomas and Gun Denhart. NR 53 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2009 VL 15 IS 9 BP 3135 EP 3142 DI 10.1158/1078-0432.CCR-08-1982 PG 8 WC Oncology SC Oncology GA 440PL UT WOS:000265712100023 PM 19366833 ER PT J AU Penney, KL Salinas, CA Pomerantz, M Schumacher, FR Beckwith, CA Lee, GS Oh, WK Sartor, O Ostrander, EA Kurth, T Ma, J Mucci, L Stanford, JL Kantoff, PW Hunter, DJ Stampfer, MJ Freedman, ML AF Penney, Kathryn L. Salinas, Claudia A. Pomerantz, Mark Schumacher, Fredrick R. Beckwith, Christine A. Lee, Gwo-Shu Oh, William K. Sartor, Oliver Ostrander, Elaine A. Kurth, Tobias Ma, Jing Mucci, Lorelei Stanford, Janet L. Kantoff, Philip W. Hunter, David J. Stampfer, Meir J. Freedman, Matthew L. TI Evaluation of 8q24 and 17q Risk Loci and Prostate Cancer Mortality SO CLINICAL CANCER RESEARCH LA English DT Article ID WIDE LINKAGE SCAN; CHROMOSOME 8Q24; RADICAL PROSTATECTOMY; AGGRESSIVENESS LOCI; GENETIC-VARIANTS; GLEASON SCORE; EARLY-ONSET; ASSOCIATION; CONFIRMATION; AMERICANS AB Purpose: Variants at chromosomal loci 8q24 and 17q are established risk factors for prostate cancer. Many studies have confirmed the findings for risk, but few have examined aggressiveness and other clinical variables in detail. Additionally, Gleason score is typically used as a surrogate for the primary end point of prostate cancer mortality. We investigated whether the 8q24 and 17q risk variants are associated with clinical variables as well as prostate cancer mortality. Experimental Design: In the Physicians' Health Study (1,347 cases and 1,462 controls), the Dana-Farber Harvard Cancer Center Specialized Program of Research Excellence (Gelb Center; 3,714 cases), and the Fred Hutchinson Cancer Research Center King County Case-Control Studies (1,308 cases and 1,266 controls), we examined eight previously identified 8q24 and 17q risk variants for association with prostate cancer mortality in men of European ancestry. We considered associations with other surrogate markers of prostate cancer aggressiveness, such as Gleason score, pathologic stage, prostate-specific antigen at diagnosis, and age at diagnosis. Results: Six of the eight variants were confirmed as prostate cancer risk factors. Several variants were nominally associated with age at diagnosis; when totaling all alleles for single nucleotide polymorphisms significantly associated with risk, each additional allele decreased age at diagnosis by an average of 6 months in the Physicians' Health Study (P = 0.0005) and 4 months in the Dana-Farber Harvard Cancer Center Specialized Program of Research Excellence (Gelb Center) cohort (P = 0.0016). However, there were no statistically significant associations with prostate cancer mortality. Conclusions: Our results suggest that the 8q24 and 17q prostate cancer risk variants may influence age at diagnosis but not disease aggressiveness. C1 [Pomerantz, Mark; Beckwith, Christine A.; Lee, Gwo-Shu; Oh, William K.; Kantoff, Philip W.; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Penney, Kathryn L.; Schumacher, Fredrick R.; Kurth, Tobias; Mucci, Lorelei; Hunter, David J.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kurth, Tobias] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA. [Ma, Jing; Mucci, Lorelei; Hunter, David J.; Stampfer, Meir J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Ma, Jing; Mucci, Lorelei; Hunter, David J.; Stampfer, Meir J.] Harvard Univ, Sch Med, Boston, MA USA. [Salinas, Claudia A.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Sartor, Oliver] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Ostrander, Elaine A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Hunter, David J.; Freedman, Matthew L.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Hunter, David J.; Freedman, Matthew L.] Harvard Univ, Cambridge, MA 02138 USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 710-C,44 Binney St, Boston, MA 02115 USA. EM freedman@broad.mit.edu RI Oh, William/B-9163-2012; Kurth, Tobias/A-9243-2012; OI Oh, William/0000-0001-5113-8147; Kurth, Tobias/0000-0001-7169-2620; Ostrander, Elaine/0000-0001-6075-9738 FU Dana-Farber Harvard Cancer Center Specialized Program [P50CA090381-06]; National Cancer Institute [CA56678, CA092579, CA097186, CA-34944, CA-40360, CA-097193]; National Heart, Lung, and Blood Institute [HL-26490, HL-34595]; National Research Service Awards [T32 CA009001-32, R25 CA098566] FX Dana-Farber Harvard Cancer Center Specialized Program of Research Excellence in Prostate Cancer grant P50CA090381-06. The Fred Hutchinson Cancer Research studies were supported by National Cancer Institute grants CA56678, CA092579, and CA097186. The Physicians' Health Study was supported by National Cancer Institute grants CA-34944, CA-40360, and CA-097193 and National Heart, Lung, and Blood Institute (Bethesda, MD) grants HL-26490 and HL-34595. K.L. Penney was supported by National Research Service Awards T32 CA009001-32 and R25 CA098566. F.R. Schumacher was supported by National Research Service Award T32 CA009001-32. NR 36 TC 34 Z9 34 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2009 VL 15 IS 9 BP 3223 EP 3230 DI 10.1158/1078-0432.CCR-08-2733 PG 8 WC Oncology SC Oncology GA 440PL UT WOS:000265712100035 PM 19366828 ER PT J AU Rao, SSC Kuo, B Mccallum, RW Chey, WD Dibaise, JK Hasler, WL Koch, KL Lackner, JM Miller, C Saad, R Semler, JR Sitrin, MD Wilding, GE Parkman, HP AF Rao, Satish S. C. Kuo, Braden Mccallum, Richard W. Chey, William D. Dibaise, John K. Hasler, William L. Koch, Kenneth L. Lackner, Jeffrey M. Miller, Carrie Saad, Richard Semler, Jack R. Sitrin, Michael D. Wilding, Gregory E. Parkman, Henry P. TI Investigation of Colonic and Whole-Gut Transit With Wireless Motility Capsule and Radiopaque Markers in Constipation SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID GASTROINTESTINAL TRANSIT; TIMES; PH; ABNORMALITIES; DISORDERS; HEALTHY; GENDER AB Background & Aims:: Colonic transit time (CTT) traditionally is assessed with radiopaque markers (ROMs), which requires radiation and is hindered by lack of standardization and compliance. We assessed regional and CTT with the SmartPill (SmartPill Corporation, Buffalo, NY), a new wireless pH and pressure recording capsule, in constipated and healthy subjects and compared this with ROM. Methods: Seventy-eight constipated (Rome II) and 87 healthy subjects ingested a 260-kcal meal, a ROM capsule, and the SmartPill. Subjects wore a data receiver and kept daily stool diaries for 5 days. SmartPill recordings assessed CTT, whole-gut transit time (WGTT), small-bowel transit time, and gastric emptying time. Abdominal radiographs on days 2 and 5 assessed ROM transit. Sensitivity/specificity and receiver operating characteristics (ROCs) of each technique and utility were compared. Results: Gastric emptying time, CTT, and WGTT were slower (P < .01) in constipated subjects than controls. CTT was slower in women than men (P = .02). Day 2 and day 5 ROM transits were slower (P < .001) in constipated subjects. Correlation of the SmartPill CTT with ROMs expelled on day 2/day 5 was r = 0.74/r = 0.69 in constipation, and r = 0.70/r = 0.40 in controls, respectively. The diagnostic accuracy of the SmartPill CTT to predict constipation from ROC was 0.73, with a specificity of 0.95. These were comparable with those of day 5 ROM (ROC, 0.71; specificity, 0.95). Conclusions: The SmartPill is a novel ambulatory technique of assessing regional (gastric, small bowel, colonic) and WGTT without radiation. It reveals hitherto unrecognized gender differences and upper-gut dysfunction in constipation. It correlates well with ROM and offers a standardized method of discriminating normal from slow colonic transit. C1 [Rao, Satish S. C.; Parkman, Henry P.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA. [Kuo, Braden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Mccallum, Richard W.] Univ Kansas, Med Ctr, Dept Med, Kansas City, KS 66103 USA. [Chey, William D.; Hasler, William L.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Dibaise, John K.] Mayo Clin, Dept Med, Scottsdale, AZ USA. [Koch, Kenneth L.; Semler, Jack R.] SmartPill Corp, Buffalo, NY USA. [Lackner, Jeffrey M.; Miller, Carrie; Sitrin, Michael D.; Wilding, Gregory E.] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA. [Saad, Richard] Temple Univ, Dept Med, Philadelphia, PA 19122 USA. RP Rao, SSC (reprint author), Univ Iowa, Hosp & Clin, 4612 JCP,200 Hawkins Dr, Iowa City, IA 52242 USA. EM satish-rao@uiowa.edu FU SmartPill Corporation, Buffalo, New York FX Grant support was received from the SmartPill Corporation, Buffalo, New York. NR 32 TC 119 Z9 124 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAY PY 2009 VL 7 IS 5 BP 537 EP 544 DI 10.1016/j.cgh.2009.01.017 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 445RS UT WOS:000266069800010 PM 19418602 ER PT J AU Bolon, MK Hooper, D Stevenson, KB Greenbaum, M Olsen, MA Herwaldt, L Noskin, GA Fraser, VJ Climo, M Khan, Y Vostok, J Yokoe, DS AF Bolon, Maureen K. Hooper, David Stevenson, Kurt B. Greenbaum, Maurice Olsen, Margaret A. Herwaldt, Loreen Noskin, Gary A. Fraser, Victoria J. Climo, Michael Khan, Yosef Vostok, Johanna Yokoe, Deborah S. CA Ctr Dis Control Prevention Epictr TI Improved Surveillance for Surgical Site Infections after Orthopedic Implantation Procedures: Extending Applications for Automated Data SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HOSPITAL DISCHARGE DIAGNOSES; POSTOPERATIVE INFECTIONS; ENHANCED IDENTIFICATION; SURGERY; BYPASS AB Background. Screening methods that use automated data may streamline surgical site infection (SSI) surveillance and improve the accuracy and comparability of data on SSIs. We evaluated the use of automated inpatient diagnosis codes and pharmacy data to identify SSIs after arthroplasty. Methods. This retrospective cohort study at 8 hospitals involved weighted, random samples of medical records from 2128 total hip arthroplasty (THA) procedures performed from 1 July 2002 through 30 June 2004, and 4194 total knee arthroplasty (TKA) procedures performed from 1 July 2003 through 30 June 2005. We compared routine surveillance with screening of inpatient pharmacy data and diagnoses codes followed by medical record review to confirm SSI status. Results. Records from 696 THA and 1009 TKA procedures were reviewed. The SSI rates were nearly double those determined by routine surveillance (1.32% [95% confidence interval, 0.83%-1.81%] vs. 0.75% for THA; 1.83% [95% confidence interval, 1.43%-2.23%] vs. 0.71% for TKA). An inpatient diagnosis code for infection within a year after the operation had substantially higher sensitivity (THA, 89%; TKA, 81%), compared with routine surveillance (THA, 56%; TKA, 39%). Adding antimicrobial exposure of >= 7 days after the procedure increased the sensitivity (THA, 93%; TKA, 86%). Record review confirmed SSIs after 51% of THAs and 55% of TKAs that met diagnosis code criteria and after 25% of THAs and 39% of TKAs that met antimicrobial exposure and/or diagnosis code criteria. Conclusions. Focused surveillance among a subset of patients who met diagnosis code screening criteria with or without the addition of antimicrobial exposure-based screening was more sensitive than routine surveillance for detecting SSIs after arthroplasty and could be an efficient and readily standardized adjunct to traditional methods. C1 [Bolon, Maureen K.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. [Hooper, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hooper, David] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Vostok, Johanna] Brigham & Womens Hosp, Harvard Pilgrim Hlth Care, Boston, MA 02115 USA. [Yokoe, Deborah S.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Yokoe, Deborah S.] Harvard Univ, Sch Med, Boston, MA USA. [Greenbaum, Maurice] N Shore Med Ctr, Salem, MA USA. [Stevenson, Kurt B.] Ohio State Univ, Med Ctr, Dept Clin Epidemiol, Columbus, OH 43210 USA. [Stevenson, Kurt B.; Khan, Yosef] Ohio State Univ, Dept Internal Med, Div Infect Dis, Coll Med, Columbus, OH 43210 USA. [Stevenson, Kurt B.; Khan, Yosef] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA. [Olsen, Margaret A.; Fraser, Victoria J.] Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63130 USA. [Fraser, Victoria J.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Herwaldt, Loreen] Univ Iowa, Coll Med, Iowa City, IA USA. [Herwaldt, Loreen] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. [Herwaldt, Loreen] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Climo, Michael] Hunter Holmes McGuire Vet Affairs Med Ctr, Richmond, VA USA. RP Bolon, MK (reprint author), Northwestern Univ, Feinberg Sch Med, Div Infect Dis, 645 N Michigan Ave Ste 900, Chicago, IL 60611 USA. EM m-bolon@northwestern.edu FU Centers for Disease Control and Prevention [UR8CCU-515081, U01-CI000328-03, 5U01-CI000333, U01-CI000583-01, UR8CCU-315346, UR8CCU-115079-01, 1U01-CI000344-03] FX We thank Farida Siddiqui, Pamela Fox, Kathleen Hoffman, Maureen Franklin, Christine Shanahan, Joyce Kelliher, Wendy Krauss, Dolores Suslak, Jean Pottinger, Marian Mamayek, Susan Marino, Melissa Ward, Jaclyn Hopp, and Cherie Hill for their contributions.; Financial support. Centers for Disease Control and Prevention (cooperative agreement awards UR8CCU-515081, U01-CI000328-03, 5U01-CI000333, U01-CI000583-01, UR8CCU-315346, UR8CCU-115079-01, and 1U01-CI000344-03). NR 19 TC 50 Z9 51 U1 1 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 MAY 1 PY 2009 VL 48 IS 9 BP 1223 EP 1229 DI 10.1086/597584 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 429CB UT WOS:000264897300011 PM 19335165 ER PT J AU Cadavid, D Londono, D AF Cadavid, D. Londono, D. TI Understanding tropism and immunopathological mechanisms of relapsing fever spirochaetes SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Review DE Borreliosis; brain; haemorrhage; interleukin-10; microglia; relapsing fever; review ID BORRELIA-TURICATAE; MOUSE MODEL; CERCOPITHECUS-AETHIOPS; PERSISTENT INFECTION; ANTIGENIC VARIATION; ARTHRITIS SEVERITY; NEUROTROPIC STRAIN; LYME BORRELIOSIS; B1B LYMPHOCYTES; BRAIN INFECTION AB Mice infected with relapsing fever (RF) spirochaetes survive recurrent waves of high-level bacteraemia with little, if any, clinical complications or tissue injury. In the absence of B-cells, peak bacteraemia does not resolve, resulting in multi-organ complications. During peak bacteraemia, large amounts of interleukin-10 (IL-10) are produced in blood and tissues. In mice unable to clear peak bacteraemia, exogenous IL-10 greatly reduced the clinical manifestations, serum levels of CXCL13, cerebral microgliosis, and the pathogen load. In contrast, IL-10 deficiency in mice unable to clear peak bacteraemia resulted in microvascular complications with distinct severities, depending on the serotype: serotype 2 (Bt2), which causes peak bacteraemia of c. 10(8)/mL, resulted in rapid death from subarachnoid and intraparenchymal haemorrhage; in contrast, serotype 1, which causes peak bacteraemia of c. 10(7)/mL, resulted in milder multi-organ haemorrhage and thrombosis. IL-10 deficiency also resulted in multi-organ haemorrhage and thrombosis with infarction in wild-type mice despite lower peak bacteraemia. Two mechanisms for pathogen control have been identified: antibody clearance of peak bacteraemia, and antibody-independent lowering of bacteraemia via phagocytosis in the spleen. IL-10 plays opposite roles in pathogen control, depending on the severity of bacteraemia: during persistent high bacteraemia, IL-10 helps to control it by protecting innate immune cells from apoptosis; in contrast, during transient peak bacteraemia, IL-10 slows down antibody-mediated clearance. A successful outcome from RF depends on a balanced immune response to clear bacteraemia while avoiding microvascular injury, in which production of IL-10, in response to the pathogen load, plays a critical role. C1 [Cadavid, D.; Londono, D.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP Cadavid, D (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St,Room 8301, Charlestown, MA 02129 USA. EM dcadavid@partners.org FU National Institute of Neurological Disorders and Stroke (NINDS) [R21NS057545] FX The research described in this review was supported by award number R21NS057545 from the National Institute of Neurological Disorders and Stroke (NINDS) to D. Cadavid. The content is solely the responsibility of the authors, and does not necessarily represent the views of the NINDS or the National Institutes of Health. D. Cadavid is currently a full-time employee of Biogen Idec. This review is not related to his employment at Biogen Idec. NR 40 TC 9 Z9 9 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD MAY PY 2009 VL 15 IS 5 BP 415 EP 421 DI 10.1111/j.1469-0691.2009.02785.x PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 446GQ UT WOS:000266110500005 PM 19489924 ER PT J AU Tamaki, M Matsuoka, T Nittono, H Hori, T AF Tamaki, Masako Matsuoka, Tatsuya Nittono, Hiroshi Hori, Tadao TI Activation of fast sleep spindles at the premotor cortex and parietal areas contributes to motor learning: A study using sLORETA SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Sleep; Memory; Learning; Sleep spindle; Fast spindle; Premotor cortex; Parietal associative area ID RESOLUTION ELECTROMAGNETIC TOMOGRAPHY; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; CORTICAL SOURCES; BRAIN; MEMORY; PERFORMANCE; NEOCORTEX; LORETA; SKILL AB Objective: The present study examined whether slow and/or fast sleep spindles are related to visuomotor learning, by examining the densities of current sleep spindle activities. Methods: Participants completed a visuomotor task before and after sleep on the learning night. This task was not performed on the non-learning night. Standard polysomnographic recordings were made. After the amplitudes of slow and fast spindles were calculated, sLORETA was used to localize the source of slow and fast spindles and to investigate the relationship between spindle activity and motor learning. Results: Fast spindle amplitude was significantly larger on the learning than on the non-learning nights, particularly at the left frontal area. sLORETA revealed that fast spindle activities in the left frontal and left parietal areas were enhanced when a new visuomotor skill was learned. There were no significant learning-dependent changes in slow spindle activity. Conclusions: Fast spindle activity increases in cortical areas that are involved in learning a new visuomotor skill. The thalamocortical network that underlies the generation of fast spindles may contribute to the synaptic plasticity that occurs during sleep. Significance: Activity of fast sleep spindles is a possible biomarker of memory deficits. (C) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Hori, Tadao] Fukuyama Transporting Shibuya Longev Hlth Fdn, Sleep Res Inst, Hiroshima 7210961, Japan. [Tamaki, Masako] Waseda Univ, Fac Sport Sci, Tokorozawa, Saitama 3591192, Japan. [Tamaki, Masako] Japan Soc Promot Sci, Chiyoda Ku, Tokyo, Japan. [Tamaki, Masako] Massachusetts Gen Hosp, Dept Radiol, Atinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Tamaki, Masako] Harvard Univ, Sch Med, Boston, MA USA. [Matsuoka, Tatsuya] Hiroshima Univ, Fac Integrated Arts & Sci, Hiroshima 730, Japan. [Nittono, Hiroshi; Hori, Tadao] Hiroshima Univ, Grad Sch Integrated Arts & Sci, Hiroshima 730, Japan. RP Hori, T (reprint author), Fukuyama Transporting Shibuya Longev Hlth Fdn, Sleep Res Inst, 2-5-22 Myojincho, Hiroshima 7210961, Japan. EM tdhori@hiroshima-u.ac.jp RI Nittono, Hiroshi/C-4043-2009 OI Nittono, Hiroshi/0000-0001-5671-609X FU Japan Society for the Promotion of Science (JSPS) [06J08283] FX This study was supported by the Grant-in-Aid for JSPS Fellows from the Japan Society for the Promotion of Science (JSPS) (No. 06J08283). NR 69 TC 36 Z9 37 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD MAY PY 2009 VL 120 IS 5 BP 878 EP 886 DI 10.1016/j.clinph.2009.03.006 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 455JM UT WOS:000266755200007 PM 19376746 ER PT J AU Forsythe, B Lavery, KP Warner, JJP AF Forsythe, Brian Lavery, Kyle P. Warner, Jon J. P. TI Acromionectomy and Deltoid Deficiency: A Solution SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ROTATOR CUFF AB Deltoid insufficiency after iatrogenic or traumatic acromionectomy results from separation of the deltoid from its origin and mechanical fulcrum. Subsequent retraction of the tendon and formation of subdeltoid adhesions to the cuff and humerus result in stiffness and pain. We evaluated clinical outcomes of patients treated with autogenous tricortical iliac crest bone graft combined with deltoid reconstruction or deltoidplasty for deltoid insufficiency after acromionectomy. We retrospectively reviewed four patients, three males, and one female treated with deltoidplasty reconstructions as revision surgery. Their mean age was 41 years, and the minimum followup was 41 months (mean, 50 months; range, 41-66 months). There were three work-related injuries. Outcomes evaluated were pain relief (visual analog score), American Shoulder and Elbow Surgeons score, cosmesis, and complications. The mean pain score improved from 8 (range, 3-10) preoperatively to 1 (range, 0-3) postoperatively. The mean American Shoulder and Elbow Surgeons score improved from 31 +/- A 14 to 68 +/- A 13. One patient required revision deltoidplasty for abductor weakness. Three patients underwent hardware removal. One patient who underwent concurrent latissimus dorsi transfer had limited functional improvement but decreased pain. Two patients had improved cosmesis. All had CT scans with three-dimensional reconstructions documenting union. All patients stated they would undergo the procedure again. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. C1 [Forsythe, Brian; Lavery, Kyle P.; Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Forsythe, B (reprint author), Massachusetts Gen Hosp, Harvard Shoulder Serv, 55 Fruit St,Suite 3200,3G,Room 3-044, Boston, MA 02114 USA. EM JWARNER@partners.org NR 12 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 2009 VL 467 IS 5 BP 1334 EP 1340 DI 10.1007/s11999-008-0638-0 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 428NE UT WOS:000264854300031 PM 19037708 ER PT J AU Boland, GWL AF Boland, G. W. L. TI The impact of teleradiology in the United States over the last decade: driving consolidation and commoditization of radiologists and radiology services SO CLINICAL RADIOLOGY LA English DT Editorial Material ID AGE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Boland, GWL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM gboland@partners.org NR 18 TC 11 Z9 11 U1 0 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD MAY PY 2009 VL 64 IS 5 BP 457 EP 460 DI 10.1016/j.crad.2008.11.010 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 442YE UT WOS:000265876000001 PM 19348838 ER PT J AU Sorond, FA Shaffer, ML Kung, AL Lipsitz, LA AF Sorond, Farzaneh A. Shaffer, Michele L. Kung, Andrew L. Lipsitz, Lewis A. TI Desferroxamine infusion increases cerebral blood flow: a potential association with hypoxia-inducible factor-1 SO CLINICAL SCIENCE LA English DT Article DE cerebral blood flow; desferroxamine; hypoxia-inducible factor-1 (HIF-1); transcranial Doppler ultrasound ID CHELATING AGENT DEFEROXAMINE; DELAYED NEURONAL DEATH; NEONATAL-RAT BRAIN; SUBARACHNOID HEMORRHAGE; ENDOTHELIAL-CELLS; HYPERBARIC-OXYGEN; GENE-EXPRESSION; ISCHEMIC TOLERANCE; O-2 HOMEOSTASIS; APOPTOTIC GENES AB Finding an effective means to improve cerebral perfusion during hypoxic/ischaemic stress is essential for neuroprotection. Studies in animal models of stroke have shown that desferroxamine activates HIF-1 (hypoxia-inducible factor-1), reduces brain damage and promotes functional recovery. The present study was designed to investigate the effects of desferroxamine infusion on the cerebral circulation in humans. Fifteen volunteers were enrolled in a randomized double-blind placebo-controlled crossover study. We measured cerebral blood flow velocity by transcranial Doppler ultrasonography in the middle cerebral artery, arterial blood pressure, end-tidal CO(2), as well as HIF-1 protein and serum lactate dehydrogenase concentrations in response to 8 h of desferroxamine compared with placebo infusion. Cerebrovascular resistance was calculated from the ratio of steady-state beat-to-beat values for blood pressure to blood flow velocity. We found that desferroxamine infusion was associated with a significant cerebral vasodilation. Moreover, decreased cerebrovascular resistance was temporally correlated with an increased HIF-1 protein concentration as well as HIF-1 transcriptional activation, as measured by serum lactate dehydrogenase concentration. The findings of the present study provide preliminary data suggesting that activators of HIF-1, such as desferroxamine, may protect neurons against ischaemic injury by dilating cerebral vessels and enhancing cerebral perfusion. C1 [Sorond, Farzaneh A.] Brigham & Womens Hosp, Dept Neurol, Stroke Div, Boston, MA 02115 USA. [Sorond, Farzaneh A.; Lipsitz, Lewis A.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA. [Shaffer, Michele L.] Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA 17033 USA. [Kung, Andrew L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lipsitz, Lewis A.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Sorond, FA (reprint author), Brigham & Womens Hosp, Dept Neurol, Stroke Div, 75 Francis St, Boston, MA 02115 USA. EM fsorond@partners.org OI Kung, Andrew/0000-0002-9091-488X FU National Institute on Aging [AG004390, AG08812, AG05134]; Mentored Clinical Scientist K12 Award from the National Institute on Aging [AG00294] FX This work was supported by the National Institute on Aging [grant numbers AG004390, AG08812, AG05134]. F.A.S. is the recipient of Mentored Clinical Scientist K12 Award from the National Institute on Aging [grant number AG00294]. L. A. L. holds the Irving and Edyth S. Usen and Family Chair in Geriatric Medicine at Hebrew SeniorLife. NR 54 TC 8 Z9 9 U1 0 U2 3 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD MAY PY 2009 VL 116 IS 9-10 BP 771 EP 779 DI 10.1042/CS20080320 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 443BQ UT WOS:000265885600008 PM 19014354 ER PT J AU O'Leary, JG Yachimski, PS Friedman, LS AF O'Leary, Jacqueline G. Yachimski, Patrick S. Friedman, Lawrence S. TI Surgery in the Patient with Liver Disease SO CLINICS IN LIVER DISEASE LA English DT Article DE Cirrhosis; Surgery; MELD score; Child class; Liver disease ID INTRAHEPATIC PORTOSYSTEMIC SHUNT; GASTRIC BYPASS-SURGERY; HEPATOCELLULAR-CARCINOMA; CIRRHOTIC-PATIENTS; UNITED-STATES; LAPAROSCOPIC CHOLECYSTECTOMY; OBSTRUCTIVE-JAUNDICE; HEPATIC RESECTION; HEPATORENAL-SYNDROME; RISK-FACTORS AB The advent of liver transplantation has greatly improved the long-term survival of patients with decompensated cirrhosis, and surgery is now performed more frequently in patients with advanced liver disease. The estimation of perioperative mortality is limited by the retrospective nature of and biased patient selection in the available clinical studies. The overall experience is that, in patients with cirrhosis, use of the Child classification and Model for End-Stage Liver Disease (MELD) score provides a reasonably precise estimation of perioperative mortality. Careful preoperative preparation and monitoring to detect complications early in the postoperative course are essential to improve outcomes. C1 [Yachimski, Patrick S.; Friedman, Lawrence S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [O'Leary, Jacqueline G.] Baylor Univ, Med Ctr, Div Hepatol, Dept Internal Med, Dallas, TX 75246 USA. [Yachimski, Patrick S.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Yachimski, Patrick S.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Friedman, Lawrence S.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02110 USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. [Friedman, Lawrence S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Friedman, LS (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. EM lfriedman@partners.org NR 92 TC 18 Z9 18 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1089-3261 J9 CLIN LIVER DIS JI Clin. Liver Dis. PD MAY PY 2009 VL 13 IS 2 BP 211 EP + DI 10.1016/j.cld.2009.02.002 PG 22 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 460SK UT WOS:000267207200005 PM 19442915 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI A New Era for CNS Spectrums SO CNS SPECTRUMS LA English DT Editorial Material ID CONFLICTS-OF-INTEREST; DEPRESSION; NEUROGENESIS; POLYMORPHISM; PSYCHIATRY C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAY PY 2009 VL 14 IS 5 BP 232 EP 233 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 448YL UT WOS:000266297800001 PM 19407720 ER PT J AU Busner, J Targum, SD Miller, DS AF Busner, Joan Targum, Steven D. Miller, David S. TI The Clinical Global Impressions scale: errors in understanding and use SO COMPREHENSIVE PSYCHIATRY LA English DT Article; Proceedings Paper CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol ID PLACEBO-RESPONSE; DEPRESSION; SCHIZOPHRENIA; HALOPERIDOL; OLANZAPINE; DISORDERS; PSYCHOSIS; TRIALS AB Objective: The Clinical Global Impressions Severity and Improvement scales (CGI-S and CGI-I) are widely included as efficacy data in psychopharmacology new drug application submissions. This study was conducted to determine the extent to which clinical trials investigators included information unrelated to efficacy in their CGI ratings. Method: Forty-five principal investigators provided CGI-S and CGI-I ratings of narratives of patients with major depressive disorder or generalized anxiety disorder. Investigators were blindly randomized to receive narratives that either did (experimental) or did not (control) contain indication-unrelated medical or psychiatric adverse events. Investigators then completed a survey assessing CGI-S and CGI-I rating patterns. Results: CGI-S and CGI-I ratings were significantly more severe and less improved when the narratives contained medical and psychiatric adverse events unrelated to the diseases under study (major depressive disorder and generalized anxiety disorder) than when the narratives did not (Ps < .04). In response to the survey, 46% and 56% of investigators reported that a psychiatric adverse event unrelated to the disease under study would not affect their CGI-S and CGI-I ratings, respectively. Although 87% of investigators reported that their CGI-S and CGI-I ratings Would not be affected by a medical adverse event, actual CGI-S ratings were significantly more severe when all unrelated medical adverse event was described as occurring than when it vas not (P < .03). Conclusion: Clinical trials investigators' inclusion of indication-irrelevant adverse events threatens the validity of the CGI as an efficacy measure and may contribute to failure to detect efficacy signals in psychopharmacology clinical trials. (c) 2009 Elsevier Inc. All rights reserved. C1 [Busner, Joan; Targum, Steven D.; Miller, David S.] United BioSource Corp, Wayne, PA 19087 USA. [Targum, Steven D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Targum, Steven D.] Oxford BioSci Partners, Boston, MA USA. [Busner, Joan] Penn State Coll Med, Dept Psychiat, Hershey, PA USA. RP Busner, J (reprint author), United BioSource Corp, Wayne, PA 19087 USA. EM joan.busner@unitedbiosource.com NR 18 TC 23 Z9 26 U1 1 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 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAY-JUN PY 2009 VL 50 IS 3 BP 257 EP 262 DI 10.1016/j.comppsych.2008.08.005 PG 6 WC Psychiatry SC Psychiatry GA 439VL UT WOS:000265655400011 PM 19374971 ER PT J AU Fraguas, R Telles, RMD Alves, TCTF Andrei, AM Rays, J Iosifescu, DV Wajngarten, M AF Fraguas, Renerio da Silva Telles, Renata Martinho Toledo Ferraz Alves, Tania Correa Andrei, Anna Maria Rays, Jairo Iosifescu, Dan V. Wajngarten, Mauricio TI A double-blind, placebo-controlled treatment trial of citalopram for major depressive disorder in older patients with heart failure: The relevance of the placebo effect and psychological symptoms SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Heart failure; Depression; Elderly; Double-blind; Randomized controlled trial; Placebo effect ID QUALITY-OF-LIFE; SEROTONIN REUPTAKE INHIBITORS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; ELDERLY-PATIENTS; MILD DEPRESSION; PRIMARY-CARE; PAROXETINE; NORTRIPTYLINE; MORTALITY AB Background: Little is known about the treatment of depression in older patients with heart failure. This Study was developed to investigate the effectiveness of antidepressant treatment for major depressive disorder (MDD) in the elderly with heart failure. Methods: We enrolled 72 older outpatients with ejection fraction < 50 and diagnosed with MDD by the structured clinical interview for DSM-IV. Thirty-seven patients, 19 on citalopram and 18 on placebo, initiated an 8-week double-blind treatment phase. Measurements were performed with the 31-item Hamilton Rating Scale for Depression (Ham-D-31), the Montgomery-Asberg rating scale (MADRS) and the Systematic Assessment for Treatment Emergent Effects (SAFTEE). A psychiatrist followed up the patients weekly, performing a consultation for about 20 min to field complaints after the measurements. Results: A trend toward superiority of citalopram over placebo in reducing depression was observed in MADRS scores (15.05 + 9.74 vs 9.44 + 9.25, P = .082) but not on HAM-D scores. The depressive symptomatology significantly decreased in both groups (P < .001). The high rate of placebo response during the double-blind phase (56.3%) led us to conclude the study at the interim analysis with 37 patients. Conclusion: Citalopram treatment of MDD in older patients with heart failure is well-tolerated with low rates of side effects, but was not significantly more effective than placebo in the treatment of depression. Weekly psychiatric follow-up including counseling may contribute to the improvement of depression in this population. Scales weighted on psychological symptoms such as the MADRS are possibly better suited to measure depression severity and improvement in patients with heart failure. (C) 2009 Elsevier Inc. All rights reserved. C1 [Fraguas, Renerio; da Silva Telles, Renata Martinho; Toledo Ferraz Alves, Tania Correa] Univ Sao Paulo, Fac Med, Hosp Clin, Dept & Inst Psychiat, BR-05014010 Sao Paulo, Brazil. [Andrei, Anna Maria; Rays, Jairo; Wajngarten, Mauricio] Univ Sao Paulo, Fac Med, Clin Hosp, Inst Heart, BR-05014010 Sao Paulo, Brazil. [Iosifescu, Dan V.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Depress Clin & Res Program, Boston, MA 02115 USA. RP Fraguas, R (reprint author), Univ Sao Paulo, Fac Med, Hosp Clin, Dept & Inst Psychiat, Rua Ovidio Pires Campos S-N, BR-05014010 Sao Paulo, Brazil. EM rfraguas@hcnet.usp.br RI Wajngarten, Mauricio/G-3702-2012; Alves, Tania/H-3416-2013; Andrei, Anna Maria/P-5207-2015; Alves, Tania/B-6571-2008 OI Alves, Tania/0000-0003-3402-9656; Alves, Tania/0000-0003-3402-9656 FU State of Sao Paulo Research Foundation (FAPESP), Brazil [1999/04993-5] FX This study was supported by the State of Sao Paulo Research Foundation (FAPESP), Brazil, grants 1999/04993-5. NR 51 TC 20 Z9 21 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAY PY 2009 VL 30 IS 3 BP 205 EP 211 DI 10.1016/j.cct.2009.01.007 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 454HC UT WOS:000266672000004 PM 19470312 ER PT J AU Pukkila-Worley, R Holson, E Wagner, F Mylonakis, E AF Pukkila-Worley, R. Holson, E. Wagner, F. Mylonakis, E. TI Antifungal Drug Discovery through the Study of Invertebrate Model Hosts SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE Novel antifungal compounds; compound screens; caffeic acid phenethyl ester (CAPE); Candida albicans; Cryptococcus neoformans; Caenorhabditis elegans ID ACID PHENETHYL ESTER; HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD-STREAM INFECTIONS; NF-KAPPA-B; ANTIMICROBIAL SURVEILLANCE PROGRAM; NEMATODE CAENORHABDITIS-ELEGANS; VULVO-VAGINAL CANDIDIASIS; INTENSIVE-CARE UNITS; CRYPTOCOCCUS-NEOFORMANS; VANCOUVER-ISLAND AB There is an urgent need for new antifungal agents that are both effective and non-toxic in the therapy of systemic mycoses. The model nematode Caenorhabditis elegans has been used both to elucidate evolutionarily conserved components of host-pathogen interactions and to screen large chemical libraries for novel antimicrobial compounds. Here we review the use of C. elegans models in drug discovery and discuss caffeic acid phenethyl ester, a novel antifungal agent identified using an in vivo screening system. C. elegans bioassays allow high-throughput screens of chemical libraries in vivo. This whole-animal system may enable the identification of compounds that modulate immune responses or affect fungal virulence factors that are only expressed during infection. In addition, compounds can be simultaneously screened for antifungal efficacy and toxicity, which may overcome one of the main obstacles in current antimicrobial discovery. A pilot screen for antifungal compounds using this novel C. elegans system identified 15 compounds that prolonged survival of nematodes infected with the medically important human pathogen Candida albicans. One of these compounds, caffeic acid phenethyl ester (CAPE), was an effective antifungal agent in a murine model of systemic candidiasis and had in vitro activity against several fungal species. Interestingly, CAPE is a potent immunomodulator in mammals with several distinct mechanisms of action. The identification of CAPE in a C. elegans screen supports the hypothesis that this model can identify compounds with both antifungal and host immunomodulatory activity. C1 [Pukkila-Worley, R.; Mylonakis, E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Holson, E.; Wagner, F.] MIT, Broad Inst, Cambridge, MA 02142 USA. [Holson, E.; Wagner, F.] Harvard Univ, Cambridge, MA 02142 USA. RP Mylonakis, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org FU Irvington Institute; Astellas Pharma Inc. FX This work was supported by a Fellowship in General Immunology from the Irvington Institute (to R. P. W.). E. M. has served as a consult ant for Biogen Idec., received research support from Astellas Pharma Inc. and is a member of the Speaker's Bureau for Pfizer Inc. The other authors report no potential conflicts of interest. NR 88 TC 22 Z9 24 U1 2 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD MAY PY 2009 VL 16 IS 13 BP 1588 EP 1595 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 440HZ UT WOS:000265692700002 PM 19442135 ER PT J AU Norden, AD Drappatz, J Wen, PY AF Norden, Andrew D. Drappatz, Jan Wen, Patrick Y. TI Advances in meningioma therapy SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL; INTRACRANIAL MENINGIOMAS; MALIGNANT MENINGIOMA; RECURRENT MENINGIOMA; ATYPICAL MENINGIOMA; ANAPLASTIC MENINGIOMAS; SPORADIC MENINGIOMAS; PERITUMORAL EDEMA; INTERFERON-ALPHA AB Meningiomas are the most common primary brain