FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Thomas, DS Antony, S Stephen, AJ Marchand, C Njar, VC Pommier, Y AF Thomas, Dexheimer S. Antony, Smitha Stephen, Andrew J. Marchand, Christophe Njar, Vincent C. Pommier, Yves TI Discovery and biochemical characterization of tyrosyl-DNA phosphodiesterase I inhibitors SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Thomas, Dexheimer S.; Antony, Smitha; Marchand, Christophe; Pommier, Yves] NCI, NIH, CCR, Bethesda, MD USA. [Stephen, Andrew J.] NCI, Frederick, MD USA. [Njar, Vincent C.] Univ Maryland, Sch Med, Baltimore, MD USA. RI Marchand, Christophe/D-8559-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3502S EP 3502S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000513 ER PT J AU Ross, RW Srinivasan, R Vaishampayan, U Bukowski, R Rosenberg, J Eisenberg, P Logan, T Srinivas, S Stein, M Mueller, T Keer, HN AF Ross, Robert W. Srinivasan, Ramaprasad Vaishampayan, Ulka Bukowski, Ronald Rosenberg, Jonathan Eisenberg, Peter Logan, Theodore Srinivas, Sandhya Stein, Mark Mueller, Thomas Keer, Harold N. TI A Phase 2 study of the dual MET/VEGFR2 inhibitor XL880 in patients (pts) with papillary renal carcinoma (PRC) SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Ross, Robert W.] Dana Farber Canc Inst, Boston, MA USA. [Srinivasan, Ramaprasad] Natl Canc Inst, Urol Oncol Branch, Bethesda, MD USA. [Vaishampayan, Ulka] Karmanos Canc Ctr, Detroit, MI USA. [Bukowski, Ronald] Cleveland Clin, Cleveland, OH USA. [Rosenberg, Jonathan] Univ Calif San Francisco, San Francisco, CA USA. [Eisenberg, Peter] California Canc Ctr, Greenbrae, CA USA. [Logan, Theodore] Indiana Univ, Ctr Canc, Indianapolis, IN USA. [Srinivas, Sandhya] Stanford Univ, Ctr Canc, Stanford, CA 94305 USA. [Stein, Mark] Inst Canc Res, New Brunswick, NJ USA. [Mueller, Thomas; Keer, Harold N.] Exelixis Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3511S EP 3511S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000541 ER PT J AU Min, C Liebes, L Brooks, P Yoon, J Yee, H Hamilton, A Buckley, M Wright, J Osman, I Muggia, F Pavlick, AC AF Min, Christina Liebes, Leonard Brooks, Peter Yoon, Joanne Yee, Herman Hamilton, Anne Buckley, Michael Wright, John Osman, Iman Muggia, Franco Pavlick, Anna C. TI Phase II trial of BAY 43-9006 (sorafenib-BAY) in metastatic melanoma (MM) including detection of BRAF mutations with mutant specific-PCIR (MIS-PCR) and altered proliferation pathways SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Min, Christina; Liebes, Leonard; Brooks, Peter; Yoon, Joanne; Yee, Herman; Buckley, Michael; Osman, Iman; Muggia, Franco; Pavlick, Anna C.] NYU, Inst Canc, New York, NY USA. [Hamilton, Anne] Sydney Canc Ctr, Sydney, NSW, Australia. [Wright, John] NCI, CTEP, Bethesda, MD 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3512S EP 3513S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000546 ER PT J AU Matulonis, U Berlin, S Krasner, C Tyburski, K Lee, J Roche, M Ivy, P Penson, R AF Matulonis, Ursula Berlin, Suzanne Krasner, Carolyn Tyburski, Karin Lee, Julie Roche, Maria Ivy, Percy Penson, Richard TI Phase II study of cediranib (RECENTIN (TM), AZD2171) in recurrent epithelial ovarian cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Matulonis, Ursula; Berlin, Suzanne; Tyburski, Karin; Lee, Julie] Dana Farber Canc Inst, Boston, MA USA. [Krasner, Carolyn; Roche, Maria; Penson, Richard] Massachusetts Gen Hosp, Boston, MA USA. [Ivy, Percy] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3515S EP 3515S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000554 ER PT J AU Anchoori, RK Kortenhorst, MSQ Jimeno, A Sarkar, T Hallur, G Van Diest, RJ Hidalgo, M Hamel, E Khan, SR AF Anchoori, Ravi K. Kortenhorst, Madeleine S. Q. Jimeno, Antonio Sarkar, Taradas Hallur, Gurulingappa Van Diest, R. J. Hidalgo, Manuel Hamel, Ernest Khan, Saeed R. TI Design, synthesis and evaluation of microtubule inhibitors phenoxy pyridine (PIP) and phenyl sulfanyl pyridine (PSP) analogs for cancer therapy SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Anchoori, Ravi K.; Jimeno, Antonio; Hallur, Gurulingappa; Hidalgo, Manuel; Khan, Saeed R.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Kortenhorst, Madeleine S. Q.; Van Diest, R. J.] Dept Med Oncol, Utrecht, Netherlands. [Sarkar, Taradas; Hamel, Ernest] Natl Canc Inst, Frederick, MD 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3520S EP 3520S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000568 ER PT J AU Nikolovska-Coleska, Z Meagher, JL Yang, CY Jiang, S Qiu, S Stuckey, J Roller, PP Wang, S AF Nikolovska-Coleska, Zaneta Meagher, Jennifer L. Yang, Chao-Yie Jiang, Sheng Qiu, Su Stuckey, Jeanne Roller, Peter P. Wang, Shaomeng TI Design of cyclic Smac mimetic peptide and in vitro characterization of its complex with X-linked inhibitor of apoptosis protein (XIAP) SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Nikolovska-Coleska, Zaneta; Yang, Chao-Yie; Qiu, Su; Wang, Shaomeng] Univ Michigan, Ctr Comprehens Canc, Dept Internal Med Pharmacol Med Chem, Ann Arbor, MI 48109 USA. [Meagher, Jennifer L.; Stuckey, Jeanne] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Jiang, Sheng; Roller, Peter P.] Natl Canc Inst, Med Chem Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3524S EP 3524S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000579 ER PT J AU Hollingshead, MG Borgel, SD Carter, J Bonomi, CA Divelbiss, R Stotler, H Dougherty, K Greenberg, N Kaur, G Pommier, Y Monks, PA Parchment, R Kinders, R Tomaszewski, JE Doroshow, JH AF Hollingshead, Melinda G. Borgel, Suzanne D. Carter, John Bonomi, Carrie A. Divelbiss, Raymond Stotler, Howard Dougherty, Kelly Greenberg, Nathaniel Kaur, Gurmeet Pommier, Yves Monks, P. Anne Parchment, Ralph Kinders, Robert Tomaszewski, Joseph E. Doroshow, James H. TI Evidence of in vivo efficacy for the indenoisoquinolines linked with pharmacodynamic markers for gamma H2AX. SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Hollingshead, Melinda G.; Greenberg, Nathaniel; Kaur, Gurmeet; Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diagnosis, Bethesda, MD USA. [Borgel, Suzanne D.; Carter, John; Bonomi, Carrie A.; Divelbiss, Raymond; Stotler, Howard; Dougherty, Kelly; Monks, P. Anne; Parchment, Ralph; Kinders, Robert] SAIC Frederick, Frederick, MD USA. [Pommier, Yves] NCI, Ctr Canc Res, Bethesda, MD USA. 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3532S EP 3532S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000604 ER PT J AU Elser, C Tsao, M Pond, G Chen, EX Spohn, J Agulnik, M Cohen, EE Cohen, RB Dancy, J Siu, LL AF Elser, C. Tsao, M. Pond, G. Chen, E. X. Spohn, J. Agulnik, M. Cohen, E. E. Cohen, R. B. Dancy, J. Siu, L. L. TI Fluororescence in situ hybridization (FISH) gene amplification analysis of EGFR and HER2 in patients with malignant salivary gland tumors (MSGT) treated with lapatinib SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Elser, C.; Tsao, M.; Pond, G.; Chen, E. X.; Agulnik, M.; Cohen, R. B.; Siu, L. L.] Princess Margaret Hosp, Phase II Consutium, Toronto, ON, Canada. [Spohn, J.] Target Mol Diagnostics, Westmont, IL USA. [Cohen, R. B.] Univ Chicago, Chicago, IL 60637 USA. [Dancy, J.] NCI, 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3539S EP 3539S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000627 ER PT J AU Ji, J Yutzy, W Putvatana, R Zhang, Y Kinders, RJ Parchment, RE Hollingshead, MG Tomaszewski, JE Doroshow, JH AF Ji, Jay Yutzy, Will Putvatana, Ravithat Zhang, Yiping Kinders, Robert J. Parchment, Ralph E. Hollingshead, Melinda G. Tomaszewski, Joseph E. Doroshow, James H. CA NCI Phase 0 Team TI Phosphorylated histone H2Ax in PBMCs as a pharmacodynamic surrogate response to DNA damage by topoisomerase I inhibitors SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Ji, Jay; Yutzy, Will; Putvatana, Ravithat; Zhang, Yiping; Kinders, Robert J.; Parchment, Ralph E.] SAIC Frederick Inc, NCI, Frederick, MD USA. [Hollingshead, Melinda G.; Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diagnos, Bethesda, MD USA. [NCI Phase 0 Team] NCI, Ctr Canc Res, Bethesda, MD USA. 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3542S EP 3542S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000635 ER PT J AU Kinders, RJ Hollingshead, MG Lawrence, S Ji, JJ Tomaszewski, JE Doroshow, JH Parchment, RE AF Kinders, Robert J. Hollingshead, Melinda G. Lawrence, Scott Ji, Jay Jiuping Tomaszewski, Joseph E. Doroshow, James H. Parchment, Ralph E. CA NCI Phase 0 Team TI Development and validation of a quantitative assay for H2AX in needle biopsies using topoisomerase I inhibitors SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Kinders, Robert J.; Lawrence, Scott; Ji, Jay Jiuping; Parchment, Ralph E.] SAIC Frederick Inc, NCI, Frederick, MD USA. [Hollingshead, Melinda G.; Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diagnos, Bethesda, MD USA. [NCI Phase 0 Team] NCI, Ctr Canc Res, Bethesda, MD USA. 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3542S EP 3542S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000636 ER PT J AU Sasiela, C Stewart, D Safiran, Y Kitagaki, J Yang, Y Weissman, A Oberoi, P Davydov, I Goncharova, E Beutler, J O'Keefe, B McMahon, J AF Sasiela, Christy Stewart, David Safiran, Yassamin Kitagaki, Jirouta Yang, Yili Weissman, Allan Oberoi, Pankaj Davydov, Ilia Goncharova, Ekaterina Beutler, John O'Keefe, Barry McMahon, James TI Identification of inhibitors for MDM2 ubiquitin ligase activity from natural products by a novel high throughput electrochemiluminescent screen SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Sasiela, Christy; Kitagaki, Jirouta; Yang, Yili; Weissman, Allan; Goncharova, Ekaterina; Beutler, John; O'Keefe, Barry; McMahon, James] Natl Canc Inst, Frederick, MD USA. [Stewart, David; Safiran, Yassamin; Oberoi, Pankaj; Davydov, Ilia] Meso Scale Discovery, Gaithersburg, MD USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3544S