tumors in adults. Most of them are benign (World Health Organization [WHO] grade I), slow-growing lesions, but some are classified as atypical (WHO grade II) or malignant (WHO grade III). Surgical resection is curative when complete removal of a benign meningioma is possible. Incompletely resected tumors and high-grade lesions are frequently treated with fractionated radiotherapy or stereotactic radiosurgery. Radiotherapy effectively reduces recurrence rates with limited toxicity. High-grade meningiomas tend to recur following maximal treatment with surgery and radiation. Chemotherapeutic agents, including hydroxyurea, have been used for recurrent disease with marginal efficacy. As the molecular pathogenesis of meningiomas is elucidated, targeted drug therapies may prove useful. Angiogenesis inhibitors, agents that target fundamental cell signaling pathways, somatostatin analogues, and a variety of other molecular treatments appear promising. C1 [Wen, Patrick Y.] Ctr Neurooncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wen, PY (reprint author), Ctr Neurooncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org FU Pfizer; Novartis FX Dr. Noden has served as a consultant for Schering- Plough. Dr. Drappatz has received research support from ScheringPlough. Dr. Wen has received research support from Pfizer and Novartis. NR 87 TC 47 Z9 49 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 EI 1534-6293 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD MAY PY 2009 VL 9 IS 3 BP 231 EP 240 DI 10.1007/s11910-009-0034-5 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 428XO UT WOS:000264885600007 PM 19348712 ER PT J AU Gerstner, ER Sorensen, G Jain, RK Batchelor, TT AF Gerstner, Elizabeth R. Sorensen, Gregory Jain, Rakesh K. Batchelor, Tracy T. TI Anti-vascular endothelial growth factor therapy for malignant glioma SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review ID TYROSINE KINASE INHIBITOR; BEVACIZUMAB PLUS IRINOTECAN; TUMOR-GROWTH; FACTOR-RECEPTOR; GLIOBLASTOMA-MULTIFORME; VEGF-TRAP; IN-VIVO; RECURRENT GLIOBLASTOMA; RADIATION-THERAPY; CLINICAL-TRIALS AB Glioblastomas are among the most vascular tumors because they oversecrete vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis. Consequently, new drug regimens are being developed to target the VEGF signaling pathway in an attempt to halt tumor growth. Antibodies that bind VEGF, decoy molecules that sequester VEGF, and small molecule tyrosine kinase inhibitors that block receptor activation are being tested. Preliminary results with these agents have been promising, with prolonged progression-free survival reported. The antipermeability effects of anti-VEGF agents have important consequences for tumor imaging and for patient quality of life by decreasing corticosteroid dependence. However, because most patients eventually relapse, more work is needed to understand mechanisms of disease escape, including vascular cooption of native brain blood vessels. C1 [Gerstner, Elizabeth R.] Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM egerstner@partners.org FU NCI NIH HHS [P01 CA080124] NR 53 TC 8 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD MAY PY 2009 VL 9 IS 3 BP 254 EP 262 DI 10.1007/s11910-009-0037-2 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 428XO UT WOS:000264885600010 PM 19348715 ER PT J AU Chan, JA Kulke, MH AF Chan, Jennifer A. Kulke, Matthew H. TI Progress in the Treatment of Neuroendocrine Tumors SO CURRENT ONCOLOGY REPORTS LA English DT Article AB Traditional treatments for patients with advanced neuroendocrine tumors include surgical debulking, hepatic embolization, somatostatin analogues, and interferon-alpha. Patients with pancreatic neuroendocrine tumors also may benefit from treatment with the alkylating agents streptozocin or temozolomide. In recent years, several promising new approaches have been investigated in patients with advanced neuroendocrine tumors. One such approach has been the use of radiopeptide therapy targeting somatostatin receptors. Additionally, agents targeting the vascular endothelial growth factor pathway and mammalian target of rapamycin have shown preliminary evidence of activity and are currently being evaluated in large randomized studies. C1 [Chan, Jennifer A.] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. RP Chan, JA (reprint author), Dana Farber Canc Inst, Gastrointestinal Canc Ctr, 44 Binney St, Boston, MA 02115 USA. EM jang@partners.org FU National Cancer Institute [P50 CA127003]; Caring for Carcinoid Foundation; Stephen and Caroline Kaufer fund for neuroendocrine tumor research FX This work was supported by National Cancer Institute grant P50 CA127003 (DF/HCC SPORE in Gastrointestinal Cancer). Additional support was provided by the Caring for Carcinoid Foundation, the Stephen and Caroline Kaufer fund for neuroendocrine tumor research, and Mr. Saul and Gitta Kurlat. We thank Lindy Morde for assistance in the preparation of the manuscript. NR 49 TC 12 Z9 13 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 EI 1534-6269 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD MAY PY 2009 VL 11 IS 3 BP 193 EP 199 PG 7 WC Oncology SC Oncology GA V16BG UT WOS:000207844500005 PM 19336011 ER PT J AU Courtney, KD Choueiri, TK AF Courtney, Kevin D. Choueiri, Toni K. TI Optimizing Recent Advances in Metastatic Renal Cell Carcinoma SO CURRENT ONCOLOGY REPORTS LA English DT Article AB The past few years have seen dramatic advances in the treatment of metastatic renal cell carcinoma (RCC). Dissection of the molecular pathways that regulate proliferation, apoptosis, and angiogenesis has led to the development of targeted therapies such as the receptor tyrosine kinase inhibitors sunitinib and sorafenib, the anti-vascular endothelial growth factor antibody bevacizumab, and a class of rapamycin analogues including everolimus and temsirolimus. Each of these agents has demonstrated clinical efficacy in patients with metastatic RCC. The challenge before us is to expand on these successes by identifying which patients will best respond to these targeted therapies, optimizing the proper combination or sequence of available therapies, developing agents with improved side effect profiles, and identifying novel therapeutic targets to expand our armamentarium in the treatment of RCC. C1 [Choueiri, Toni K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, 44 Binney St, Boston, MA 02115 USA. EM toni_choueiri@dfci.harvard.edu FU Genentech FX Dr. Choueiri has served on advisory boards of Genentech, Pfizer, Bayer/Onyx, Abbott, GlaxoSmithKline, and Novartis. Dr. Courtney receives grant support from a Kidney Cancer Career Development Award funded by Genentech. NR 55 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD MAY PY 2009 VL 11 IS 3 BP 218 EP 226 PG 9 WC Oncology SC Oncology GA V16BG UT WOS:000207844500008 PM 19336014 ER PT J AU Elfiky, AA Rosenberg, JE AF Elfiky, Aymen A. Rosenberg, Jonathan E. TI Targeting Angiogenesis in Bladder Cancer SO CURRENT ONCOLOGY REPORTS LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TRANSITIONAL-CELL CARCINOMA; RECEPTOR MONOCLONAL-ANTIBODY; ONCOLOGY-GROUP ECOG; MICROVESSEL DENSITY; FACTOR EXPRESSION; INTERSTITIAL HYPERTENSION; NEOADJUVANT CHEMOTHERAPY; COLORECTAL-CANCER; INHIBITOR TNP-470 AB In most cases, death from bladder cancer results from metastatic disease. Understanding the closely linked mechanisms of invasion, metastasis, and angiogenesis in bladder cancer has allowed development of new therapeutic strategies that may lead to improvements in patient survival. Vascular endothelial growth factor levels appear to be prognostic for outcomes in advanced bladder cancer, and preclinical evaluation of angiogenesis inhibition demonstrates anticancer activity. Antiangiogenic agents such as sunitinib, sorafenib, and bevacizumab are being tested in advanced bladder cancer. This review highlights the key developments in antiangiogenic therapy as it relates to bladder cancer treatment. C1 [Rosenberg, Jonathan E.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Rosenberg, JE (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St,D1230, Boston, MA 02115 USA. EM jonathan_rosenberg@dfci.harvard.edu NR 59 TC 23 Z9 23 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 EI 1534-6269 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD MAY PY 2009 VL 11 IS 3 BP 244 EP 249 PG 6 WC Oncology SC Oncology GA V16BG UT WOS:000207844500011 PM 19336017 ER PT J AU Pratt, DS AF Pratt, Daniel S. TI Hepatitis B: significant advances and unmet challenges SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material ID VIRUS INFECTION; MANAGEMENT C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Pratt, DS (reprint author), Massachusetts Gen Hosp, GI Unit, Blake 4,55 Fruit St, Boston, MA 02114 USA. EM dspratt@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD MAY PY 2009 VL 25 IS 3 BP 173 EP 174 DI 10.1097/MOG.0b013e32832a57e9 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 443EH UT WOS:000265892500001 PM 19396953 ER PT J AU Minguez, B Tovar, V Chiang, D Villanueva, A Llovet, JM AF Minguez, Beatriz Tovar, Victoria Chiang, Derek Villanueva, Augusto Llovet, Josep M. TI Pathogenesis of hepatocellular carcinoma and molecular therapies SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE hepatocellular carcinoma; molecular classification; molecular targeted therapies; signaling pathways ID GROWTH-FACTOR RECEPTOR; PHASE-II TRIAL; GENE-EXPRESSION; BETA-CATENIN; THERAPEUTIC TARGETS; INDUCED APOPTOSIS; DOWN-REGULATION; HEPATOMA-CELLS; LIVER-CANCER; RISK-FACTORS AB Purpose of review Over the past decades, advances in the knowledge of the molecular pathogenesis of hepatocellular carcinoma (HCC) have allowed significant improvements in the therapeutic management of this devastating disease. Several investigations have established the role of aberrant activation of major intracellular signaling pathways during human hepatocarcinogenesis. Genome-wide analysis of DNA copy number changes and gene expression led to the identification of gene signatures and novel targets for cancer treatment. Numerous attempts have tried to develop a molecular classification of HCC. This review aims to summarize the most relevant genetic alterations and pathways involved in the development and progression of HCC, providing an overview of the molecular targeted therapies tested so far in human HCC. Recent findings The discovery of sorafenib, a multikinase inhibitor, as a treatment with survival benefits in patients with advanced HCC, has become a major breakthrough in the clinical management of HCC. For the first time, a molecular therapy was able to demonstrate significant efficacy for the treatment of HCC patients. New guidelines have established the ideal endpoints for the design of clinical trials for HCC. At last, a molecular classification of HCC based on genome-wide investigations, able to identify patient subclasses according to drug sensitivity will lead to a more personalized medicine. Summary In this review, we provide a comprehensive analysis of the underlying molecular mechanisms leading to human hepatocarcinogenesis, providing the scientific rationale for the development of new therapeutic targets. C1 [Minguez, Beatriz; Llovet, Josep M.] Mt Sinai Sch Med, Div Liver Dis, Mt Sinai Liver Canc Program, New York, NY 10029 USA. [Tovar, Victoria; Villanueva, Augusto; Llovet, Josep M.] Hosp Clin Barcelona, CIBERehd, IDIBAPS,HCC Translat Res Lab, BCLC Grp,Liver Unit, Barcelona, Spain. [Chiang, Derek] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chiang, Derek] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Llovet, Josep M.] ICREA, Barcelona, Spain. RP Llovet, JM (reprint author), Mt Sinai Sch Med, Div Liver Dis, Mt Sinai Liver Canc Program, Madison Ave 1425,11F-70,Box 1123, New York, NY 10029 USA. EM Josep.Llovet@mssm.edu RI Augusto, Villanueva/F-9378-2012; Minguez, Beatriz/N-4456-2014; Llovet, Josep M /D-4340-2014; OI Augusto, Villanueva/0000-0003-3585-3727; Minguez, Beatriz/0000-0002-7276-9666; Llovet, Josep M /0000-0003-0547-2667; Chiang, Derek/0000-0002-1131-6065 NR 96 TC 83 Z9 88 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD MAY PY 2009 VL 25 IS 3 BP 186 EP 194 DI 10.1097/MOG.0b013e32832962a1 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 443EH UT WOS:000265892500004 PM 19387255 ER PT J AU Perkins, BA Krolewski, AS AF Perkins, Bruce A. Krolewski, Andrzej S. TI Early nephropathy in type 1 diabetes: the importance of early renal function decline SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE diabetic nephropathy; early renal function decline; microalbuminuria; type 1 diabetes ID GLOMERULAR-FILTRATION-RATE; URINARY ALBUMIN EXCRETION; C-REACTIVE PROTEIN; SERUM URIC-ACID; CYSTATIN-C; NONPROTEINURIC PATIENTS; SERIAL MEASUREMENTS; TNF-ALPHA; LONG-TERM; MICROALBUMINURIA AB Purpose of review The results of recent clinical trials in early diabetic nephropathy demonstrate that current therapies designed to suppress microalbuminuria do not prevent renal function decline. However, recent observational studies refined the traditional model of early nephropathy in type 1 diabetes and may inform more effective therapies for the prevention of chronic kidney disease. Recent findings A contemporary model of early nephropathy in type 1 diabetes has emerged in which initiation of renal function decline occurs soon after the onset of microalbuminuria and is not conditional on progression to proteinuria. Early renal function decline can be diagnosed using serial measurement of serum cystatin C. Abnormal levels of markers of protein glycation, uric acid metabolism, and chronic inflammation appear to represent mechanisms unique to early renal function decline and distinct from those involved in microalbuminuria. Summary Recent findings refine the existing paradigm of early nephropathy in type 1 diabetes and have significant implications for research. Clinical tests - such as an algorithm for the serial determination of serum cystatin C - should be developed for monitoring early renal function decline for use as an outcome in clinical trials. C1 [Perkins, Bruce A.] Univ Toronto, Div Endocrinol & Metab, Toronto, ON M5G 2C4, Canada. [Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Krolewski, Andrzej S.] Harvard Univ, Sch Med, Boston, MA USA. RP Perkins, BA (reprint author), Univ Toronto, Div Endocrinol & Metab, 200 Elizabeth St,Room EN-12-217, Toronto, ON M5G 2C4, Canada. EM bruce.perkins@uhn.on.ca FU NIH [DK041526]; Canadian Diabetes Association; Banting and Best Diabetes Center FX This study was supported by NIH grant DK041526. B.A.P. is supported by new investigator awards for diabetes research from the Canadian Diabetes Association and the Banting and Best Diabetes Center. NR 50 TC 40 Z9 41 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAY PY 2009 VL 18 IS 3 BP 233 EP 240 DI 10.1097/MNH.0b013e3283293db1 PG 8 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 438MX UT WOS:000265560600008 PM 19300247 ER PT J AU Shirley, RM Baddley, JW AF Shirley, Rhett M. Baddley, John W. TI Cryptococcal lung disease SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Article DE amphotericin B; cryptococcosis; Cryptococcus neoformans; fluconazole; pneumonia ID ORGAN TRANSPLANT RECIPIENTS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; RECONSTITUTION INFLAMMATORY SYNDROME; BRONCHOALVEOLAR LAVAGE FLUID; VIRUS-NEGATIVE PATIENTS; PULMONARY CRYPTOCOCCOSIS; NEOFORMANS INFECTION; FUNGAL-INFECTIONS; HIV-INFECTION; CLINICAL MANIFESTATIONS AB Purpose of review Cryptococcosis is an important opportunistic fungal infection, especially in the immunocompromised patient. Meningitis is the most common manifestation of cryptococcosis; however, cryptococcal lung disease is probably underdiagnosed, and knowledge of epidemiology, diagnosis, and treatment is necessary. Recent findings Cryptococcal lung disease ranges from asymptomatic colonization or infection to severe pneumonia with respiratory failure. Clinical presentation of pulmonary cryptococcosis is highly variable and often is related to the immune status of the patient. There have been many important clinical trials outlining treatment of cryptococcal meningitis in patients with AIDS, but there is a lack of treatment data available for patients with cryptococcal lung disease. Treatment recommendations for cryptococcal lung disease are made on the basis of host immune status and severity of clinical illness. For less severe disease, fluconazole therapy is recommended. In immunocompromised patients, or those with severe disease, induction therapy with an amphotericin B preparation and flucytosine, followed by fluconazole as consolidation and maintenance therapy, is recommended. Summary Cryptococcal lung disease is an important and probably underdiagnosed infection. Knowledge of the epidemiology, diagnostic methodologies, and treatment is needed to ensure good patient outcomes. C1 [Shirley, Rhett M.; Baddley, John W.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Baddley, JW (reprint author), Univ Alabama, Dept Med, Div Infect Dis, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA. EM jbaddley@uab.edu FU Pfizer; Astellas Pharma; Merck and Co FX Dr Baddley has received research support from Pfizer, Astellas Pharma, and Merck and Co. NR 67 TC 18 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD MAY PY 2009 VL 15 IS 3 BP 254 EP 260 DI 10.1097/MCP.0b013e328329268d PG 7 WC Respiratory System SC Respiratory System GA 442XF UT WOS:000265873300011 PM 19352182 ER PT J AU Freedland, SJ Aronson, WJ AF Freedland, Stephen J. Aronson, William J. TI Dietary intervention strategies to modulate prostate cancer risk and prognosis SO CURRENT OPINION IN UROLOGY LA English DT Review DE carbohydrates; diet; fat; nutrition; prostate cancer ID GROWTH-FACTOR AXIS; LIFE-STYLE CHANGES; LOW-FAT DIET; BREAST-CANCER; MODIFICATION TRIAL; GENE-EXPRESSION; XENOGRAFTS; NUTRITION; ACIDS; RESTRICTION AB Purpose of review There is increasing interest in complementary and holistic approaches for cancer prevention and management. We sought to review the latest literature regarding dietary interventions for prostate cancer with a special emphasis on dietary fat and carbohydrate intake for modulating prognosis among men with prostate cancer. Recent findings Several recent prospective trials have investigated various dietary and lifestyle investigations on malignant prostate tissue biology. These interventions included a very low-fat (12% fat kcals) vegan diet with various supplements and lifestyle changes, a more traditional low-fat diet (25% fat kcals) with flaxseed supplementation, and a low-glycemic index diet. Low-glycemic index and very low-fat vegan diets (with supplements and lifestyle changes) alter tumor biology as assessed by tumor gene expression changes, with a common mechanism perhaps being weight loss whereas no effects were seen with a traditional low-fat diet. In mice, either very low-fat or low-carbohydrate diets significantly slow tumor growth independent of weight loss. Epidemiologic and preclinical data also suggest cholesterol intake and serum cholesterol levels may be linked with the development and progression of prostate cancer. Summary Small clinical trials suggest that tumor biology can be altered by either a vegan low-fat diet or eliminating simple carbohydrates accompanied by weight loss. Larger and longer term studies are needed to determine the clinical relevance of these findings. C1 [Freedland, Stephen J.] Duke Univ, Med Ctr, Dept Surg, Div Urol Surg,DPC,Sch Med, Durham, NC 27710 USA. [Freedland, Stephen J.] Duke Univ, Sch Med, Dept Pathol, Div Urol Surg, Durham, NC 27710 USA. [Freedland, Stephen J.] Durham VA Med Ctr, Urol Sect, Dept Surg, Durham, NC USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Surg, Urol Sect,Greater Los Angeles VA Med Ctr, Los Angeles, CA 90024 USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90024 USA. RP Freedland, SJ (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Urol Surg,DPC,Sch Med, Box 2626, Durham, NC 27710 USA. EM steve.freedland@duke.edu FU Department of Veterans Affairs; Department of Defense; AUA Foundation/Astellas Rising Star in Urology Award FX Supported by the Department of Veterans Affairs, Department of Defense, and the AUA Foundation/Astellas Rising Star in Urology Award. NR 32 TC 16 Z9 17 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0963-0643 J9 CURR OPIN UROL JI Curr. Opin. Urol. PD MAY PY 2009 VL 19 IS 3 BP 263 EP 267 DI 10.1097/MOU.0b013e328329ea6c PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 438XW UT WOS:000265590900008 PM 19300265 ER PT J AU Hoge, EA Brandstetter, K Moshier, S Pollack, MH Wong, KK Simon, NM AF Hoge, E. A. Brandstetter, K. Moshier, S. Pollack, M. H. Wong, K. K. Simon, N. M. TI BROAD SPECTRUM OF CYTOKINE ABNORMALITIES IN PANIC DISORDER AND POSTTRAUMATIC STRESS DISORDER SO DEPRESSION AND ANXIETY LA English DT Article DE cytokine; inflammation; proinflammatory; chemokine; posttraumatic stress disorder; panic; PTSD; stress ID CORONARY-HEART-DISEASE; PSYCHOLOGICAL STRESS; MAJOR DEPRESSION; SOLUBLE INTERLEUKIN-2; SERUM INTERLEUKIN-2; PSYCHOSOCIAL STRESS; ALLOSTATIC LOAD; SEX-DIFFERENCES; ADIPOSE-TISSUE; IMMUNE-SYSTEM AB Background: Proinflammatory cytokines have been reported to be elevated in individuals experiencing chronic stress as well as in those with major depressive disorde. Much less is known about cytokines in anxiety disorders such as Posttraumatic stress disorder (PTSD) and Panic disorder (PD). We hypothesized that PD and PTSD would be associated with a generalized proinflammatory cytokine signature. Method: We utilized Luminex technology to examine 20 cytokines and chemokines in serum from 48 well-characterized individuals with a primary DSM-IV PD or PTSD diagnosis, and 48 age- and gender-matched healthy controls. We conservatively employed a Bonferroni correction for multiple testing (alpha=.05/20 =.0025). Results: Individuals with primary PTSD or PD had significantly elevated median peripheral cytokine levels for 18 of 20 different cytokines compared to age- and gender-matched healthy controls (all P <. 0025). To assess for the presence of a generalized proinflammatory state, we also examined the proportion of subjects with detectable levels of at least six of nine common proinflammatory cytokines and chemokines (IL-6, IL-1 alpha, IL-1 beta, IL-8, MCP-1, MIP-1 alpha, Eotaxin, GM-CSF, and IFN-alpha). For men and women, 87% of anxiety patients had six or more detectable levels of these proinflammatory cytokines, compared with only 25% of controls (Fisher's Exact Test (FET) P=.000). Confirmatory analysis of the subset of individuals without current psychiatric mediacation use or comorbid depression was of comparable significance. Conclusions: These findings suggest that a generalized inflammatory state may be present in individuals with PD or PTSD. Depression and Anxiety 26:447-455, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Simon, N. M.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Boston, MA 02114 USA. [Brandstetter, K.; Wong, K. K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM nsimon@partners.org RI Hoge, Elizabeth/H-5879-2012 OI Hoge, Elizabeth/0000-0002-5513-2292 FU Highland Street Foundation FX This study was supported in part by the Highland Street Foundation. NR 61 TC 121 Z9 123 U1 2 U2 24 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD MAY PY 2009 VL 26 IS 5 BP 447 EP 455 DI 10.1002/da.20564 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 442XP UT WOS:000265874300008 PM 19319993 ER PT J AU Tierney, E Barker, A Ahdout, J Hanke, CW Moy, RL Kouba, DJ AF Tierney, Emily Barker, Allison Ahdout, Jennifer Hanke, C. William Moy, Ronald L. Kouba, David J. TI Photodynamic Therapy for the Treatment of Cutaneous Neoplasia, Inflammatory Disorders, and Photoaging SO DERMATOLOGIC SURGERY LA English DT Review ID BASAL-CELL CARCINOMA; DELTA-AMINOLEVULINIC-ACID; TOPICAL METHYL AMINOLEVULINATE; NONMELANOMA SKIN-CANCER; INTENSE PULSED-LIGHT; RENAL-TRANSPLANT RECIPIENTS; MULTIPLE ACTINIC KERATOSES; TERM-FOLLOW-UP; 5-AMINOLEVULINIC ACID; BOWENS-DISEASE AB Photodynamic therapy (PDT) has demonstrated high efficacy, minimal side effects, and improved cosmetic outcome when used for the treatment of actinic keratoses (AK), basal cell carcinoma (BCC), squamous cell carcinoma, and photoaging. To review the literature on the use of PDT in dermatologic surgery using MEDLINE. Published clinical studies using PDT in the treatment of AKs yield overall efficacy rates ranging from 50% to 71% with one treatment to as high as 88% to 90% with two or more treatments. For superficial BCC, initial clearance rates were 76% to 97%, and for Bowen's disease, initial clearance rates ranged from 72% to 94% overall. The use of PDT for photorejuvenation is a relatively new application of this technology, which has shown promise in improving the appearance of fine lines, pigmentary variation, and telangiectasias. The advantages of photodynamic therapy include the capacity for noninvasive targeted therapy through topical application of aminolevulinic acid and methyl aminolevulinic acid, with outstanding cosmetic results. Although the theory behind the use of chemical photosensitizers and ultraviolet light to treat a wide variety of skin disorders is straightforward, the practical application of this technology is evolving. Additional research into the precise mechanisms of action for specific photosensitizers and optimal light sources will be highly beneficial to the advancement of this technology. The authors have indicated no significant interest with commercial supporters. C1 [Kouba, David J.] Henry Ford Hlth Syst, Detroit, MI USA. [Tierney, Emily; Hanke, C. William] Laser & Skin Surg Ctr Indiana, Dept Dermatol, Indiana, PA USA. [Barker, Allison] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Ahdout, Jennifer; Moy, Ronald L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Moy, Ronald L.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Kouba, DJ (reprint author), Henry Ford Hlth Syst Dermatol, 3031 W Grand Blvd,Suite 800, Detroit, MI 48202 USA. EM dkouba1@hfhs.org NR 93 TC 36 Z9 40 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAY PY 2009 VL 35 IS 5 BP 725 EP 746 DI 10.1111/j.1524-4725.2009.01117.x PG 22 WC Dermatology; Surgery SC Dermatology; Surgery GA 437IV UT WOS:000265481500001 PM 19309338 ER PT J AU Gori, F Zhu, ED Demay, MB AF Gori, Francesca Zhu, Eric D. Demay, Marie B. TI Perichondrial expression of Wdr5 regulates chondrocyte proliferation and differentiation SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Wdr5; FGF18; Twist-1; Chondrogenesis ID ENDOCHONDRAL BONE-DEVELOPMENT; HORMONE-RELATED PEPTIDE; CHICK LIMB DEVELOPMENT; WD-40 REPEAT PROTEIN; INDIAN-HEDGEHOG; OSTEOBLAST DIFFERENTIATION; PARATHYROID-HORMONE; GROWTH-PLATE; MORPHOGENETIC PROTEINS; CELL-PROLIFERATION AB Wdr5 is developmentally expressed in osteoblasts and is required for osteoblast differentiation. Mice overexpressing Wdr5 under the control of the mouse alpha(1)I collagen promoter (Col I-Wdr5) display accelerated osteoblast differentiation as well as accelerated chondrocyte differentiation, suggesting that overexpression of Wdr5 in osteoblasts affects chondrocyte differentiation. To elucidate the molecular mechanism by which overexpression of Wdr5 in the perichondrium regulates chondrocyte differentiation, studies were undertaken using skeletal elements and cultured metatarsals isolated from wild-type and Col I-Wdr5 embryos. FGF18 mRNA levels were decreased in Col I-Wdr5 humeri. Furthermore, local delivery of FGF18 to the bone collar of ex vivo cultures of metatarsals attenuated the chondrocyte phenotype of the Col I-Wdr5 metatarsals. Impairing local FGF action in wild-type metatarsals resulted in a chondrocyte phenotype analogous to that of Col I-Wdr5 metatarsals implicating impaired FGF action as the cause of the phenotype observed. The expression of Twist-1, which regulates chondrocyte differentiation, was increased in Col I-Wdr5 humeri. Chromatin immunoprecipitation analyses demonstrated that Wdr5 is recruited to the Twist-1 promoter. These findings support a model in which overexpression of Wdr5 in the perichondrium promotes chondrocyte differentiation by modulating the expression of Twist-1 and FGF18. (C) 2009 Elsevier Inc. All rights reserved. C1 [Gori, Francesca; Zhu, Eric D.; Demay, Marie B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Gori, F (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM gori@helix.mgh.harvard.edu FU National Institutes of Health [DK36597] FX This work was supported by Grant DK36597 (MD) from the National Institutes of Health. NR 54 TC 6 Z9 7 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 1 PY 2009 VL 329 IS 1 BP 36 EP 43 DI 10.1016/j.ydbio.2009.02.006 PG 8 WC Developmental Biology SC Developmental Biology GA 437XI UT WOS:000265519800004 PM 19217897 ER PT J AU Isganaitis, E Jimenez-Chillaron, J Woo, M Chow, A DeCoste, J Vokes, M Liu, MW Kasif, S Zavacki, AM Leshan, RL Myers, MG Patti, ME AF Isganaitis, Elvira Jimenez-Chillaron, Jose Woo, Melissa Chow, Alice DeCoste, Jennifer Vokes, Martha Liu, Manway Kasif, Simon Zavacki, Ann-Marie Leshan, Rebecca L. Myers, Martin G. Patti, Mary-Elizabeth TI Accelerated Postnatal Growth Increases Lipogenic Gene Expression and Adipocyte Size in Low-Birth Weight Mice SO DIABETES LA English DT Article ID FOR-GESTATIONAL-AGE; CATCH-UP GROWTH; WHITE ADIPOSE-TISSUE; INSULIN-RESISTANCE; CELL-SIZE; IN-UTERO; OBESITY; MITOCHONDRIAL; RAT; CHILDREN AB OBJECTIVE-To characterize the hormonal milieu and adipose gene expression in response to catch-up growth (CUG), a growth pattern associated with obesity and diabetes risk, in a mouse model of low birth weight (LBW). RESEARCH DESIGN AND METHODS-ICR mice were food restricted by 50% from gestational days 12.5-18.5, reducing offspring birth weight by 25%. During the suckling period, dams were either fed ad libitum, permitting CUG in offspring, or food restricted, preventing CUG. Offspring were killed at age 3 weeks, and gonadal fat was removed for RNA extraction, array analysis, RT-PCR, and evaluation of cell size and number. Serum insulin, thyroxine (T4), corticosterone, and adipokines were measured. RESULTS-At age 3 weeks, LBW mice with CUG (designated U-C) had body weight comparable with controls (designated C-C) weight was reduced by 49% in LBW mice without CUG (designated U-U). Adiposity was altered by postnatal nutrition, with gonadal fat increased by 50% in U-C and decreased by 58% in U-U mice (P < 0.05 vs. C-C mice). Adipose expression of the lipogenic genes Fasn, AccI, Lpin1, and Srebf1 was significantly increased in U-C compared with both C-C and U-U mice (P < 0.05). Mitochondrial DNA copy number was reduced by > 50% in U-C versus U-U mice (P = 0.014). Although cell numbers did not differ, mean adipocyte diameter was increased in U-C and reduced in U-U mice (P < 0.01). CONCLUSIONS-CUG results in increased adipose tissue lipogenic gene expression and adipocyte diameter but not increased cellularity, suggesting that catch-up fat is primarily associated with lipogenesis rather than adipogenesis in this murine model. Diabetes 58:1192-1200, 2009 C1 [Isganaitis, Elvira; Woo, Melissa; Chow, Alice; DeCoste, Jennifer; Vokes, Martha; Patti, Mary-Elizabeth] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Jimenez-Chillaron, Jose] Univ Barcelona, Hosp Sant Joan de Deu, Barcelona, Spain. [Liu, Manway] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Kasif, Simon] Boston Univ, Ctr Adv Genom Technol, Boston, MA 02215 USA. [Zavacki, Ann-Marie] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Leshan, Rebecca L.; Myers, Martin G.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. RP Patti, ME (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM mary.elizabeth.patti@joslin.harvard.edu FU American Diabetes Association; Endocrine Fellows Foundation; Human Growth Foundation; Lawson-Wilkins Pediatric Endocrine Society [DK57768]; American Heart Association Predoctoral Fellowship; [DK98059] FX We acknowledge support from DK98059 and the American Diabetes Association (both to M.-E.P.); the Endocrine Fellows Foundation, the Human Growth Foundation, and the Lawson-Wilkins Pediatric Endocrine Society (to E.I.); DK57768 (to M.G.M.); and an American Heart Association Predoctoral Fellowship (to R.L.L.). NR 50 TC 44 Z9 47 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2009 VL 58 IS 5 BP 1192 EP 1200 DI 10.2337/db08-1266 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 440YX UT WOS:000265736700019 PM 19208909 ER PT J AU Eid, AA Gorin, Y Fagg, BM Maalouf, R Barnes, JL Block, K Abboud, HE AF Eid, Assaad A. Gorin, Yves Fagg, Bridget M. Maalouf, Rita Barnes, Jeffrey L. Block, Karen Abboud, Hanna E. TI Mechanisms of Podocyte Injury in Diabetes Role of Cytochrome P450 and NADPH Oxidases SO DIABETES LA English DT Article ID 20-HYDROXYEICOSATETRAENOIC ACID; ARACHIDONIC-ACID; EPITHELIAL-CELLS; RAT-KIDNEY; NEPHROPATHY; APOPTOSIS; GLUCOSE; MICE; NUMBER; CYTOTOXICITY AB OBJECTIVE-We investigated the role of cytochrome P450 of the 4A family (CYP4A), its metabolites, and NADPH oxidases both in reactive oxygen species (ROS) production and apoptosis of podocytes exposed to high glucose and in OVE26 mice, a model of type 1 diabetes. RESEARCH DESIGN AND METHODS-Apoptosis, albuminuria, ROS generation, NADPH superoxide generation, CYP4A and Nox protein expression, and mRNA levels were measured in vitro and in vivo. RESULTS-Exposure of mouse podocytes to high glucose resulted in apoptosis, with approximately one-third of the cells being apoptotic by 72 h. High-glucose treatment increased ROS generation and was associated with sequential upregulation of CYP4A and an increase in 20-hydroxyeicosatetraenoic acid (20-HETE) and Nox oxidases. This is consistent with the observation of delayed induction of NADPH oxidase activity by high glucose. The effects of high glucose on NADPH oxidase activity, Nox proteins and mRNA expression, and apoptosis were blocked by N-hydroxy-N'-(4-butyl-2-methylphenol) formamidine (HET0016), an inhibitor of CYP4A, and were mimicked by 20-HETE. CYP4A and Nox oxidase expression was upregulated in glomeruli of type I diabetic OVE26 mice. Treatment of OVE26 mice with HET0016 decreased NADPH oxidase activity and Nox1 and Nox4 protein expression and ameliorated apoptosis and albuminuria. CONCLUSIONS-Generation of ROS by CYP4A monooxygenases, 20-HETE, and Nox oxidases is involved in podocyte apoptosis in vitro and in vivo. Inhibition of selected cytochrome P450 isoforms prevented podocyte apoptosis and reduced proteinuria in diabetes. Diabetes 58:1201-1211, 2009 C1 [Eid, Assaad A.; Gorin, Yves; Fagg, Bridget M.; Maalouf, Rita; Barnes, Jeffrey L.; Block, Karen; Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Barnes, Jeffrey L.; Block, Karen; Abboud, Hanna E.] S Texas Vet Healthcare Syst, San Antonio, TX USA. RP Abboud, HE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM abboud@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925 FU National Kidney Foundation Postdoctoral Fellowship; American Heart Association South Central Affiliate; Juvenile Diabetes Research Foundation; National Institutes of Health [K01DK-076923, DK061597, DK-R01-078971]; American Diabetes Association FX Support for these studies was provided by the following sources: a National Kidney Foundation Postdoctoral Fellowship (to A.A.E.), an American Heart Association South Central Affiliate and Juvenile Diabetes Research Foundation regular research grant (to Y.G.), National Institutes of Health Grant K01DK-076923 (to K.B.), National Institutes of Health, George O'Brien Kidney Center-morphology core grant no. DK061597 (to J.L.B.), and National Institutes of Health Grant DK-R01-078971 and grants from the American Diabetes Association and the Juvenile Diabetes Research Foundation (to H.E.A.). NR 42 TC 124 Z9 132 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2009 VL 58 IS 5 BP 1201 EP 1211 DI 10.2337/db08-1536 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 440YX UT WOS:000265736700020 PM 19208908 ER PT J AU McGrady, ME Laffel, L Drotar, D Repaske, D Hood, KK AF McGrady, Meghan E. Laffel, Lori Drotar, Dennis Repaske, David Hood, Korey K. TI Depressive Symptoms and Glycemic Control in Adolescents With Type 1 Diabetes Mediational role of blood glucose monitoring SO DIABETES CARE LA English DT Article ID CHILDREN; ADHERENCE AB OBJECTIVE - To determine whether the association between depressive symptoms and glycemic control is mediated by blood glucose monitoring (BGM). RESEARCH DESIGN AND METHODS - A total of 276 adolescents with type 1 diabetes (mean age +/ SD, 15.6 +/- 1.4 years) completed a measure of depressive symptoms. Socio-demographic and family characteristics were obtained from caregivers. BGM frequency and glycemic control were obtained at a clinic Visit. RESULTS - Separate regression analyses revealed that depressive symptoms were associated with lower BGM frequency (B = -0.03; P = 0.04) and higher A1C (B = 0.03; P = 0.05) and that lower BGM frequency was associated With higher A1C (B = -0.39; P < 0.001). With depressive symptoms and BGM frequency included together, only BGM frequency was associated with A1C and depressive symptoms became nonsignificant (B = 0.02; P = 0.19). The Sobel test was significant (Z = 1.96; P < 0.05) and showed that 38% of the depression-A1C link can be explained by BGM. CONCLUSIONS - BGM is a mediator between depressive symptoms and glycemic control in adolescents with type 1 diabetes. C1 [McGrady, Meghan E.; Drotar, Dennis; Hood, Korey K.] Cincinnati Childrens Hosp Med Ctr, Ctr Treatment Adherence, Div Behav Med & Clin Psychol, Cincinnati, OH USA. [Repaske, David] Cincinnati Childrens Hosp Med Ctr, Ctr Diabet, Div Endocrinol, Cincinnati, OH USA. [McGrady, Meghan E.] Univ Cincinnati, Dept Psychol, Cincinnati, OH 45221 USA. [Drotar, Dennis; Repaske, David; Hood, Korey K.