EP 3544S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000641 ER PT J AU Zhang, YW Hamel, E Ghosh, AK Pommier, Y AF Zhang, Yong-Wei Hamel, Ernest Ghosh, Arun K. Pommier, Yves TI The marine compound Lasonolide A is a potent inducer of premature chromosome condensation and inhibitor of cell adhesion SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Zhang, Yong-Wei; Pommier, Yves] NIH, Natl Canc Inst, Mol Pharmacol Lab, Bethesda, MD USA. [Hamel, Ernest] NIH, Natl Canc Inst, Screening Technol Branch, Frederick, MD USA. [Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3544S EP 3544S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000643 ER PT J AU Paoloni, M Mazcko, C Currier, D Kisseberth, W Fan, T Lana, S Vail, D Khanna, C AF Paoloni, Melissa Mazcko, Christina Currier, Duane Kisseberth, William Fan, Timothy Lana, Susan Vail, David Khanna, Chand TI Evaluation of the mTOT inhibitor, rapamycin in dogs with spontaneously derived osteosarcoma: A focus on preclinical pharmacokinetics and pharmacodynamics SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Paoloni, Melissa; Mazcko, Christina; Currier, Duane; Khanna, Chand] NCI, NIH, Bethesda, MD USA. [Kisseberth, William] Ohio State Univ, Columbus, OH 43210 USA. [Fan, Timothy] Univ Illinois, Urbana, IL USA. [Lana, Susan] Colorado State Univ, Ft Collins, CO USA. [Vail, David] Univ Wisconsin, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3554S EP 3555S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000672 ER PT J AU Sissung, TM Danesi, R Price, DK Steinberg, SM de Wits, R Compton, K Zahid, M Gaikwad, N Cavalieri, E Dahut, WL Sackett, DL Figg, WD Sparreboom, A AF Sissung, Tristan M. Danesi, Romano Price, Douglas K. Steinberg, Seth M. de Wits, Ronald Compton, Kathryn Zahid, Muhammad Gaikwad, Nilesh Cavalieri, Ercole Dahut, William L. Sackett, Dan L. Figg, William D., Sr. Sparreboom, Alex TI Association of the CYP1B1*3 allele with survival in patients with prostate cancer receiving docetaxel SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Sissung, Tristan M.; Sparreboom, Alex] Ctr Canc Res, NCI, Clin Pharmacol Program, Bethesda, MD USA. [Danesi, Romano] Univ Pisa, Dept Oncol, Transplant & Adv Technol Med, I-56100 Pisa, Italy. [Price, Douglas K.] Ctr Canc Res, NCI, Mol Pharmacol Sect, Bethesda, MD USA. [Steinberg, Seth M.] Ctr Canc Res, NCI, Biostat & Data Management, Bethesda, MD USA. [de Wits, Ronald] Erasmus MC, Dr Daniel Den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. [Compton, Kathryn] SAIC Frederick Inc, NCI Frederick, Frederick, MD USA. [Zahid, Muhammad; Gaikwad, Nilesh; Cavalieri, Ercole] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE USA. [Dahut, William L.; Sparreboom, Alex] Ctr Canc Res, NCI, Med Oncol Branch, Bethesda, MD USA. [Sackett, Dan L.] NICHHD, Lab Integrat & Med Biophys, Bethesda, MD USA. RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3568S EP 3568S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000710 ER PT J AU Patel, JB Sullivan, P Zhang, K Zhang, SL Mock, BA AF Patel, Jyoti B. Sullivan, Patrick Zhang, Ke Zhang, Shuling Mock, Beverly A. TI Combined use of HDAC and mTOR inhibitors has synergistic effect on inhibiting B-cell tumor cell lines SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Patel, Jyoti B.; Sullivan, Patrick; Zhang, Ke; Zhang, Shuling; Mock, Beverly A.] NCI, NIH, 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3571S EP 3572S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000720 ER PT J AU Jain, L Gardner, ER Aragon-Ching, JB Compton, K Venitz, J Wright, JJ Dahut, WL Figg, WD AF Jain, Lokesh Gardner, Erin R. Aragon-Ching, Jeanny B. Compton, Kathryn Venitz, Jurgen Wright, John J. Dahut, William L. Figg, William D. TI A phase II clinical trial of sorafenib in androgen-independent prostate cancer: Characterization of pharmacokinetics SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Jain, Lokesh; Venitz, Jurgen] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Gardner, Erin R.; Compton, Kathryn] SAIC Frederick Inc, NCI, Frederick, MD USA. [Aragon-Ching, Jeanny B.; Wright, John J.; Dahut, William L.; Figg, William D.] Natl Canc Inst, Bethesda, MD USA. RI Figg Sr, William/M-2411-2016 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3576S EP 3576S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000733 ER PT J AU Liu, X Maurer, BJ Frgala, T Page, JG Noker, PE Fulton, R Ames, MM Reid, JM Gupta, S Vishnuvaijala, R Tomaszewski, JE Schweikart, K Reynolds, CP AF Liu, Xinli Maurer, Barry J. Frgala, Tomas Page, John G. Noker, Patricia E. Fulton, Ronna Ames, Matthew M. Reid, Joel M. Gupta, Shanker Vishnuvaijala, Rao Tomaszewski, Joseph E. Schweikart, Karen Reynolds, C. Patrick TI Preclinical toxicology and pharmacokinetics of intravenous lipid emulsion fenretinide SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Liu, Xinli; Maurer, Barry J.; Frgala, Tomas; Reynolds, C. Patrick] Univ So Calif, Childrens Hosp Los Angeles, Inst Pediat Clin Res, Dev Therapeut Program, Los Angeles, CA USA. [Page, John G.; Noker, Patricia E.; Fulton, Ronna] So Res Inst, Birmingham, AL USA. [Ames, Matthew M.; Reid, Joel M.] Mayo Clin, Rochester, MN USA. [Gupta, Shanker; Vishnuvaijala, Rao; Tomaszewski, Joseph E.; Schweikart, Karen] Natl Canc Inst, Frederick, MD 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3578S EP 3579S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000740 ER PT J AU Takimoto, CH Chu, QSC Yen, Y O'Rourke, P Cooper, J Pardo, S Tolcher, AW Patnaik, A Papadopoulos, K Beeram, M Ricart, AD Lin, CC Mita, AC Calvo, E Espinoza-Delgado, I Zwiebel, J Sarantopoulos, J AF Takimoto, Chris H. Chu, Quincy S-C Yen, Yun O'Rourke, Patricia Cooper, Joshua Pardo, Sam Tolcher, Anthony W. Patnaik, Amita Papadopoulos, Kyriakos Beeram, Muralidhar Ricart, Alejandro D. Lin, Chia-Chi Mita, Alain C. Calvo, Emiliano Espinoza-Delgado, Igor Zwiebel, Jamie Sarantopoulos, John TI A Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of GT12040 (GTI), a novel ribonucleotide reductase inhibitor in combination with gemcitabine (Gem) in adult patients (pts) with advanced solid tumors SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Takimoto, Chris H.; Tolcher, Anthony W.; Patnaik, Amita; Papadopoulos, Kyriakos] S Texas Accelerated Res Therapeut, San Antonio, TX USA. [Chu, Quincy S-C; O'Rourke, Patricia; Cooper, Joshua; Pardo, Sam; Ricart, Alejandro D.; Lin, Chia-Chi; Mita, Alain C.; Calvo, Emiliano; Sarantopoulos, John] Canc Therapy & Res Ctr S Texas, San Antonio, TX USA. [Yen, Yun] City Hope Canc Ctr, Duarte, CA USA. [Beeram, Muralidhar] Univ Texas Hlth Sci Ctr, San Antonio, TX USA. [Espinoza-Delgado, Igor; Zwiebel, Jamie] Natl Canc Inst, Bethesda, MD 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3579S EP 3579S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000741 ER PT J AU Giaccone, G Zatloukal, P Roubec, J Musil, J Kuta, M van Klaveren, RJ Chaudhary, S Gunther, A Shamsili, S Kazei, D Verbeeck, F AF Giaccone, Giuseppe Zatloukal, Petr Roubec, Jaromir Musil, Jaromir Kuta, Milan van Klaveren, R. J. Chaudhary, Subhash Gunther, Adrie Shamsili, Setareh Kazei, Dmitri Verbeeck, Frank TI A phase II, monotherapy study of YM155, a novel survivin suppressant, in previously treated advanced stage non-small cell lung cancer (NSCLC) SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Giaccone, Giuseppe] Natl Canc Inst, Bethesda, MD USA. [Zatloukal, Petr] FN Bulovka, Prague, Czech Republic. [Roubec, Jaromir] FN Ostrava Poruba, Ostrava, Czech Republic. [Musil, Jaromir] FN Motole, Prague, Czech Republic. [Kuta, Milan] Nemocnice Chomutuv, Chomutov, Czech Republic. [van Klaveren, R. J.] Erasmus MC, Rotterdam, Netherlands. [Chaudhary, Subhash] Onkol Cent JG Mendla, Novy Jicin, Czech Republic. [Gunther, Adrie; Shamsili, Setareh; Kazei, Dmitri; Verbeeck, Frank] Astellas Pharma Europe BV, Leiderdorp, Netherlands. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3597S EP 3597S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000796 ER PT J AU Pommier, YG Antony, S Agama, K Miao, ZH Takagi, K Bates, S Wright, MH Robbles, AI Varticovski, L Nagarajan, M Morre, A Cushman, M AF Pommier, Yves G. Antony, Smitha Agama, Keli Miao, Ze-Hong Takagi, Kazutaka Bates, Susan Wright, Mollie H. Robbles, Anna I. Varticovski, Lyuba Nagarajan, Muthukaman Morre, Andrew Cushman, Mark TI Novel indenoisoquinolines NSC 725776 and NSC 724998 produce persistent topoisomerase I cleavage complexes and overcome multidrug resistance SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Pommier, Yves G.; Antony, Smitha; Agama, Keli; Miao, Ze-Hong; Takagi, Kazutaka; Bates, Susan; Wright, Mollie H.; Robbles, Anna I.; Varticovski, Lyuba] NCI, CCR, Bethesda, MD USA. [Nagarajan, Muthukaman; Morre, Andrew; Cushman, Mark] Purdue Univ, W Lafayette, IN 47907 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3598S EP 3598S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000798 ER PT J AU Houghton, PJ Maris, JM Courtright, J Friedman, H Keir, ST Lock, RB Carol, H Gorlick, R Kolb, EA Keshelava, N Reynolds, P Morton, CL Smith, MA AF Houghton, Peter J. Maris, John M. Courtright, Joshua Friedman, Henry Keir, Stephen T. Lock, Richard B. Carol, Hernan Gorlick, Richard Kolb, E. Anders Keshelava, Nino Reynolds, Patrick Morton, Christopher L. Smith, Malcolm A. TI Initial testing of the histone deacetylase inhibitor Vorinostat by the Pediatric Preclinical Testing Program SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Houghton, Peter J.; Morton, Christopher L.] St Jude Childrens Hosp, Memphis, TN USA. [Maris, John M.; Courtright, Joshua] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Friedman, Henry; Keir, Stephen T.] Duke Univ, Durham, NC 27706 USA. [Lock, Richard B.; Carol, Hernan] Childrens Canc Res Inst, Sydney, NSW, Australia. [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Keshelava, Nino; Reynolds, Patrick] Childrens