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45221 USA. [Laffel, Lori] Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect,Genet & Epid, Boston, MA 02115 USA. RP Hood, KK (reprint author), Cincinnati Childrens Hosp Med Ctr, Ctr Treatment Adherence, Div Behav Med & Clin Psychol, Cincinnati, OH USA. EM korey.hood@cchmc.org FU National Institute of Diabetes and Digestive and Kidney Diseases FX No potential conflicts of interest relevant to this article were reported. NR 15 TC 52 Z9 53 U1 2 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2009 VL 32 IS 5 BP 804 EP 806 DI 10.2337/dc08-2111 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444EG UT WOS:000265962800010 PM 19228870 ER PT J AU Ficociello, LH Perkins, BA Roshan, B Weinberg, JM Aschengrau, A Warram, JH Krolewski, AS AF Ficociello, Linda H. Perkins, Bruce A. Roshan, Bijan Weinberg, Janice M. Aschengrau, Ann Warram, James H. Krolewski, Andrzej S. TI Renal Hyperfiltration and the Development of Microalbuminuria in Type 1 Diabetes SO DIABETES CARE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; INSULIN-DEPENDENT DIABETICS; CREATININE-BASED METHODS; ALBUMIN EXCRETION RATE; CYSTATIN-C; KIDNEY-DISEASE; PROGRESSIVE NATURE; LATE NEPHROPATHY; RISK; PREDICTION AB OBJECTIVE- The purpose of this study was to examine prospectively whether renal hyperfiltration is associated with the development of microalbuminuria in patients With type I diabetes, after taking into account known risk factors. RESEARCH DESIGN AND METHODS- The study group comprised 426 participants with normoalbuminuria from the First Joslin Kidney Study, followed for 15 years. Glomerular filtration rate was estimated by serum cystatin C, and hyperfiltration was defined as exceeding the 97.5th percentile of the sex-specific distribution of a similarly aged, nondiabetic population 2 for men and women, respectively). The outcome was time to (134 and 149 ml/min per 1.73 m(2) for men and women, respectively). The outcome was time to microalbuminuria development (multiple albumin excretion rate >30 mu g/min). Hazard ratios (HRs) for microalbuminuria were calculated at 5, 10, and 15 years. RESULTS- Renal hyperfiltrabon was present in 24% Of the Study group and did not increase the risk of developing microalbuminuria. The unadjusted HR for microalbuminuria comparing those With and without hyperfiltration at baseline was 0.8 (95% Cl 0.4-1.7) during the first 5 years, 1.0 (0.6-1.7) during the first 10 years, and 0.8 (0.5-1.4) during 15 years of follow-up. The model adjusted for baseline known risk factors including A1C, age at diagnosis of diabetes, diabetes duration, and cigarette smoking resulted in similar HRS. In addition, incorporating changes in hyperfiltration status during follow-up had minimal impact on the HRs for microalbuminuria. CONCLUSIONS- Renal hyperfiltration does not have an impact on the development of microalburninuria in type 1 diabetes during 5, 10, or 15 years of follow-up. C1 [Ficociello, Linda H.; Roshan, Bijan; Warram, James H.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Ficociello, Linda H.; Weinberg, Janice M.; Aschengrau, Ann] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Perkins, Bruce A.] Toronto Gen Hosp, Dept Endocrinol & Metab, Toronto, ON, Canada. [Roshan, Bijan; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Boston, MA USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu OI Aschengrau, Ann/0000-0001-8153-7712 FU National Institutes of Health [041526] FX This research was supported by National Institutes of Health Grant DK 041526. NR 23 TC 39 Z9 40 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2009 VL 32 IS 5 BP 889 EP 893 DI 10.2337/dc08-1560 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444EG UT WOS:000265962800028 PM 19196883 ER PT J AU Jain, SH Massaro, JM Hoffmann, U Rosito, GA Vasan, RS Raji, A O'Donnell, CJ Meigs, JB Fox, CS AF Jain, Shilpa H. Massaro, Joseph M. Hoffmann, Udo Rosito, Guido A. Vasan, Ramachandran S. Raji, Annaswamy O'Donnell, Christopher J. Meigs, James B. Fox, Caroline S. TI Cross-Sectional Associations Between Abdominal and Thoracic Adipose Tissue Compartments and Adiponectin and Resistin in the Framingham Heart Study SO DIABETES CARE LA English DT Article; Proceedings Paper CT 68th Annual Meeting of the American-Diabetes-Association CY JUN 06-10, 2008 CL San Francisco, CA SP Amer Diabet Assoc ID BODY-FAT DISTRIBUTION; RISK-FACTORS; INSULIN SENSITIVITY; VISCERAL ADIPOSITY; GENE-EXPRESSION; METABOLIC RISK; OLDER-ADULTS; OBESITY; ADIPOCYTOKINES; CALCIFICATION AB OBJECTIVE- To test the association of regional fat depots with circulating adiponectin and resistin concentrations and to assess the potential mediating effect of adipokines on associations between abdominal fat depots and cardiometabolic risk factors. RESEARCH DESIGN AND METHODS- Participants from the Framingham Heart Study offspring cohort (n = 916, 55% women; mean age 59 years) free of cardiovascular disease underwent computed tomography measurement of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), pericardial fat, and intrathoracic fat, volumes and assays of circulating adiponectin and resistin. RESULTS- VAT, SAT, pericardial fat, and intrathoracic fat were negatively correlated with adiponectin (r = -0.19 to -0.34, P < 0.001 [women]; r = -0.15 to -0.26, P < 0.01 [men] except SAT) and positively correlated with resistin (r = 0.16-0.21, P < 0.001 [women]; r = 0.11-0.14, P < 0.05 [men] except VAT). VAT increased the multivariable model R(2) for adiponectin from 2-4% to 10-13% and for resistin from 3-4% to 3-6%. Adjustment for adipokines did not fully attenuate associations between VAT, SAT, and cardiometabolic risk factors. CONCLUSIONS- Adiponectin and resistin are correlated with fat depots cross-sectionally, but none of the adipokines can serve as surrogates for the fat depots. Relations between VAT SAT, and cardiometabolic risk factors were not fully explained by adiponectin or resistin concentrations. C1 [Jain, Shilpa H.; Raji, Annaswamy; Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Hoffmann, Udo; Rosito, Guido A.] Massachusetts Gen Hosp, Div Radiol, Boston, MA 02114 USA. [Rosito, Guido A.] Fed Fdn Sch Med Sci Porto Alegre, Porto Alegre, RS, Brazil. [Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Fox, CS (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 75 Francis St, Boston, MA 02115 USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU NCRR NIH HHS [M01 RR001066, M01-RR-01066]; NHLBI NIH HHS [N01HC25195, 2K24HL04334, K24 HL004334, N01-HC-25195, T32 HL007609]; NIDDK NIH HHS [K24 DK080140, R01 DK080739] NR 22 TC 27 Z9 28 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2009 VL 32 IS 5 BP 903 EP 908 DI 10.2337/dc08-1733 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444EG UT WOS:000265962800032 PM 19223612 ER PT J AU Palmer, JP AF Palmer, Jerry P. TI C-peptide in the natural history of type 1 diabetes SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Review ID BETA-CELL FUNCTION; ANTI-CD3 MONOCLONAL-ANTIBODY; INSULIN-SECRETION; BLOOD-FLOW; ONSET; TRIAL; DYSFUNCTION; MELLITUS; GLUCOSE; ASSOCIATION AB Type 1 diabetes is diagnosed when the patient's endogenous insulin secretion decreases to a level which results in hyperglycemia. After diagnosis, insulin secretion continues to decline. As a reference for clinical trials trying to preserve endogenous beta-cell function in patients with recently diagnosed type 1 diabetes, in this short review I attempt to Summarize the natural history of endogenous beta-cell function after the diagnosis of type 1 diabetes. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Palmer, Jerry P.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Palmer, Jerry P.] Univ Washington, Seattle, WA 98195 USA. RP Palmer, JP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. EM jpp@u.washington.edu FU NIH [DK62203, DK17047, DK60155]; Medical Research Service of the Department of Veteran Affairs FX The author receives support from the following NIH grants: DK62203, DK17047, DK60155 and thanks Meron Rezene for helping in preparing this manuscript. Supported (in part) by the Medical Research Service of the Department of Veteran Affairs. NR 29 TC 22 Z9 23 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1520-7560 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD MAY PY 2009 VL 25 IS 4 BP 325 EP 328 DI 10.1002/dmrr.943 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 449RH UT WOS:000266347200006 PM 19267337 ER PT J AU Abudayyeh, S Hoffman, J El-Zimaity, HT Graham, DY AF Abudayyeh, S. Hoffman, J. El-Zimaity, H. T. Graham, D. Y. TI Prospective, randomized, pathologist-blinded study of disposable alligator-jaw biopsy forceps for gastric mucosal biopsy SO DIGESTIVE AND LIVER DISEASE LA English DT Article DE Adequacy; Depth; Endoscopy; Forceps; Gastric biopsy ID ENDOSCOPIC BIOPSY; GASTROINTESTINAL ENDOSCOPY; SPECIMENS; ADEQUACY; PERFORMANCE; SYSTEM; NEEDLE AB Background. Endoscopic biopsy forceps differ in the size and shape of the biopsy cup and the presence or absence of a needle. Methods. We compared four different "large cup" forceps (three with needles) designed for 2.8 min biopsy channels. A gastric antral and corpus biopsy were obtained with each. Parameters examined included: weight (mg), length (mm), orientation (poor, good), intactness (1, 2, or 3 pieces), depth (superficial, above muscularis mucosae, included muscularis mucosae), crush artefact (yes, no), and overall adequacy (inadequate, suboptimal, adequate). Results. Twenty-four patients were enrolled (191 biopsies). The median length was approximately 5 mm (range 1.1-8.2 mm). Histologically inadequate specimens were present in 4% with the forceps without needle compared to 16% of those with needles (P = 0.061) and there were significantly fewer specimens in three or more pieces than did the forceps with needles 2.1% vs. 12.6% (P<0.05). Conclusions. Current alligator style forceps provide a high proportion of acceptable specimens with only minor differences between brands. Forceps from one source were least preferred by endoscopy assistants and had the highest rates of inadequate biopsies and biopsies with crush artefact. Forceps without needles provide histologically acceptable samples slightly more frequently than those with needles. (C) 2008 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. C1 [Graham, D. Y.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, RM 3A-320 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu FU Office of Research and Development Medical Research Service Department of Veterans Affairs; Public Health Service [DK56338]; Texas Gulf Coast Digestive Diseases Center FX This was an investigator imitated project and was supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs and by Public Health Service grant DK56338 which funds the Texas Gulf Coast Digestive Diseases Center. NR 15 TC 5 Z9 5 U1 0 U2 0 PU PACINI EDITORE PI PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD MAY PY 2009 VL 41 IS 5 BP 340 EP 344 DI 10.1016/j.dld.2008.07.317 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 449SI UT WOS:000266349900004 PM 18799373 ER PT J AU Peura, DA Freston, JW Haber, MM Kovacs, TO Hunt, B Atkinson, S AF Peura, David A. Freston, James W. Haber, Marian M. Kovacs, Thomas O. Hunt, Barbara Atkinson, Stuart TI Lansoprazole for Long-Term Maintenance Therapy of Erosive Esophagitis: Double-Blind Comparison with Ranitidine SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Erosive esophagitis; Gastroesophageal reflux disease; Maintenance therapy; Lansoprazole; Heartburn; Ranitidine ID GASTROESOPHAGEAL-REFLUX DISEASE; QUALITY-OF-LIFE; NATURAL-HISTORY; DOSE LANSOPRAZOLE; OMEPRAZOLE; ESOMEPRAZOLE; PANTOPRAZOLE; RELAPSE; TRIAL; MULTICENTER AB In a study evaluating the efficacy and safety of lansoprazole to prevent the relapse of erosive esophagitis (EE), 206 of 241 patients (85%) healed after open-label treatment with lansoprazole 30 mg once daily for 8 weeks and received double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily for up to 1 year. At 1 year, 67% of lansoprazole-treated and 13% of ranitidine-treated patients remained healed (P < 0.001). Lansoprazole-treated patients experienced significantly greater symptom relief (P < 0.001), and, if asymptomatic at entry into the maintenance phase, remained asymptomatic for significantly longer than ranitidine-treated patients (P < 0.001). Symptom status correlated with healing (P = 0.001), supporting the symptom-directed management of EE. Both treatments were well tolerated and no unexpected events occurred. Daily therapy with lansoprazole to prevent the relapse of EE is effective, well tolerated, and superior to ranitidine in the maintenance of healing and symptom relief. C1 [Peura, David A.] Univ Virginia Hlth Syst, Charlottesville, VA 22908 USA. [Freston, James W.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Haber, Marian M.] Drexel Univ, Coll Med, Dept Pathol, Philadelphia, PA 19104 USA. [Kovacs, Thomas O.] CURE Clin, VA Greater Healthcare Syst, Los Angeles, CA USA. [Hunt, Barbara; Atkinson, Stuart] Takeda Global Res & Dev Ctr Inc, Deerfield, IL USA. RP Peura, DA (reprint author), Univ Virginia Hlth Syst, Charlottesville, VA 22908 USA. EM dap8v@virginia.edu FU Takeda Global Research & Development Center, Inc., Deerfield, IL, USA [M94-140] FX This study (M94-140) was funded by Takeda Global Research & Development Center, Inc., Deerfield, IL, USA (TAP Pharmaceutical Products Inc. is now part of Takeda Global Research & Development Center, Inc.). Editorial support for the preparation of this article was provided by Rx Communications (UK). Dr. Peura is a consultant for Takeda Global Research & Development Center, Inc., and is a member of the speaker's bureau for Takeda Pharmaceuticals North America, Inc., Astra Zeneca, and Santarus. Dr. Freston serves as a consultant for Takeda Global Research & Development Center, Inc., Takeda Pharmaceuticals North America, Inc., GlaxoSmithKline, and EnteroMedics Inc. Dr. Haber is a consultant for Takeda Global Research & Development Center, Inc. Dr. Kovacs confirms that he has no conflicts of interest or disclosures. NR 36 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2009 VL 54 IS 5 BP 955 EP 963 DI 10.1007/s10620-008-0466-9 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 427WP UT WOS:000264810100006 PM 18726153 ER PT J AU Pisegna, JR Karlstadt, RG Norton, JA Fogel, R Oh, DS Graepel, GJ Dorr, MB AF Pisegna, Joseph R. Karlstadt, Robyn G. Norton, Jeffrey A. Fogel, Ronald Oh, David S. Graepel, G. Jay Dorr, Mary Beth TI Effect of Preoperative Intravenous Pantoprazole in Elective-Surgery Patients: A Pilot Study SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Intravenous; Pantoprazole; Aspiration pneumonia; Gastric volume; Gastric acid output ID EMERGENCY CESAREAN-SECTION; GASTRIC-ACID HYPERSECRETION; ZOLLINGER-ELLISON-SYNDROME; PULMONARY ASPIRATION; GENERAL-ANESTHESIA; ORAL RANITIDINE; FLUID PROPERTY; OMEPRAZOLE; PH; VOLUME AB Background This study evaluated the effects of intravenous pantoprazole on gastric volume and acid output in elective-surgical patients. Methods This is a multicenter, randomized, pilot study of adult patients receiving intravenous pantoprazole: 40 mg every 24 h, 40 mg every 12 h (q12h) or 80 mg q12h. The first dose was administered 1 h before general anesthesia for surgery. All gastric fluid was aspirated through a nasogastric tube 1 h before dosing and through the postoperative period. Aspirate volume was recorded; pH and H(+) concentrations were measured. Result Twenty-six patients were enrolled and 21 were evaluable. Pantoprazole was well tolerated. All regimens decreased gastric acid output and volume, and increased pH within 1 h of dosing. Effects were sustained for up to 12 h following single-dose administration. Conclusions Intravenous pantoprazole administered prior to anesthesia induction may be efficacious for the reduction of gastric volume and acid output, and for pulmonary aspiration prophylaxis in surgical patients. C1 [Pisegna, Joseph R.; Oh, David S.] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Pisegna, Joseph R.; Oh, David S.] VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol 691 111C, Los Angeles, CA 90073 USA. [Pisegna, Joseph R.; Oh, David S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Karlstadt, Robyn G.; Graepel, G. Jay; Dorr, Mary Beth] Wyeth Pharmaceut, Global Med Affairs, Collegeville, PA USA. [Norton, Jeffrey A.] Stanford Univ, Dept Surg, Sch Med, San Francisco, CA USA. [Fogel, Ronald] Henry Ford Hlth Syst, Div Gastroenterol, Detroit, MI USA. RP Pisegna, JR (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol 691 111C, Los Angeles, CA 90073 USA. EM jpisegna@ucla.edu FU Wyeth Pharmaceuticals, Collegeville, PA; Wyeth; Novartis FX This study was funded by Wyeth Pharmaceuticals, Collegeville, PA. Conflicts-of-interest: Dr. David Oh-grant support from Wyeth; Dr. Joseph Pisegna-consultant, Grant Support from and Speaker for: Wyeth, Astra Zeneca, Takeda (TAP) and Novartis; Dr. Jeffrey Norton-none to disclose; Dr. Ronald Fogel-none to disclose; Jay Graepel and Mary Beth Dorr are currently and Robyn Karlstadt was formerly employed by Wyeth Pharmaceuticals. NR 27 TC 3 Z9 4 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2009 VL 54 IS 5 BP 1041 EP 1049 DI 10.1007/s10620-008-0445-1 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 427WP UT WOS:000264810100018 PM 18754096 ER PT J AU Huang, PL AF Huang, Paul L. TI A comprehensive definition for metabolic syndrome SO DISEASE MODELS & MECHANISMS LA English DT Article ID INSULIN-RESISTANCE; ENDOTHELIAL DYSFUNCTION; PROVISIONAL REPORT; DIAGNOSIS; CONSULTATION; OBESITY; AKT AB The metabolic syndrome refers to the co-occurrence of several known cardiovascular risk factors, including insulin resistance obesity, atherogenic dyslipidemia and hypertension. These conditions are interrelated and share underlying mediators, mechanisms and pathways. There has been recent controversy about, its definition and its utility. In this article, I review the current definitions for the metabolic syndrome and why the concept is important. It identifies a subgroup of patients with shared pathophysiology who are at high risk of developing cardiovascular disease and type 2 diabetes. By considering the central features of the metabolic syndrome and how they are related, we may better understand the underlying pathophysiology and disease pathogenesis. A comprehensive definition for the metabolic syndrome and its key features would facilitate research into its causes and hopefully lead to new insights into pharmacologic and lifestyle treatment approaches. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM phuang1@partners.org FU NINDS NIH HHS [R01 NS033335] NR 20 TC 182 Z9 193 U1 8 U2 21 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD MAY-JUN PY 2009 VL 2 IS 5-6 BP 231 EP 237 DI 10.1242/dmm.001180 PG 11 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 476PS UT WOS:000268455300009 PM 19407331 ER PT J AU Batki, SL Canfield, KM Smyth, E Ploutz-Snyder, R AF Batki, Steven L. Canfield, Kelly M. Smyth, Emily Ploutz-Snyder, Robert TI Health-related quality of life in methadone maintenance patients with untreated hepatitis C virus infection SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Hepatitis C; Methadone; Opioid; Substance abuse; Quality of life; Health; Psychiatry ID INJECTION-DRUG USERS; RISK-FACTORS; SURVEY QUESTIONNAIRE; HCV-INFECTION; PREVALENCE; DEPRESSION; INTERFERON-ALPHA-2B; MANAGEMENT; REDUCTION; EQUIPMENT AB Objective: To assess health-related quality of life (HRQOL) in methadone maintenance treatment (MMT) patients with untreated chronic HCV infection and to determine the clinical factors that predict HRQOL. Method: HRQOL was measured in 100 MMT patients entering an HCV treatment trial. Subjects were mostly male (61%) and white (81%) with a mean age of 43 (+/- 10). 57% had a current non-substance use psychiatric disorder. 