Hosp Los Angeles, Los Angeles, CA USA. [Smith, Malcolm A.] CTEP, NCI, Bethesda, MD USA. RI Carol, Hernan/F-5750-2013 OI Carol, Hernan/0000-0002-9443-8032 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3600S EP 3601S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000805 ER PT J AU Kim, YS Lee, MJ Janik, JE Morris, JC Chung, EJ Lee, S Kajiguchi, T Pise-Masison, C O'Mahony, D Waldmann, TA Brady, JN Trepel, JB AF Kim, Yeong Sang Lee, Min-Jung Janik, John E. Morris, John C. Chung, Eun Joo Lee, Sunmin Kajiguchi, Tomohiro Pise-Masison, Cynthia O'Mahony, Deirdre Waldmann, Thomas A. Brady, John N. Trepel, Jane B. TI Beta-catenin signaling regulates acute adult T-cell leukemia/lymphoma SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Kim, Yeong Sang; Lee, Min-Jung; Chung, Eun Joo; Lee, Sunmin; Trepel, Jane B.] NIH, NCI, Med Oncol Branch, Bethesda, MD USA. [Janik, John E.; Morris, John C.; O'Mahony, Deirdre; Waldmann, Thomas A.] NIH, NCI, Metab Branch, Bethesda, MD USA. [Kajiguchi, Tomohiro] NIH, NCI, Urol Oncol Branch, Bethesda, MD USA. [Pise-Masison, Cynthia; Brady, John N.] NIH, NCI, Cellular Oncol Lab, Bethesda, MD 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3609S EP 3609S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000832 ER PT J AU Karmely, M Rubinstein, DB Wreschner, DH AF Karmely, Maya Rubinstein, Daniel B. Wreschner, Daniel H. TI Immunotoxins against a non-tandem repeat epitope on the membrane bound MUC1 kill tumor cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Karmely, Maya; Wreschner, Daniel H.] Tel Aviv Univ, Ramat Aviv, Israel. [Rubinstein, Daniel B.] Natl Canc Inst, Bethesda, MD USA. NR 1 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3612S EP 3613S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000844 ER PT J AU Staudt, LM AF Staudt, Louis M. TI Achilles heel RNA interference screens for molecular targets in cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Staudt, Louis M.] Natl Canc Inst, Bethesda, MD USA. 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3622S EP 3623S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000874 ER PT J AU Neckers, LM AF Neckers, Leonard M. TI Regulation of Hsp90 chaperone activity by acetylation SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Neckers, Leonard M.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3626S EP 3626S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000882 ER PT J AU Dhasarathy, A Kajita, M Wade, PA AF Dhasarathy, Archana Kajita, Masahiro Wade, Paul A. TI The transcription factor snail mediates epithelial to mesenchymal transitions by repression of estrogen receptor-alpha SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER CELLS; E-CADHERIN EXPRESSION; GENE-EXPRESSION; TGF-BETA; TUMOR-CELLS; MECHANISMS; CARCINOMA; CHROMATIN; GROWTH; SUPERFAMILY AB The estrogen receptor (ER)-alpha (ESR1) is a key regulatory molecule in mammary epithelial cell development. Loss of ER-alpha in breast cancer is correlated with poor prognosis, increased recurrence after treatment, and an elevated incidence of metastasis. A proposed molecular pathway by which ER-alpha acts to constrain invasive growth in breast cancer cells involves direct, ER-alpha-dependent expression of metastasis-associated protein 3, a cell-type-specific component of the Mi-2/NuRD chromatin remodeling complex. MTA3 in turn represses expression of Snail, a transcription factor linked to epithelial to mesenchymal transition and cancer metastasis. To elucidate its role(s) in epithelial to mesenchymal transition (EMT), we expressed Snail in the noninvasive, ER-alpha-positive MCF-7 cell line. Snail expression led to decreased cell-cell adhesion and increased cell invasiveness. Furthermore, we observed loss of ER-alpha expression at both the RNA and protein level that was accompanied by direct interaction of Snail with regulatory DNA sequences at the ESR1 locus. A consequence of loss of ER-alpha function in this system was the increased abundance of key components of the TGF-beta signaling pathway. Thus, cross-talk among ER-alpha, Snail, and the TGF-beta pathway appears to control critical phenotypic properties of breast cancer cells. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Wade, PA (reprint author), NIEHS, Mol Carcinogenesis Lab, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM wadep2@niehs.nih.gov FU Intramural NIH HHS [Z01 ES101965-03] NR 68 TC 106 Z9 112 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2007 VL 21 IS 12 BP 2907 EP 2918 DI 10.1210/me.2007-0293 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 235OJ UT WOS:000251243900005 PM 17761946 ER PT J AU Cogliati, T Delgado-Romero, P Norwitz, ER Guduric-Fuchs, J Kaiser, UB Wray, S Kirsch, IR AF Cogliati, Tiziana Delgado-Romero, Petra Norwitz, Errol R. Guduric-Fuchs, Jasenka Kaiser, Ursula B. Wray, Susan Kirsch, Ilan R. TI Pubertal impairment in Nhlh2 null mice is associated with hypothalamic and pituitary deficiencies SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; DEVELOPING NERVOUS-SYSTEM; LOOP-HELIX GENES; GNRH NEURONS; NEUROPEPTIDE-Y; RECEPTOR GENE; LHRH NEURONS; DIFFERENTIAL REGULATION; ANTERIOR-PITUITARY; OLFACTORY AXONS AB Pubertal development is impaired in mice lacking the basic helix-loop-helix transcription factor Nhlh2. The mechanisms underlying changes in reproduction in Nhlh2-deficient mice (Nhlh2(-/-)) are unclear. Here we show that hypothalamic GnRH-1 content is reduced in adult Nhlh2(-/-) mice as is the number of GnRH-1 neurons localized to mid- and caudal hypothalamic regions. This reduction was detected postnatally after normal migration of GnRH-1 neurons within nasal regions had occurred. Phenotype rescue experiments showed that female Nhlh2(-/-) mice were responsive to estrogen treatment. In contrast, puberty could not be primed in female Nhlh2(-/-) mice with a GnRH-1 regimen. The adenohypophysis of Nhlh2(-/-) mice was hypoplastic although it contained a full complement of the five anterior pituitary cell types. GnRH-1 receptors (GnRHRs) were reduced in Nhlh2(-/-) pituitary gonadotropes as compared with wild type. In vitro assays indicated that Nhlh2 expression is regulated in parallel with GnRHR expression. However, direct transcriptional activity of Nhlh2 on the GnRHR promoter was not found. These results indicate that Nhlh2 plays a role in the development and functional maintenance of the hypothalamic-pituitary-gonadal axis at least at two levels: 1) in the hypothalamus by regulating the number and distribution of GnRH-1 neurons and, 2) in the developing and mature adenohypophysis. C1 Natl Inst Neurol Disorders, Cellular & Dev Neurobiol Sect, Bethesda, MD 20892 USA. Stroke Natl Inst Hlth, Bethesda, MD 20892 USA. Natl Canc Inst, Ctr Canc Res, Genet Branch, Bethesda, MD 20889 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Queens Univ Belfast, Sch Biomed Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North Ireland. RP Wray, S (reprint author), Natl Inst Neurol Disorders, Cellular & Dev Neurobiol Sect, Bldg 35,Room 3A-1012, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov; Ikirsch@amgen.com OI wray, susan/0000-0001-7670-3915 FU Intramural NIH HHS; NICHD NIH HHS [R01 HD19938] NR 61 TC 11 Z9 11 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2007 VL 21 IS 12 BP 3013 EP 3027 DI 10.1210/me.2005-0337 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 235OJ UT WOS:000251243900014 PM 17717072 ER PT J AU Quaynor, S Hu, L Leung, PK Feng, H Mores, N Krsmanovic, LZ Catt, KJ AF Quaynor, Samuel Hu, Lian Leung, Po Ki Feng, Hao Mores, Nadia Krsmanovic, Lazar Z. Catt, Kevin J. TI Expression of a functional G protein-coupled receptor 54-kisspeptin autoregulatory system in hypothalamic gonadotropin-releasing hormone neurons SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RESONANCE ENERGY-TRANSFER; KISSPEPTIN NEURONS; GNRH NEURONS; KISS-1; GPR54; SECRETION; PEPTIDE; AGONIST; PUBERTY; GENE AB The G protein-coupled receptor 54 (GPR54) and its endogenous ligand, kisspeptin, are essential for activation and regulation of the hypothalamic-pituitarygonadal axis. Analysis of RNA extracts from individually identified hypothalamic GnRH neurons with primers for GnRH, kisspeptin-1, and GPR54 revealed expression of all three gene products. Also, constitutive and GnRH agonist-induced bioluminescence resonance energy transfer between Renilla luciferase-tagged GnRH receptor and GPR54 tagged with green fluorescent protein, expressed in human embryonic kidney 293 cells, revealed heterooligomerization of the two receptors. Whole cell patch-clamp recordings from identified GnRH neurons showed initial depolarizing effects of kisspeptin on membrane potential, followed by increased action potential firing. In perifusion studies, treatment of GT1-7 neuronal cells with kisspeptin-10 increased GnRH peak amplitude and duration. The production and secretion of kisspeptin in cultured hypothalamic neurons and GT1-7 cells were detected by a specific RIA and was significantly reduced by treatment with GnRH. The expression of kisspeptin and GPR54 mRNAs in identified hypothalamic GnRH neurons, as well as kisspeptin secretion, indicate that kisspeptins may act as paracrine and/or autocrine regulators of the GnRH neuron. Stimulation of GnRH secretion by kisspeptin and the opposing effects of GnRH on kisspeptin secretion indicate that GnRH receptor/GnRH and GPR54/kisspeptin autoregulatory systems are integrated by negative feedback to regulate GnRH and kisspeptin secretion from GnRH neurons. C1 NICHHD, Endocrinol & Reprod Res Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Krsmanovic, LZ (reprint author), NICHHD, Endocrinol & Reprod Res Branch, Natl Inst Hlth, Bldg 49,Room 6A-36, Bethesda, MD 20892 USA. EM lazar@mail.nih.govA OI MORES, Nadia/0000-0002-4197-0914 FU Intramural NIH HHS NR 41 TC 41 Z9 44 U1 0 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2007 VL 21 IS 12 BP 3062 