55% had a current (past 12 months) substance use disorder, including 44% with current opioid or cocaine abuse/dependence. HRQOL in our sample was compared to published reports for the general population as well as for non-MMT HCV patients. To assess predictors of SF-36 HRQOL, hierarchical multiple regression techniques were used to assess model improvement with four blocks of baseline predictors: Demographics, Medical Severity, Addiction Severity, and Depression Severity. Results: HRQOL scores were significantly lower than scores for the general population and were also lower than scores reported for untreated HCV patients not in MMT. Regression analysis demonstrated a consistent pattern whereby Depression Severity increased predictive accuracy for HRQOL measures over simpler models. Beck Depression Inventory scores significantly predicted quality of life across both the mental and physical composite scores and all eight sub-scales of the SF-36. Conclusions: Untreated HCV patients in MMT had lower HRQOL than HCV patients not in MMT. Depression Severity was associated with significantly lower quality of life measures, suggesting that psychiatric evaluation and intervention prior to the start of HCV treatment may improve overall quality of life and could influence HCV treatment outcomes in MMT patients. (C) Published by Elsevier Ireland Ltd. C1 [Batki, Steven L.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Psychiat, Addict Psychiat Res Program, San Francisco, CA 94121 USA. [Canfield, Kelly M.; Smyth, Emily] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Ploutz-Snyder, Robert] Univ Space Res Assoc, NASA JSC, Lyndon B Johnson Space Ctr, SK, Houston, TX 77058 USA. RP Batki, SL (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Psychiat, Addict Psychiat Res Program, 4150 Clement St,116P, San Francisco, CA 94121 USA. EM steven.batki@ucsf.edu FU National Institute on Drug Abuse (NIDA) [R01 DA 016764] FX This work was supported by National Institute on Drug Abuse (NIDA) grant R01 DA 016764. NIDA had no further role in study design; in the collection, analysis, and interpretation of the data; in the writing of this report; and in the decision to Submit the paper for publication. NR 48 TC 11 Z9 11 U1 4 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY 1 PY 2009 VL 101 IS 3 BP 176 EP 182 DI 10.1016/j.drugalcdep.2008.12.012 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 430PY UT WOS:000265002200006 PM 19233573 ER PT J AU Moghissi, ES Korytkowski, MT DiNardo, M Einhorn, D Hellman, R Hirsch, IB Inzucchi, SE Ismail-Beigi, F Kirkman, MS Umpierrez, GE AF Moghissi, Etie S. Korytkowski, Mary T. DiNardo, Monica Einhorn, Daniel Hellman, Richard Hirsch, Irl B. Inzucchi, Silvio E. Ismail-Beigi, Faramarz Kirkman, M. Sue Umpierrez, Guillermo E. TI AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN DIABETES ASSOCIATION CONSENSUS STATEMENT ON INPATIENT GLYCEMIC CONTROL SO ENDOCRINE PRACTICE LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; INTENSIVE-CARE-UNIT; CRITICALLY-ILL PATIENTS; INSULIN INFUSION PROTOCOL; SLIDING-SCALE INSULIN; RANDOMIZED CONTROLLED-TRIAL; ENTERAL NUTRITION THERAPY; TRAUMATIC BRAIN-INJURY; TIGHT GLUCOSE CONTROL; SHORT-TERM MORTALITY C1 [Moghissi, Etie S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Korytkowski, Mary T.] Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA USA. [DiNardo, Monica] Univ Pittsburgh, Sch Nursing, PhD Program, Pittsburgh, PA 15261 USA. [DiNardo, Monica] Vet Affairs Pittsburgh Hlth Ctr, Div Endocrinol & Metab, Pittsburgh, PA USA. [Einhorn, Daniel] Scripps Whittier Diabet Inst, La Jolla, CA USA. [Einhorn, Daniel] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Einhorn, Daniel] Diabet & Endocrine Associates, La Jolla, CA USA. [Hellman, Richard] Univ Missouri Kansas City, Dept Med, Sch Med, Kansas City, MO USA. [Hellman, Richard] Hellman & Rosen Endocrine Associates, Kansas City, MO USA. [Hirsch, Irl B.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Inzucchi, Silvio E.] Yale Univ, Sch Med, Dept Med, Endocrinol Sect, New Haven, CT 06510 USA. [Inzucchi, Silvio E.] Yale New Haven Med Ctr, Yale Diabet Ctr, New Haven, CT 06504 USA. [Ismail-Beigi, Faramarz] Case Western Reserve Univ, Dept Physiol & Med Biophys, Div Clin & Mol Endocrinol, Cleveland, OH 44106 USA. [Kirkman, M. Sue] Amer Diabet Assoc, Clin Affairs, Alexandria, VA USA. [Umpierrez, Guillermo E.] Emory Univ, Dept Med Endocrinol, Atlanta, GA 30322 USA. RP Moghissi, ES (reprint author), 4644 Lincoln Blvd,Suite 409, Marina Del Rey, CA 90292 USA. NR 167 TC 188 Z9 211 U1 2 U2 6 PU AMER ASSOC CLIN ENDOCRINOL PI JACKSONVILLE PA 1000 RIVERSIDE AVE, STE 205, JACKSONVILLE, FL 32204 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD MAY-JUN PY 2009 VL 15 IS 4 BP 353 EP 369 DI 10.4158/EP09102.RA PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 459ZB UT WOS:000267151600013 PM 19454396 ER PT J AU Ganda, OP AF Ganda, Om P. TI REFINING LIPOPROTEIN ASSESSMENT IN DIABETES: APOLIPOPROTEIN B MAKES SENSE SO ENDOCRINE PRACTICE LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; TREATMENT PANEL-III; CARDIOVASCULAR-DISEASE; RISK-FACTORS; SEX DISPARITIES; STATIN THERAPY; CHOLESTEROL; MEN; WOMEN AB Objective: To summarize the data that support the measurement of apolipoprotein B as an accurate reflection of low-density lipoprotein (LDL) particle number and an easily adapted parameter in clinical practice. Methods: Study findings are reviewed and a flow chart is provided to guide lipid assessment in patients with dyslipidemia. Results: Current treatment guidelines for lipid management emphasize LDL cholesterol as the primary treatment target in patients at high risk of cardiovascular events. However, LDL cholesterol is a poor surrogate for LDL particle number, particularly in patients with altered LDL composition, such as those with insulin resistance, metabolic syndrome, and type 2 diabetes. Direct measurement of LDL particle number or size is not practical because of methodology and cost considerations. A suggested alternative target in patients with hypertriglyceridemia is non-high-density lipoprotein (HDL) cholesterol. Abundant evidence suggests that even non-HDL cholesterol is an inadequate approximation of the LDL particle number in such patients. The flow chart emphasizes the need to continue achieving the well-established LDL-cholesterol goal, while also considering apolipoprotein B measurement in those with hypertriglyceridemia, rather than relying on the less accurate surrogate of non-HDL cholesterol, when targeting therapy in such patients. Conclusion: Presented evidence supports the measurement of apolipoprotein B as a more accurate reflection of LDL particle number than non-HDL cholesterol, and it is an easily adapted parameter in clinical practice. (Endocr Pract. 2009;15:370-376) C1 [Ganda, Om P.] Joslin Diabet Ctr, Sect Adult Med, Boston, MA 02215 USA. [Ganda, Om P.] Joslin Diabet Ctr, Sect Clin Res, Boston, MA 02215 USA. [Ganda, Om P.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Ganda, Om P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Ganda, OP (reprint author), Joslin Clin, 1 Joslin Pl,Rm 242, Boston, MA 02215 USA. EM om.ganda@joslin.harvard.edu NR 31 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC CLIN ENDOCRINOL PI JACKSONVILLE PA 1000 RIVERSIDE AVE, STE 205, JACKSONVILLE, FL 32204 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD MAY-JUN PY 2009 VL 15 IS 4 BP 370 EP 376 DI 10.4158/EP09064.RAR PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 459ZB UT WOS:000267151600014 PM 19454383 ER PT J AU Emamaullee, JA Merani, S Toso, C Kin, T Al-Saif, F Truong, W Pawlick, R Davis, J Edgar, R Lock, J Bonner-Weir, S Knudsen, LB Shapiro, AMJ AF Emamaullee, Juliet A. Merani, Shaheed Toso, Christian Kin, Tatsuya Al-Saif, Faisal Truong, Wayne Pawlick, Rena Davis, Joy Edgar, Ryan Lock, Jennifer Bonner-Weir, Susan Knudsen, Lotte B. Shapiro, A. M. James TI Porcine Marginal Mass Islet Autografts Resist Metabolic Failure Over Time and Are Enhanced by Early Treatment with Liraglutide SO ENDOCRINOLOGY LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; SHORT-TERM; TRANSPLANTATION; APOPTOSIS; SURVIVAL; ANALOG; THERAPY; MICE AB Although insulin independence is maintained in most islet recipients at 1 yr after transplant, extended follow-up has revealed that many patients will eventually require insulin therapy. Previous studies have shown that islet autografts are prone to chronic failure in large animals and humans, suggesting that nonimmunological events contribute to islet graft functional decay. Early intervention with therapies that promote graft stability should provide a measurable benefit over time. In this study, the efficacy of the long-acting glucagon-like peptide-1 analog liraglutide was explored in a porcine marginal mass islet autograft transplant model. Incubation with liraglutide enhanced porcine islet survival and function after prolonged culture. Most vehicle-treated (83%) and liraglutide-treated (80%) animals became insulin independent after islet autotransplantation. Although liraglutide therapy did not improve insulin independence rates or blood glucose levels after transplant, a significant increase in insulin secretion and acute-phase insulin response was observed in treated animals. Surprisingly, no evidence for deterioration of graft function was observed in any of the transplanted animals over more than 18 months of follow-up despite significant weight gain; in fact, an enhanced response to glucose developed over time even in control animals. Histological analysis showed that intraportally transplanted islets remained highly insulin positive, retained alpha-cells, and did not form amyloid deposits. This study demonstrates that marginal mass porcine islet autografts have stable long-term function, even in the presence of an increasing metabolic demand. These results are discrepant with previous large animal studies and suggest that porcine islets may be resistant to metabolic failure. (Endocrinology 150: 2145-2152, 2009) C1 [Emamaullee, Juliet A.; Merani, Shaheed; Toso, Christian; Al-Saif, Faisal; Truong, Wayne; Davis, Joy; Edgar, Ryan; Shapiro, A. M. James] Univ Alberta, Dept Surg, Edmonton, AB T6G 2E1, Canada. [Kin, Tatsuya; Pawlick, Rena; Shapiro, A. M. James] Univ Alberta, Clin Islet Transplant Program, Edmonton, AB T6G 2E1, Canada. [Lock, Jennifer; Bonner-Weir, Susan] Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. [Knudsen, Lotte B.] Novo Nordisk AS, DK-2880 Bagsvaerd, Denmark. RP Emamaullee, JA (reprint author), Univ Alberta, Dept Surg, 5-126 HRIF E, Edmonton, AB T6G 2E1, Canada. EM juliete@ualberta.ca RI Kin, Tatsuya /A-3776-2012; OI Kin, Tatsuya /0000-0002-5179-6067; Emamaullee, Juliet/0000-0003-4238-3057 FU American Society for Transplantation; Juvenile Diabetes Research Foundation; Alberta Heritage Foundation for Medical Research (AHFMR); Rhind Autoimmunology Award; Canadian Institutes for Health Research; Swiss National Science Foundation [11859311]; FS Chia Scholarship FX J.E. is supported by fellowships from the American Society for Transplantation, Juvenile Diabetes Research Foundation, and Alberta Heritage Foundation for Medical Research (AHFMR) and by the Rhind Autoimmunology Award. S.M. is supported by studentship awards from the AHFMR and the Canadian Institutes for Health Research. C.T. is the recipient of Grant 11859311 of the Swiss National Science Foundation, FS Chia Scholarship, and an AHFMR fellowship. A.M.J.S is an AHFMR Scholar. NR 32 TC 26 Z9 27 U1 0 U2 1 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 MAY PY 2009 VL 150 IS 5 BP 2145 EP 2152 DI 10.1210/en.2008-1116 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436IQ UT WOS:000265407500016 PM 19131571 ER PT J AU Page, JH Rexrode, KM Hu, F Albert, CM Chae, CU Manson, JE AF Page, John H. Rexrode, Kathryn M. Hu, Frank Albert, Christine M. Chae, Claudia U. Manson, JoAnn E. TI Waist-Height Ratio as a Predictor of Coronary Heart Disease Among Women SO EPIDEMIOLOGY LA English DT Article ID INSULIN-RESISTANCE; RISK-FACTORS; MEN; OBESITY; REMOVAL; FOLLOW; INDEX; DEATH AB Background: It is not yet established what specific measures of obesity might be most strongly associated with risk of coronary artery disease. We compared the waist-height ratio to waist-hip ratio, waist circumference, and body mass index as predictors of subsequent coronary heart disease (CHD) in a group of predominantly postmenopausal women. Methods: The data come from the prospective Nurses' Health Study cohort. We included 45,563 women in 1986 who were aged 40-65 years and were free of heart disease, stroke, and cancer. Waist circumference, hip circumference, height, weight, age, and other covariates were collected by questionnaire. Our primary end point was incident coronary heart disease reported up to June 2002. Areas under the receiver operating characteristic curves (AUCs) were estimated nonparametrically for each of the anthropometric measures. We estimated differences between the AUCs for weight-height ratio and the other measures, with corresponding 95% confidence intervals. We used Cox proportional hazard models to estimate the relationships with risk of CHD. Results: Waist-height ratio, waist-hip ratio, and waist circumference were similar in predicting subsequent risk of CHD. All 3 waist-derived measures were superior to body-mass index (BMI) in predicting CHD. The unadjusted AUCs were 0.62 (95% confidence interval = 0.60-0.64) for waist-height ratio, 0.63 (0.61-0.65) for waist-hip ratio, 0.62 (0.60-0.64) for waist-circumference, and 0.57 (0.55-0.59) for BMI. C1 [Page, John H.; Hu, Frank; Manson, JoAnn E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chae, Claudia U.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Rexrode, Kathryn M.; Albert, Christine M.; Chae, Claudia U.; Manson, JoAnn E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, Boston, MA 02115 USA. [Hu, Frank; Manson, JoAnn E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Albert, Christine M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Hu, Frank] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Page, JH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM john_page@post.harvard.edu OI Rexrode, Kathryn/0000-0003-3387-8429 FU National Heart Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services [HL34594]; American Heart Association [0475016N] FX Supported by Public Health Service grant HL34594 from the National Heart Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services, and the American Heart Association award 0475016N (to J. H. P). NR 26 TC 22 Z9 23 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2009 VL 20 IS 3 BP 361 EP 366 DI 10.1097/EDE.0b013e31819f38f1 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 433JJ UT WOS:000265199800010 PM 19289960 ER PT J AU Hope, OA Zeber, JE Kressin, NR Bokhour, BG VanCott, AC Cramer, JA Amuan, ME Knoefel, JE Pugh, MJ AF Hope, Omotola A. Zeber, John E. Kressin, Nancy R. Bokhour, Barbara G. VanCott, Anne C. Cramer, Joyce A. Amuan, Megan E. Knoefel, Janice E. Pugh, Mary Jo TI New-onset geriatric epilepsy care: Race, setting of diagnosis, and choice of antiepileptic drug SO EPILEPSIA LA English DT Article DE Race; Ethnicity; Geriatric epilepsy treatment; Healthcare quality; Medical specialties ID QUALITY-OF-LIFE; HEALTH-CARE; MYOCARDIAL-INFARCTION; EMERGENCY-DEPARTMENT; SERUM CONCENTRATIONS; ADMINISTRATIVE DATA; RACIAL DISPARITIES; ELDERLY-PATIENTS; DOUBLE-BLIND; RISK-FACTORS AB There is a growing movement to assess the quality of care provided to patients in the US, but few studies have examined initial care for epilepsy patients. We examined the relationships among patient race, setting of initial diagnosis, and initial treatment for older veterans newly diagnosed with epilepsy. We used Department of Veterans Affairs (VA) inpatient, outpatient, pharmacy and Medicare data (1999-2004) to identify patients 66 years and older with new-onset epilepsy. High quality care was defined as avoiding a suboptimal agent (phenytoin, phenobarbital, primidone) as defined by experts. Predictors included demographic and clinical characteristics, and the context of the initial seizure diagnosis including the setting (e.g. emergency, neurology, hospital, primary care). We used mixed-effects multivariable logistic regression modeling to identify predictors of initial seizure diagnosis in a neurology setting, and receipt of a suboptimal AED. Of 9,682 patients, 27% were initially diagnosed in neurology and 70% received a suboptimal AED. Blacks and Hispanics were less likely to be diagnosed in neurology clinics (black OR = 0.7 95% CI 0.6-0.8; Hispanic OR = 0.6 95% CI 0.5-0.9). Diagnosis in a non-neurology setting increased the likelihood of receiving a suboptimal agent (e.g. Emergency Department OR = 2.3 95% CI 2.0-2.7). After controlling for neurology diagnosis, black race was independently associated with an increased risk of receiving a suboptimal agent. We demonstrated that differences in quality of care exist for both clinical setting of initial diagnosis and race. We discussed possible causes and implications of these findings. C1 [Pugh, Mary Jo] S Texas Vet Hlth Care Syst VERDICT, Audie L Murphy Div 11C6, Vet Affairs HSR&D, San Antonio, TX 78229 USA. [Hope, Omotola A.] Univ Texas Hlth Sci Ctr Houston, Dept Neurol, Houston, TX USA. [Zeber, John E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Kressin, Nancy R.; Bokhour, Barbara G.; Amuan, Megan E.] Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Kressin, Nancy R.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Bokhour, Barbara G.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [VanCott, Anne C.] VA Pittsburgh Healthcare Syst, Div Neurol, Pittsburgh, PA USA. [VanCott, Anne C.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Cramer, Joyce A.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Cramer, Joyce A.] Epilepsy Therapy Project, Orange, CT USA. [Knoefel, Janice E.] New Mexico Vet Healthcare Syst, Med Serv, Albuquerque, NM USA. [Knoefel, Janice E.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Knoefel, Janice E.] Univ New Mexico, Dept Neurol, Albuquerque, NM 87131 USA. [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Gen Med, San Antonio, TX 78229 USA. RP Pugh, MJ (reprint author), S Texas Vet Hlth Care Syst VERDICT, Audie L Murphy Div 11C6, Vet Affairs HSR&D, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM pughm@uthscsa.edu OI Bokhour, Barbara/0000-0001-8238-0745; Kressin, Nancy/0000-0003-2767-4286; Pugh, Mary Jo/0000-0003-4196-7763 FU VA Health Services Research and Development Service [IIR 02-274]; Robert Wood Johnson Clinical Scholars Fellowship; Department of Veterans Affairs, Health Services Research and Development Service [RCS 02-066-1] FX Disclosure of conflicts of interest: Anne C. VanCott has research funding from GlaxoSmithKline. Joyce Cramer has been a consultant to Johnson and Johnson, Pfizer, Sepracor and UCB Pharma. The other authors report no conflicts of interest. NR 62 TC 14 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2009 VL 50 IS 5 BP 1085 EP 1093 DI 10.1111/j.1528-1167.2008.01892.