EP 3070 DI 10.1210/me.2007-0207 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 235OJ UT WOS:000251243900018 PM 17698953 ER PT J AU Brady, R AF Brady, Roscoe TI Current and future therapies for hereditary metabolic disorders SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 3rd Annual World Symposium on Lysosomal Disease Networks CY DEC 07-09, 2006 CL Orlando, FL C1 [Brady, Roscoe] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. NR 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2007 VL 92 IS 4 MA 17 BP S15 EP S15 DI 10.1016/j.ymgme.2007.08.022 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 247CF UT WOS:000252054000032 ER PT J AU Clarke, J West, M Bultas, J Askari, M Schiffmann, R AF Clarke, Joseph West, M. Bultas, J. Askari, M. Schiffmann, R. TI Alternative dosing regimens of agalsidase alfa (Replagal (R)) in Fabry disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 3rd Annual World Symposium on Lysosomal Disease Networks CY DEC 07-09, 2006 CL Orlando, FL C1 [Clarke, Joseph] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [West, M.] Queen Elizabeth II Hosp, Halifax, NS, Canada. [Bultas, J.] Charles Univ Hosp, Prague, Czech Republic. [Askari, M.; Schiffmann, R.] Natl Inst Hlth, Bethesda, MD USA. NR 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2007 VL 92 IS 4 MA 62 BP S25 EP S25 DI 10.1016/j.ymgme.2007.08.067 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 247CF UT WOS:000252054000069 ER PT J AU Schiffmann, R Chris, H Catherine, D Elin, DP Ed, F Roscoe, B Larry, A Pauline, C Ashok, V AF Schiffmann, Raphael Chris, Harris Catherine, DeVile Elin, Davis-Pope Ed, Fitzgibbon Roscoe, Brady Larry, Abel Pauline, Campbell Ashok, Vellodi TI Two-year oral miglustat in Gaucher disease type III SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 3rd Annual World Symposium on Lysosomal Disease Networks CY DEC 07-09, 2006 CL Orlando, FL C1 [Schiffmann, Raphael] NIH, NINDS, Bethesda, MD 20892 USA. [Ed, Fitzgibbon; Roscoe, Brady] NIH, Bethesda, MD 20892 USA. [Chris, Harris; Pauline, Campbell] Univ Plymouth, Plymouth PL4 8AA, Devon, England. [Catherine, DeVile; Ashok, Vellodi] UCL, Inst Child Hlth, London WC1E 6BT, England. [Elin, Davis-Pope] Great Ormond St Hosp Sick Children, Melbourne, Vic, Australia. [Larry, Abel] Univ Melbourne, Melbourne, Vic, Australia. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2007 VL 92 IS 4 MA 107 BP S33 EP S33 DI 10.1016/j.ymgme.2007.08.112 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 247CF UT WOS:000252054000100 ER PT J AU Schiffmann, R Krokhin, OV Wilkins, JA Gelderman, MP Goldin, E Moore, DF AF Schiffmann, Raphael Krokhin, Oleg V. Wilkins, John A. Gelderman, Monique P. Goldin, Ehud Moore, David F. TI Fabry disease - A patient and knock-out mouse study utilizing a systems biology approach SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 3rd Annual World Symposium on Lysosomal Disease Networks CY DEC 07-09, 2006 CL Orlando, FL C1 [Schiffmann, Raphael] NINDS, Natl Inst Hlth, Bethesda, MD 20892 USA. [Moore, David F.] Univ Manitoba, Sect Proteom & Syst Biol, Winnipeg, MB, Canada. [Krokhin, Oleg V.; Wilkins, John A.] Univ Manitoba, Manitoba Ctr Proteom & Syst Biol, Winnipeg, MB R3T 2N2, Canada. [Goldin, Ehud] NHGRI, Bethesda, MD 20892 USA. [Gelderman, Monique P.] NINDS, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. NR 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2007 VL 92 IS 4 MA 27 BP S17 EP S18 DI 10.1016/j.ymgme.2007.08.032 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 247CF UT WOS:000252054000042 ER PT J AU Sidransky, E Goker-Alpan, O Urban, D Cookson, M Giasson, B Stubblefield, BK AF Sidransky, Ellen Goker-Alpan, Ozlem Urban, Daniel Cookson, Mark Giasson, Benoit Stubblefield, Barbara K. TI Mutant glucocerebrosidase and the synucleinopathies SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 3rd Annual World Symposium on Lysosomal Disease Networks CY DEC 07-09, 2006 CL Orlando, FL C1 [Sidransky, Ellen; Goker-Alpan, Ozlem; Urban, Daniel; Cookson, Mark; Giasson, Benoit; Stubblefield, Barbara K.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2007 VL 92 IS 4 BP S33 EP S33 DI 10.1016/j.ymgme.2007.08.113 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 247CF UT WOS:000252054000101 ER PT J AU Sidransky, E AF Sidransky, Ellen TI Gaucher disease: Complexity in a "simple" disorder SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 3rd Annual World Symposium on Lysosomal Disease Networks CY DEC 07-09, 2006 CL Orlando, FL C1 [Sidransky, Ellen] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2007 VL 92 IS 4 MA 18 BP S15 EP S15 DI 10.1016/j.ymgme.2007.08.023 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 247CF UT WOS:000252054000033 ER PT J AU Tifft, C Adams, DR Morgan, CP AF Tifft, Cynthia Adams, D. R. Morgan, C. P. TI Miglustat improves function in patients with juvenile GM1 gangliosidosis SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 