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 441LG UT WOS:000265770000016 PM 19054416 ER PT J AU Muzykewicz, DA Lyczkowski, DA Memon, N Conant, KD Pfeifer, HH Thiele, EA AF Muzykewicz, David A. Lyczkowski, David A. Memon, Naureen Conant, Kerry D. Pfeifer, Heidi H. Thiele, Elizabeth A. TI Efficacy, safety, and tolerability of the low glycemic index treatment in pediatric epilepsy SO EPILEPSIA LA English DT Article DE Low glycemic index treatment; Pediatric epilepsy; Efficacy; Safety; Tolerability ID KETOGENIC DIET; SEIZURE SUSCEPTIBILITY; BETA-HYDROXYBUTYRATE; LIPID PROFILE; KETONE-BODIES; GLUCOSE; METABOLISM; THRESHOLD; CHILDREN; KETOSIS AB To report the efficacy, safety, and tolerability of the low glycemic index treatment (LGIT) in pediatric epilepsy. A retrospective chart review was performed on patients initiating the LGIT at the Massachusetts General Hospital between January 2002 and June 2008. Demographic and clinical information including seizure type, baseline seizure frequency, medications, blood chemistries, side effects, and anthropometrics were collected. Initiation of the LGIT was done in an outpatient setting. Patients were educated by a dietitian to restrict foods with high glycemic index and to limit total daily carbohydrates to 40-60 g. Change in seizure frequency was assessed at 1-, 3-, 6-, 9-, and 12-month follow-up intervals. Seventy-six children were included in the study. Eighty-nine percent had intractable epilepsy (>= 3 antiepileptic drugs). A greater than 50% reduction from baseline seizure frequency was observed in 42%, 50%, 54%, 64%, and 66% of the population with follow-up available at 1, 3, 6, 9, and 12 months, respectively. Increased efficacy was correlated with lower serum glucose levels at some time points, but not with beta-hydroxybutyrate (BOHB) changes or ketosis status at any time point. Only three patients reported side effects (transient lethargy). Blood urea nitrogen (BUN) was elevated in approximately one-third of follow-up laboratory studies. No significant changes were seen in body mass index (BMI) or BMI z-score at any follow-up interval. The most cited reason for treatment discontinuation was the restrictiveness of the diet, in 18 patients (24%). The LGIT was associated with reduced seizure frequency in a large fraction of patients, with limited side effects. C1 [Muzykewicz, David A.; Lyczkowski, David A.; Memon, Naureen; Conant, Kerry D.; Pfeifer, Heidi H.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Pediat Epilepsy Program, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org NR 34 TC 62 Z9 66 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2009 VL 50 IS 5 BP 1118 EP 1126 DI 10.1111/j.1528-1167.2008.01959.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 441LG UT WOS:000265770000020 PM 19220406 ER PT J AU Burneo, JG Del Brutto, O Delgado-Escueta, AV Gonzalez, AE Medina, MT Montano, SM Moyano, LM Nash, T Roman, G Singh, G White, AC Wiebe, S Garcia, HH AF Burneo, Jorge G. Del Brutto, Oscar Delgado-Escueta, Antonio V. Gonzalez, Armando E. Medina, Marco T. Montano, Silvia M. Moyano, Luz M. Nash, Theodore Roman, Gustavo Singh, Gagandeep White, A. Clinton, Jr. Wiebe, Samuel Garcia, Hector H. TI Workshop Report: Developing an international collaborative research network in neurocysticercosis and epilepsy SO EPILEPSIA LA English DT Editorial Material C1 [Burneo, Jorge G.] Univ Western Ontario, Epilepsy Programme, London, ON, Canada. [Del Brutto, Oscar] Hosp Clin Kennedy, Guayaquil, Ecuador. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, Epilepsy Ctr Excellence, VA Greater Healthcare Syst, Los Angeles, CA USA. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gonzalez, Armando E.] Univ Nacl Mayor San Marcos, Sch Vet Med, Lima 14, Peru. [Gonzalez, Armando E.; Moyano, Luz M.; Garcia, Hector H.] Cysticercosis Eliminat Project, Tumbes, Peru. [Gonzalez, Armando E.; Garcia, Hector H.] Inst Peruano Parasitol Clin & Expt, Lima, Peru. [Medina, Marco T.] Univ Autonoma Honduras, Tegucigalpa, Honduras. [Montano, Silvia M.] US Naval Res Detachment, Lima, Peru. [Moyano, Luz M.; Garcia, Hector H.] Univ Peruana Cayetano Heredia, Lima, Peru. [Nash, Theodore] Natl Inst Hlth, Bethesda, MD USA. [Roman, Gustavo] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Singh, Gagandeep] Dayanand Med Coll, Ludhiana, Punjab, India. [White, A. Clinton, Jr.] Univ Texas Galveston, Med Branch, Galveston, TX 77550 USA. [Wiebe, Samuel] Univ Calgary, Dept Neurosci, Calgary, AB, Canada. [Garcia, Hector H.] Inst Ciencias Neurol, Dept Transmissible Dis, Lima, Peru. RP Burneo, JG (reprint author), Univ Western Ontario, Epilepsy Programme, London, ON, Canada. EM jburneo2@uwo.ca OI White, A Clinton/0000-0002-9668-4632; Delgado-Escueta, Antonio V./0000-0002-1581-6999 FU Intramural NIH HHS [ZIA AI000846-15] NR 7 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2009 VL 50 IS 5 BP 1289 EP 1290 DI 10.1111/j.1528-1167.2008.01912.x PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 441LG UT WOS:000265770000043 PM 19496808 ER PT J AU Burneo, JG Del Brutto, O Delgado-Escueta, AV Gonzalez, AE Medina, MT Montano, SM Moyano, LM Nash, T Roman, G Singh, G White, AC Wiebe, S Garcia, HH AF Burneo, Jorge G. Del Brutto, Oscar Delgado-Escueta, Antonio V. Gonzalez, Armando E. Medina, Marco T. Montano, Silvia M. Moyano, Luz M. Nash, Theodore Roman, Gustavo Singh, Gagandeep White, A. Clinton, Jr. Wiebe, Samuel Garcia, Hector H. TI Benign myoclonus of early infancy or Fejerman syndrome SO EPILEPSIA LA English DT Editorial Material ID SPASMS C1 [Burneo, Jorge G.] Univ Western Ontario, Epilepsy Programme, London, ON, Canada. [Del Brutto, Oscar] Hosp Clin Kennedy, Guayaquil, Ecuador. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, Epilepsy Ctr Excellence, VA Greater Healthcare Syst, Los Angeles, CA USA. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gonzalez, Armando E.] Univ Nacl Mayor San Marcos, Sch Vet Med, Lima 14, Peru. [Gonzalez, Armando E.; Moyano, Luz M.; Garcia, Hector H.] Cysticercosis Eliminat Project, Tumbes, Peru. [Gonzalez, Armando E.; Garcia, Hector H.] Inst Peruano Parasitol Clin & Expt, Lima, Peru. [Medina, Marco T.] Univ Autonoma Honduras, Tegucigalpa, Honduras. [Montano, Silvia M.] US Naval Res Detachment, Lima, Peru. [Moyano, Luz M.; Garcia, Hector H.] Univ Peruana Cayetano Heredia, Lima, Peru. [Nash, Theodore] Natl Inst Hlth, Bethesda, MD USA. [Roman, Gustavo] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Singh, Gagandeep] Dayanand Med Coll, Ludhiana, Punjab, India. [White, A. Clinton, Jr.] Univ Texas Galveston, Med Branch, Galveston, TX 77550 USA. [Wiebe, Samuel] Univ Calgary, Dept Neurosci, Calgary, AB, Canada. [Garcia, Hector H.] Inst Ciencias Neurol, Dept Transmissible Dis, Lima, Peru. RP Burneo, JG (reprint author), Univ Western Ontario, Epilepsy Programme, London, ON, Canada. EM jburneo2@uwo.ca NR 16 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2009 VL 50 IS 5 BP 1290 EP 1292 DI 10.1111/j.1528-1167.2009.02154.x PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 441LG UT WOS:000265770000044 ER PT J AU Balajee, SA Baddley, JW Peterson, SW Nickle, D Varga, J Boey, A Lass-Florl, C Frisvad, JC Samson, RA AF Balajee, S. Arunmozhi Baddley, John W. Peterson, Stephen W. Nickle, David Varga, Janos Boey, Angeline Lass-Floerl, Cornelia Frisvad, Jens C. Samson, Robert A. CA ISHAM Working Grp A Terreus TI Aspergillus alabamensis, a New Clinically Relevant Species in the Section Terrei SO EUKARYOTIC CELL LA English DT Article ID PULMONARY ASPERGILLOSIS; POLYPHASIC TAXONOMY; FUMIGATUS; NEOSARTORYA; EPIDEMIOLOGY; INFECTIONS; EXPERIENCE AB Phylogenetic analyses of sequences generated from portions of three genes coding for the proteins enolase (enoA), beta-tubulin (benA), and calmodulin (calM) of a large number of isolates within the section Terrei, genus Aspergillus, revealed the presence of a new cryptic species within this section, Aspergillus alabamensis. Most members of this new cryptic species were recovered as colonizing isolates from immunocompetent patient populations, had decreased in vitro susceptibilities to the antifungal drug amphotericin B, and were morphologically similar to but genetically distinct from Aspergillus terreus isolates. C1 [Balajee, S. Arunmozhi; Boey, Angeline] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA 30333 USA. [Baddley, John W.] Univ Alabama, Div Infect Dis, Birmingham, W Midlands, England. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Peterson, Stephen W.] USDA, Natl Ctr Agr Utilizat Res, Peoria, IL USA. [Nickle, David] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Varga, Janos; Samson, Robert A.] CBS Fungal Biodivers Ctr, Utrecht, Netherlands. [Varga, Janos] Univ Szeged, Dept Microbiol, Fac Sci & Informat, Szeged, Hungary. [Lass-Floerl, Cornelia] Med Univ Innsbruck, Dept Hyg Microbiol & Social Med, Innsbruck, Austria. [Frisvad, Jens C.] Tech Univ Denmark, Ctr Microbial Biotechnol, Biocentrum DTU, DK-2800 Lyngby, Denmark. RP Balajee, SA (reprint author), Ctr Dis Control & Prevent, Mycot Dis Branch, Mail Stop G11,1600 Clifton Rd, Atlanta, GA 30333 USA. EM fir3@cdc.gov RI Dijksterhuis, Jan/K-5945-2014 OI Dijksterhuis, Jan/0000-0002-2649-1704 NR 18 TC 29 Z9 30 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD MAY PY 2009 VL 8 IS 5 BP 713 EP 722 DI 10.1128/EC.00272-08 PG 10 WC Microbiology; Mycology SC Microbiology; Mycology GA 443JM UT WOS:000265906000004 PM 19304950 ER PT J AU Tampakakis, E Peleg, AY Mylonakis, E AF Tampakakis, Emmanouil Peleg, Anton Y. Mylonakis, Eleftherios TI Interaction of Candida albicans with an Intestinal Pathogen, Salmonella enterica Serovar Typhimurium SO EUKARYOTIC CELL LA English DT Article ID CAENORHABDITIS-ELEGANS; INFECTIONS; MORPHOLOGY; MUTANTS; HOMOLOG; GENES; HOST AB Candida albicans is an opportunistic human fungal pathogen that normally resides in the gastrointestinal tract and on the skin as a commensal but can cause life-threatening invasive disease. Salmonella enterica serovar Typhimurium is a gram-negative bacterial pathogen that causes a significant amount of gastrointestinal infection in humans. Both of these organisms are also pathogenic to the nematode Caenorhabditis elegans, causing a persistent gut infection leading to worm death. In the present study, we used a previously developed C. elegans polymicrobial infection model to assess the interactions between S. Typhimurium and C. albicans. We observed that when C. elegans is infected with C. albicans and serovar Typhimurium, C. albicans filamentation is inhibited. The inhibition of C. albicans filamentation by S. Typhimurium in C. elegans appeared to be mediated by a secretary molecule, since filter-sterilized bacterial supernatant was able to inhibit C. albicans filamentation. In vitro coculture assays under planktonic conditions showed that S. Typhimurium reduces the viability of C. albicans, with greater effects seen at 37 C than at 30 C. Interestingly, S. Typhimurium reduces the viability of both yeast and filamentous forms of C. albicans, but the killing appeared more rapid for the filamentous cells. The antagonistic interaction was also observed in a C. albicans biofilm environment. This study describes the interaction between two diverse human pathogens that reside within the gastrointestinal tract and shows that the prokaryote, S. Typhimurium, reduces the viability of the eukaryote, C. albicans. Identifying the molecular mechanisms of this interaction may provide important insights into microbial pathogenesis. C1 [Tampakakis, Emmanouil; Peleg, Anton Y.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Peleg, Anton Y.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Peleg, Anton Y.; Mylonakis, Eleftherios] Harvard Univ, Sch Med, Boston, MA 02214 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org OI Peleg, Anton/0000-0002-2296-2126 FU National Institutes of Health R01 award [AI075286]; University of Queensland postgraduate scholarship award FX Support was provided by National Institutes of Health R01 award AI075286 (to E. M.) and a University of Queensland postgraduate scholarship award (to A. Y. P.). NR 23 TC 37 Z9 37 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD MAY PY 2009 VL 8 IS 5 BP 732 EP 737 DI 10.1128/EC.00016-09 PG 6 WC Microbiology; Mycology SC Microbiology; Mycology GA 443JM UT WOS:000265906000006 PM 19329669 ER PT J AU Bhatt, DL Peterson, ED Harrington, RA Ou, FS Cannon, CP Gibson, CM Kleiman, NS Brindis, RG Peacock, WF Brener, SJ Menon, V Smith, SC Pollack, CV Gibler, WB Ohman, EM Roe, MT AF Bhatt, Deepak L. Peterson, Eric D. Harrington, Robert A. Ou, Fang-Shu Cannon, Christopher P. Gibson, C. Michael Kleiman, Neal S. Brindis, Ralph G. Peacock, W. Frank Brener, Sorin J. Menon, Venu Smith, Sidney C., Jr. Pollack, Charles V., Jr. Gibler, W. Brian Ohman, E. Magnus Roe, Matthew T. CA CRUSADE Investigators TI Prior polyvascular disease: risk factor for adverse ischaemic outcomes in acute coronary syndromes SO EUROPEAN HEART JOURNAL LA English DT Article DE Acute coronary syndromes; Coronary artery disease; Cerebrovascular disease; Peripheral arterial disease ID PERIPHERAL ARTERIAL-DISEASE; VASCULAR-DISEASE; MYOCARDIAL-INFARCTION; INTERVENTION; ATHEROTHROMBOSIS; OUTPATIENTS; AWARENESS; EVENTS; STROKE AB The presence of peripheral arterial disease (PAD) or cerebrovascular disease (CVD) is associated with higher likelihood of significant coronary artery disease (CAD). We sought to assess the prevalence of PAD, CVD, prior CAD, or pre-existent disease in multiple arterial territories ('polyvascular' disease) in patients presenting with non-ST-segment elevation acute coronary syndrome and its impact on adverse events. Data from 95 749 patients enrolled from February 2003 to September 2006 at 484 sites in the CRUSADE registry were analysed. Patients were categorized as having prior 0, 1, 2, or 3 affected arterial beds. The rates of in-hospital mortality, myocardial infarction, stroke, and congestive heart failure were analysed, as were the rates of non-bypass surgery-related red blood cell transfusion and major bleeding. On presentation, 11 345 (11.9%) patients had established PAD, 9973 (10.4%) had documented CVD, and 41 404 (43.2%) had prior CAD. In this cohort, 0, 1, 2, and 3 arterial bed disease before presentation was present in 46 814 (48.9%, 95% CI 48.6-49.2%), 36 704 (38.3%, 95% CI 37.8-39.0%), 10 675 (11.2%, 95% CI 10.9-11.9%), and 1556 (1.6%, 95% CI 1.5-1.8%) patients, respectively. The rates of ischaemic events increased with the number of affected vascular beds. The adjusted odds ratio for the composite of in-hospital ischaemic events for pre-existent disease in 1, 2, or 3 arterial beds (compared with 0 arterial bed involvement) increased from 1.07 to 1.26 to 1.31 (P < 0.001). Similarly, the adjusted odds ratio for transfusion increased with greater disease burden from 1.11 to 1.28 to 1.30 (P < 0.001), although the adjusted rates of protocol-defined non-bypass surgery-related major bleeding did not. Prior polyvascular disease increases the risk of in-hospital adverse events, including mortality. Identification of these patients in clinical trial and real world populations may provide an opportunity to reduce their excess risk with intensive secondary prevention efforts. C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.; Cannon, Christopher P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Peterson, Eric D.; Harrington, Robert A.; Ou, Fang-Shu; Ohman, E. Magnus; Roe, Matthew T.] Duke Clin Res Inst, Durham, NC USA. [Cannon, Christopher P.] Harvard Univ, Sch Med, TIMI Study Grp, Boston, MA USA. [Gibson, C. Michael] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kleiman, Neal S.] Methodist DeBakey Heart Ctr, Houston, TX USA. [Brindis, Ralph G.] Kaiser Permanente Hlth Syst, San Francisco, CA USA. [Peacock, W. Frank; Menon, Venu] Cleveland Clin, Cleveland, OH 44106 USA. [Brener, Sorin J.] New York Methodist Hosp, Brooklyn, NY USA. [Smith, Sidney C., Jr.] Univ N Carolina, Chapel Hill, NC USA. [Pollack, Charles V., Jr.] Penn Hosp, Philadelphia, PA 19107 USA. [Gibler, W. Brian] Univ Cincinnati, Cincinnati, OH USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM dlbhattmd@alum.mit.edu FU Schering-Plough Corporation; Millennium Pharmaceuticals, Inc. FX CRUSADE is a national quality improvement initiative of the Duke Clinical Research Institute. CRUSADE is funded by the Schering-Plough Corporation. Bristol-Myers Squibb/sanofi-aventis Pharmaceuticals Partnership provides additional funding support. Millennium Pharmaceuticals, Inc. also provided funding for this work. NR 23 TC 59 Z9 61 U1 0 U2 3 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 MAY PY 2009 VL 30 IS 10 BP 1195 EP 1202 DI 10.1093/eurheartj/ehp099 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 446IL UT WOS:000266115200009 PM 19339264 ER PT J AU Preza, D Olsen, I Willumsen, T Boches, SK Cotton, SL Grinde, B Paster, BJ AF Preza, D. Olsen, I. Willumsen, T. Boches, S. K. Cotton, S. L. Grinde, B. Paster, B. J. TI Microarray analysis of the microflora of root caries in elderly SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID BACTERIAL DIVERSITY; MOLECULAR ANALYSIS; DENTAL-CARIES; SURFACES AB The present study used a new 16S rRNA-based microarray with probes for over 300 bacterial species to better define the bacterial profiles of healthy root surfaces and root caries (RC) in the elderly. Supragingival plaque was collected from 20 healthy subjects (Controls) and from healthy and carious roots and carious dentin from 21 RC subjects (Patients). Collectively, 179 bacterial species and species groups were detected. A higher bacterial diversity was observed in Controls than in Patients. Lactobacillus casei/paracasei/rhamnosus and Pseudoramibacter alactolyticus were notably associated with most RC samples. Streptococcus mutans was detected more frequently in the infected dentin than in the other samples, but the difference was not significant. Actinomyces was found more frequently in Controls. Thus, species other than Actinomyces and S. mutans may play a role as pathogens of RC. The results from this study were in general agreement with those of our previous study based on 16S rRNA gene sequencing. C1 [Preza, D.; Olsen, I.; Grinde, B.] Univ Oslo, Fac Dent, Inst Oral Biol, N-0316 Oslo, Norway. [Willumsen, T.] Univ Oslo, Fac Dent, Dept Gerodontol, N-0316 Oslo, Norway. [Grinde, B.] Norwegian Inst Publ Hlth, Oslo, Norway. [Boches, S. K.; Cotton, S. L.; Paster, B. J.] Forsyth Inst, Dept Mol Genet, Boston, MA USA. [Paster, B. J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Preza, D (reprint author), Univ Oslo, Fac Dent, Inst Oral Biol, Postbox 1052 Blindern, N-0316 Oslo, Norway. EM doritap@odont.uio.no FU Faculty of Dentistry, University of Oslo, Oslo, Norway; NIH [DE11443] FX We thank the Cathinka Guldberg-Centre in Oslo, Norway, particularly Marianne Wenaasen and Sabah Tariq for patient management. We are very thankful to Professor Leiv Sandvik for his statistical advice. The study was supported by the Faculty of Dentistry, University of Oslo, Oslo, Norway and NIH grant DE11443 (B.J.P.). NR 20 TC 43 Z9 47 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD MAY PY 2009 VL 28 IS 5 BP 509 EP 517 DI 10.1007/s10096-008-0662-8 PG 9 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 450ZI UT WOS:000266440100011 PM 19039610 ER PT J AU Salemi, VM Leite, JJ Picard, MH Oliveira, LM Reis, SF Pena, JL Mady, C AF Salemi, Vera M. C. Leite, Joao J. Picard, Michael H. Oliveira, Leila M. Reis, Soraya F. Pena, Jose L. B. Mady, Charles TI Echocardiographic predictors of functional capacity in endomyocardial fibrosis patients SO EUROPEAN JOURNAL OF ECHOCARDIOGRAPHY LA English DT Article DE Endomyocardial fibrosis; Restrictive cardiomyopathy; Echocardiography; Diastole; Ergoespirometry and prognosis ID ATRIAL-FIBRILLATION; DIASTOLIC FUNCTION; HEART-FAILURE; EXERCISE CAPACITY; DOPPLER; CARDIOMYOPATHIES; REGURGITATION; PRESSURE; VELOCITY AB Endomyocardial fibrosis (EMF) is a restrictive cardiomyopathy manifested mainly by diastolic heart failure. It is recognized that diastole is an important determinant of exercise capacity. The purpose of this study was to determine whether resting echocardiographic parameters might predict oxygen consumption (VO(2p)) by ergoespirometry and the prognostic role of functional capacity in EMF patients. A total of 32 patients with biventricular EMF (29 women, 55.3 +/- 11.4 years) were studied by echocardiography and ergoespirometry. The relationship between the echocardiographic indexes and the percentage of predicted VO(2p) (%VO(2p)) was investigated by the 'stepwise' linear regression analysis. The median VO(2p) was 11 +/- 3 mL/kg/min and the %VO(2p) was 53 +/- 9%. There was a correlation of %VO(2p) with an average of A' at four sites of the mitral annulus (A' peak, r = 0.471, P = 0.023), E'/A' of the inferior mitral annulus (r = -0.433, P = 0.044), and myocardial performance index (r = -0.352, P = 0.048). On multiple regression analysis, only A' peak was an independent predictor of %VO(2p) (%VO(2p)= 26.34 + 332.44 x A' peak). EMF patients with %VO(2p)< 53% had an increased mortality rate with a relative risk of 8.47. In EMF patients, diastolic function plays an important role in determining the limitations to exercise and %VO(2p) has a prognostic value. C1 [Salemi, Vera M. C.; Reis, Soraya F.; Pena, Jose L. B.; Mady, Charles] Univ Sao Paulo, Sch Med, Cardiomyopathy Unit, Sao Paulo, Brazil. [Leite, Joao J.; Oliveira, Leila M.] Univ Sao Paulo, Div Pulm, Heart Inst InCor, Sao Paulo, Brazil. [Picard, Michael H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Picard, Michael H.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Picard, Michael H.] Harvard Univ, Sch Med, Boston, MA USA. RP Salemi, VM (reprint author), Univ Sao Paulo, Sch Med, Cardiomyopathy Unit, Sao Paulo, Brazil. EM verasalemi@uol.com.br RI Mady, Charles/C-8870-2012; Salemi, Vera/C-9104-2013; OI Mady, Charles/0000-0002-8838-199X; Salemi, Vera/0000-0002-7152-1810; Picard, Michael/0000-0002-9264-3243 NR 26 TC 4 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1525-2167 J9 EUR J ECHOCARDIOGR JI Eur. J. Echocardiogr. PD MAY PY 2009 VL 10 IS 3 BP 400 EP 405 DI 10.1093/ejechocard/jen297 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 428YZ UT WOS:000264889300010 PM 18952626 ER PT J AU Moore, A AF Moore, Anna TI Advances in beta-cell imaging SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Beta-cells; Islets; MRI; Contrast agents ID IN-VITRO; SULFONYLUREA RECEPTORS; ANTIGEN EXPRESSION; PANCREATIC-ISLETS; FUNCTIONAL-STATE; BB RAT; MASS; FATE; AGENT; ACID AB Diabetes mellitus results in impaired insulin production by pancreatic beta-cells due to their death and/or dysfunction. There is a growing unmet need among diabetes researches and clinicians to assess the level of surviving beta-cells non-invasively. This review will focus on employment of state-of-the-art in vivo imaging methods to estimate and evaluate beta-cell mass in animal models of diabetes. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,MIT,Mol I, Charlestown, MA 02129 USA. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,MIT,Mol I, Bldg 75,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu FU NIH [DK072137, DK58511, DK071225] FX Partial support for the studies described in this review was provided by NIH grants DK072137, DK58511 and DK071225 to A.M. NR 41 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAY PY 2009 VL 70 IS 2 BP 254 EP 257 DI 10.1016/j.ejrad.2009.01.044 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 456SP UT WOS:000266868900008 PM 19261414 ER PT J AU Zietman, A AF Zietman, Anthony TI Re: Endocrine Treatment, with or without Radiotherapy, in Locally Advanced Prostate Cancer (SPCG-7/SFUO-3): An Open Randomised Phase III Trial SO EUROPEAN UROLOGY LA English DT Editorial Material ID ANDROGEN DEPRIVATION; THERAPY C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Fruit St, Boston, MA 02114 USA. EM AZIETMAN@PARTNERS.ORG NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD MAY PY 2009 VL 55 IS 5 BP 1240 EP 1240 DI 10.1016/j.eururo.2009.01.059 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 438YI UT WOS:000265592300052 PM 19650206 ER PT J AU Seltzer, B Pandya, D AF Seltzer, Benjamin Pandya, Deepak N. TI Posterior cingulate and retrosplenial cortex connections of the caudal superior temporal region in the rhesus monkey SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Superior temporal region; Superior temporal gyrus; Superior temporal sulcus; Cingulate cortex; Retrosplenial cortex; Area Tpt; Auditory system ID PARABELT AUDITORY-CORTEX; CORTICAL CONNECTIONS; PREFRONTAL CORTEX; MACAQUE MONKEYS; FRONTAL-CORTEX; INTRINSIC CONNECTIONS; NEURAL CONNECTIONS; ASSOCIATION CORTEX; PARIETAL CORTEX; COMPLEX SOUNDS AB The rostral part of the superior temporal gyrus (STG) is known to project to ventral temporal cortex, but analogous paralimbic connections of the caudal STG have received comparatively less attention. The present study of the connections of the STG with medial paralimbic cortex showed that the caudal part of the STG (area Tpt and caudal area paAlt) and adjacent cortex of the upper bank of the superior temporal sulcus (caudal area TPO) have reciprocal connections with the caudal cingulate gyrus (areas 23a, b and c), retrosplenial cortex (area 30), and area 31. By contrast, cortex of the rostral-to-mid STG (areas Ts2, Ts3, and the rostral part of area paAlt) and adjacent upper bank of the STS (mid-area TPO) have few, if any, such interconnections. It is suggested that this connectional pattern of the caudal STG is consistent with its putative role of localizing sounds in space as proposed in recent studies. C1 [Seltzer, Benjamin] Harvard Univ, Sch Med, Dept Neurol, VA Boston Healthcare Syst, Boston, MA 02130 USA. [Seltzer, Benjamin] Tulane Univ, Sch Med, Dept Psychiat & Neurol, New Orleans, LA 70112 USA. [Pandya, Deepak N.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Sch Med, Boston, MA 02215 USA. [Pandya, Deepak N.] ENRM Vet Hosp, Bedford, MA USA. [Pandya, Deepak N.] Boston Univ, Dept Anat & Neurobiol, Boston, MA 02215 USA. RP Seltzer, B (reprint author), Harvard Univ, Sch Med, Dept Neurol, VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM bseltzer@partners.org FU ENRM Veterans Hospital, Bedford, MA; Boston and Southeast Louisiana VA Healthcare Systems FX We thank Dr. Don Siwek, Dr. Douglas L. Rosene, and Mr. Jason MacMore for help with the figures and photographs. This study was supported by the ENRM Veterans Hospital, Bedford, MA, and the Boston and Southeast Louisiana VA Healthcare Systems. NR 68 TC 11 Z9 12 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 2009 VL 195 IS 2 BP 325 EP 334 DI 10.1007/s00221-009-1795-4 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 439TL UT WOS:000265649800014 PM 19381619 ER PT J AU Jin, G Tsuji, K Xing, CH Yang, YG Wang, XY Lo, EH AF Jin, Guang Tsuji, Kiyoshi Xing, Changhong Yang, Yong-Guang Wang, Xiaoying Lo, Eng H. TI CD47 gene knockout protects against transient focal cerebral ischemia in mice SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Neuroprotection; Stroke; Blood-brain barrier; Neuroinflammation; MMP-9; Brain edema ID MATRIX-METALLOPROTEINASE; NEUTROPHIL ACCUMULATION; MIGRATION; STROKE; EXPRESSION; INJURY; THROMBOSPONDIN-1; INFLAMMATION; DISRUPTION; RAT AB CD47 is a cell surface glycoprotein that helps mediate neutrophil transmigration across blood vessels. The present Study was performed to determine whether absence of the CD47 gene decreases focal ischemic brain damage. Mice were subjected to 90 min middle cerebral artery occlusion. CD47 knockout mice were compared against matching wildtype mice. CD47 expression was checked by Western blotting. Infarct volume and ischemic brain swelling were quantified with cresyl violet-stained brain sections at 24 and 72 h after ischemia. The tight junction protein claudin-5 was detected by imunohistochemistry. Two surrogate markers of neuroinflammation, brain levels of matrix metalloproteinase-9 (MMP-9) and infiltration of neutrophils, were assessed by immunohistochemistry. Western blots confirmed that CD47 was absent in knockout brains. Ischemia did not appear to upregulate total brain levels of CD47 in WT mice. In CD47 knockout mice, infarct volumes were reduced at 24 and 72 h after ischemia, and hemispheric swelling was decreased at 72 h. Loss of claudin-5 was observed in ischemic WT brain. This effect was ameliorated in CD47 knockout brains. Extravasation of neutrophils into the brain parenchyma was significantly reduced in CD47 knockout mice Compared to wildtype mice. MMP-9 appeared to be upregulated in microvessels within ischemic brain. MMP-9 levels were markedly lower in CD47 knockout brains compared to wildtype brains. We conclude that CD47 is broadly involved in neuroinflammation, and this integrin-associated-protein plays a role in promoting MMP-9 upregulaton, neutrophil extravasation, brain swelling and progression of acute ischemic brain injury. (C) 2009 Elsevier Inc. All rights reserved. C1 [Jin, Guang; Tsuji, Kiyoshi; Xing, Changhong; Wang, Xiaoying; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol & Neurol,Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Xing, Changhong] Capital Med Univ, Xuan Wu Hosp, Beijing, Peoples R China. [Yang, Yong-Guang] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Transplantat Biol Res Ctr, Charlestown, MA 02129 USA. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol & Neurol,Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA. EM lo@helix.mgh.harvard.edu FU NIH [R01-NS37074, R01-NS48422, R01-NS53560, P01-NS55104] FX Supported in part by NIH grants R01-NS37074, R01-NS48422, R01-NS53560, and P01-NS55104. NR 32 TC 31 Z9 32 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2009 VL 217 IS 1 BP 165 EP 170 DI 10.1016/j.expneurol.2009.02.004 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 442RT UT WOS:000265859000019 PM 19233173 ER PT J AU Lu, JM Wang, XW Marin-Muller, C Wang, H Lin, PH Yao, QZ Chen, CY AF Lue, Jian-Ming Wang, Xinwen Marin-Muller, Christian Wang, Hao Lin, Peter H. Yao, Qizhi Chen, Changyi TI Current advances in research and clinical applications of PLGA-based nanotechnology SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE cancer; cardiovascular disease; diagnosis; drug delivery; imaging; nanoparticle; nanotechnology; polylactic-co-glycolic acid; vaccine ID POLY(LACTIC-CO-GLYCOLIC ACID) NANOPARTICLES; REPEAT PERCUTANEOUS INTERVENTION; PORCINE CORONARY-ARTERIES; MUSCLE-CELL PROLIFERATION; TARGETED DRUG-DELIVERY; IN-STENT RESTENOSIS; CONTRAST AGENT; BIODEGRADABLE NANOPARTICLES; CONTROLLED-RELEASE; DENDRITIC CELLS AB Co-polymer poly(lactic-co-glycolic acid) (PLGA) nanotechnology has been developed for many years and has been approved by the US FDA for the use of drug delivery, diagnostics and other applications of clinical and basic science research, including cardiovascular disease, cancer, vaccine and tissue engineering. This article presents the more recent successes of applying PLGA-based nanotechnologies and tools in these medicine-related applications. It focuses on the possible mechanisms, diagnosis and treatment effects of PLGA preparations and devices. This updated information will benefit to both new and established research scientists and clinical physicians who are interested in the development and application of PLGA nanotechnology as new therapeutic and diagnostic strategies for many diseases. C1 [Chen, Changyi] Baylor Coll Med, Michael E DeBakey Dept Surg R413, Houston, TX 77030 USA. [Lue, Jian-Ming; Wang, Xinwen; Marin-Muller, Christian; Wang, Hao; Lin, Peter H.; Yao, Qizhi] Baylor Coll Med, Michael E DeBakey Dept Surg, Mol Surgeon Res Ctr, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. [Lue, Jian-Ming; Wang, Xinwen; Marin-Muller, Christian; Wang, Hao; Lin, Peter H.; Yao, Qizhi] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Chen, CY (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg R413, 1 Baylor Plaza,Mail Stop BCM390, Houston, TX 77030 USA. EM jchen@bcm.tmc.edu FU NIBIB NIH HHS [R01 EB002436, R01 EB002436-04, EB002436] NR 141 TC 277 Z9 291 U1 14 U2 100 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2009 VL 9 IS 4 BP 325 EP 341 DI 10.1586/ERM.09.15 PG 17 WC Pathology SC Pathology GA 446SC UT WOS:000266140400005 PM 19435455 ER PT J AU Quinn, JF Crane, S Harris, C Wadsworth, TL AF Quinn, Joseph F. Crane, Susanne Harris, Christopher Wadsworth, Teri L. TI Copper in Alzheimer's disease: too much or too little? SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE Alzheimer's disease; animal model; chelation; clinical trial; copper; oxidative damage AB A considerable amount of literature has accrued examining the role of copper in the pathogenesis of Alzheimer's disease. Remarkably, there is in vitro and animal data to support both copper toxicity and copper deficiency as relevant mechanisms in Alzheimer's disease. These data have prompted preliminary clinical trials of both copper complexing therapy and copper supplementation therapy, which have yielded mixed results. The preclinical and clinical studies are discussed here in an effort to determine how to move forward with rational clinical trials focused on copper modulation. C1 [Quinn, Joseph F.; Crane, Susanne; Harris, Christopher; Wadsworth, Teri L.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Neurol CR 131, Portland, OR 97239 USA. RP Quinn, JF (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Neurol CR 131, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM quinnj@ohsu.edu FU NIA [R21AG027445A]; Department of Veteran's Affairs FX This work was supported by NIA (R21AG027445A) and the Department of Veteran's Affairs. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 54 TC 26 Z9 27 U1 1 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 EI 1744-8360 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD MAY PY 2009 VL 9 IS 5 BP 631 EP 637 DI 10.1586/ERN.09.27 PG 7 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA V39ZQ UT WOS:000209449300011 PM 19402774 ER PT J AU Borrero, S Schwarz, EB Reeves, MF Bost, JE Creinin, MD Ibrahim, SA AF Borrero, Sonya Schwarz, Eleanor B. Reeves, Matthew F. Bost, James E. Creinin, Mitchell D. Ibrahim, Said A. TI Does vasectomy explain the difference in tubal sterilization rates between black and white women? SO FERTILITY AND STERILITY LA English DT Article DE National Survey of Family Growth (NSFG); race/ethnicity; tubal sterilization; vasectomy ID UNITED-STATES; CONTRACEPTIVE STERILIZATION AB Objective: To examine whether the observed difference in tubal sterilization rates between black and white women is dependent on racial/ethnic differences in vasectomy rates. Design: Secondary analysis of national, cross-sectional survey. Setting: 2002 National Survey of Family Growth. Patient(s): Women 15 to 44 years old with a current partner who were able to provide information about their partner's vasectomy status. Intervention(s): None. Main Outcome Measure(s): The primary outcome was tubal sterilization. Among women with a current partner who had not undergone vasectomy, a multivariable logistic regession model was used to estimate the effects of race/ethnicity on tubal sterilization after adjusting for potential confounders. Result(s): Of the 3,391 women in the sample, 14% of white women had a current partner who had undergone vasectomy compared with 5% of Hispanic women and 4% of black women. Among the 3.064 women whose partners had not undergone vasectomy, black women were more likely to undergo tubal sterilization (odds ratio: 1.6; 95% confidence interval: 1.1, 2.2) on the basis of adjusted multivariable analysis. Conclusion(s): After controlling for partner vasectomy status, black women were still more likely to undergo tubal sterilization than white women. (Fertil Steril (R) 2009;91:1642-5. (C)2009 by American Society for Reproductive Medicine.) C1 [Borrero, Sonya] Univ Pittsburgh, Ctr Res Hlth Care, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. [Borrero, Sonya; Ibrahim, Said A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ & Promot, Pittsburgh, PA USA. [Schwarz, Eleanor B.; Reeves, Matthew F.; Creinin, Mitchell D.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Bost, James E.] Univ Pittsburgh, Sch Med, Inst Clin Res Educ, Pittsburgh, PA USA. [Creinin, Mitchell D.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP Borrero, S (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, Sch Med, Div Gen Internal Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15260 USA. EM borrerosp@upmc.edu RI Potter, Joseph/A-3122-2008; OI Reeves, Matthew/0000-0001-7749-7447; Schwarz, Eleanor Bimla/0000-0002-9912-8236 FU Organon; Bayer FX M.D.C. has received research funding from, and served as a consultant for, Organon, and has received research funding and honoraria from Bayer. S.A.I. has nothing to disclose. NR 12 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2009 VL 91 IS 5 BP 1642 EP 1645 DI 10.1016/j.fertnstert.2008.01.103 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 444GR UT WOS:000265969200004 PM 18394618 ER PT J AU Souter, I Huang, A Martinez-Maza, O Breen, EC Decherney, AH Chaudhuri, G Nathan, L AF Souter, Irene Huang, Andy Martinez-Maza, Otoniel Breen, Elizabeth Crabb Decherney, Alan H. Chaudhuri, Gautam Nathan, Lauren TI Serum levels of soluble vascular cell adhesion molecule-1, tumor necrosis factor-alpha, and interleukin-6 in in vitro fertilization cycles SO FERTILITY AND STERILITY LA English DT Article DE Soluble vascular adhesion molecule-1; tumor necrosis factor-alpha; interleukin-6; E-2; in vitro fertilization ID HORMONE REPLACEMENT THERAPY; C-REACTIVE PROTEIN; OVARIAN HYPERSTIMULATION SYNDROME; CORONARY-ARTERY-DISEASE; HUMAN ENDOTHELIAL-CELLS; POSTMENOPAUSAL WOMEN; LEUKOCYTE ADHESION; POLYCYSTIC OVARIES; ESTROGEN-RECEPTOR; FOLLICULAR-FLUID AB Objective: To assess whether gonadotropin-induced changes in E-2 alter serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and proinflammatory cytokines. Design: Prospective collection of serum in patients undergoing WE Setting: University hospital. Patient(s): Twenty-four infertile women. Intervention(s): Serum collection at baseline, in the mid and late follicular phases, at oocyte retrieval, and in the mid and late luteal phases. Main Outcome Measure(s): Samples were assayed for sVCAM-1, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and E-2. Result(s): The VCAM-1 was maximally suppressed in the luteal phase. Luteal sVCAM-1 levels correlated [1] positively with the patient's age, units of gonadotropins, day 3 FSH levels and [2] negatively with [a] the follicular, retrieval, and luteal E-2 levels and [b] the number of preovulatory follicles and oocytes retrieved. Similar correlations were noted in the late luteal phase. Serum TNF-alpha reached a peak in the mid-follicular phase and a nadir in the luteal phase, The TNF-alpha levels at retrieval correlated [1] positively with the patient's age and [2] negatively with E-2 and number of preovulatory follicles and retrieved oocytes. The IL-6 levels were suppressed in the follicular phase and correlated negatively with E-2 levels. Conclusion(s): Changes in E-2 levels seen during gonadotropin stimulation significantly alter VCAM-1 expression and induce changes in serum IL-6 and TNF-alpha levels. (Fertil Steril (R) 2009;91:2012-9. (C)2009 by American Society for Reproductive Medicine.) C1 [Souter, Irene; Huang, Andy; Martinez-Maza, Otoniel; Breen, Elizabeth Crabb; Decherney, Alan H.; Chaudhuri, Gautam; Nathan, Lauren] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Chaudhuri, Gautam] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Souter, I (reprint author), Massachusetts Gen Hosp, Fertil Ctr, 55 Fruit St Yawkey 10A, Boston, MA 02114 USA. EM isouter@partners.org RI Martinez-Maza, Otoniel/B-2667-2009 OI Martinez-Maza, Otoniel/0000-0003-1364-0675 NR 75 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2009 VL 91 IS 5 SU S BP 2012 EP 2019 DI 10.1016/j.fertnstert.2008.04.039 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 444GS UT WOS:000265969300007 PM 18778820 ER EF