3rd Annual World Symposium on Lysosomal Disease Networks CY DEC 07-09, 2006 CL Orlando, FL C1 [Tifft, Cynthia] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Adams, D. R.; Morgan, C. P.] NHGRI, NIH, Bethesda, MD USA. [Adams, D. R.; Morgan, C. P.] Childrens Natl Med Ctr, Div Genet & Metab, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2007 VL 92 IS 4 MA 55 BP S24 EP S24 DI 10.1016/j.ymgme.2007.08.060 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 247CF UT WOS:000252054000065 ER PT J AU Urban, D Zheng, W Goker-Alpan, O Goldin, E Padia, J Inglese, J Goswami, A Austin, C Sidransk, E AF Urban, Daniel Zheng, Wei Goker-Alpan, Ozlem Goldin, Ehud Padia, Janak Inglese, Jim Goswami, Aashish Austin, Chris Sidransk, Ellen TI The identification and characterization of glueocerebrosidase activators and inhibitors as potential therapeutic agents for Gaucher disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 3rd Annual World Symposium on Lysosomal Disease Networks CY DEC 07-09, 2006 CL Orlando, FL C1 [Urban, Daniel; Zheng, Wei; Goker-Alpan, Ozlem; Goldin, Ehud; Padia, Janak; Inglese, Jim; Goswami, Aashish; Austin, Chris] NHGRI, Natl Inst Hlth, Med Genet Branch, Bethesda, MD USA. [Urban, Daniel; Zheng, Wei; Goker-Alpan, Ozlem; Goldin, Ehud; Padia, Janak; Inglese, Jim; Goswami, Aashish; Austin, Chris; Sidransk, Ellen] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD USA. NR 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2007 VL 92 IS 4 MA 47 BP S22 EP S22 DI 10.1016/j.ymgme.2007.08.052 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 247CF UT WOS:000252054000057 ER PT J AU Tsai-Morris, CH Koh, E Sheng, Y Maeda, Y Gutti, R Namiki, M Dufau, ML AF Tsai-Morris, Chon-Hwa Koh, Eitetsu Sheng, Yi Maeda, Yuji Gutti, Ravi Namiki, Mikio Dufau, Maria L. TI Polymorphism of the GRTH/DDX25 gene in normal and infertile Japanese men: a missense mutation associated with loss of GRTH phosphorylation SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE GRTH/DDX25 mutation; missense mutation; single nucleotide polymorphism; azoospermia; infertility ID TESTICULAR RNA HELICASE; DEAD-BOX PROTEINS; Y-CHROMOSOME; HUMAN SPERMATOGENESIS; FAMILY; VASA; MICRODELETIONS; TRANSLATION; AZOOSPERMIA; DELETIONS AB The gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is present in Leydig and germ cells of rodents, and is essential for fertility in mice. This study evaluated the incidence of GRTH/DDX25 gene mutations in a group of infertile patients with non-obstructive azoospermia (NOA), 85% with a preponderance of Sertoli cells in the seminiferous tubule and 15% with spermatogenic arrest, and compared them to a group of fertile subjects. Exonic sequences in the GRTH gene were screened using denaturing high-performance liquid chromatography of the genomic DNA from 143 NOA and 100 fertile Japanese men. A unique heterozygous missense mutation Arg(242)His in exon 8 was identified in 5.8% of Sertoli cell-only patients and in 1% of normal subjects. Although the mutant protein was efficiently expressed in COS-1 cells, only the 56 kDa nuclear/cytoplasmic non-phosphorylated species was present, whereas the 61 kDa cytosolic phosporylated species was absent. In addition, a silent mutation was identified in exon 11 in NOA subjects. The Arg(242)His missense mutation of the GRTH/DDX25 gene associated with expression of a protein with reduced basicity, and the absence of the phospho-GRTH species, could be of relevance to some of the functional aspects of the protein that impact on germ cell development and/or function. C1 [Tsai-Morris, Chon-Hwa; Sheng, Yi; Maeda, Yuji; Gutti, Ravi; Dufau, Maria L.] NICHHD, Natl Inst Hlth, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), Bldg 49,6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM dufaum@mail.nih.gov OI Gutti, Ravi/0000-0002-0912-5796 FU Intramural NIH HHS NR 31 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD DEC PY 2007 VL 13 IS 12 BP 887 EP 892 DI 10.1093/molehr/gam065 PG 6 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 245AU UT WOS:000251907500007 PM 17848414 ER PT J AU Blumberg, PM AF Blumberg, Peter M. TI Lighting a backfire to quench the blaze: A combined drug approach targeting the vanilloid receptor TRPV1 SO MOLECULAR INTERVENTIONS LA English DT Editorial Material ID CAPSAICIN RECEPTOR; PAIN PATHWAY; RESINIFERATOXIN; CHANNELS; SELECTIVITY; ANTAGONISTS; ACTIVATION; MECHANISMS; NEURONS; BINDING C1 Natl Canc Inst, Ctr Canc Res, Tumor Promot Sect, Lab Can Biol & Genet, Bethesda, MD 20892 USA. RP Blumberg, PM (reprint author), Natl Canc Inst, Ctr Canc Res, Tumor Promot Sect, Lab Can Biol & Genet, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih NR 30 TC 2 Z9 3 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD DEC 1 PY 2007 VL 7 IS 6 BP 310 EP 312 DI 10.1124/mi.7.6.5 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 267HA UT WOS:000253498900003 PM 18199852 ER PT J AU Kinders, R Parchment, RE Ji, J Kummar, S Murgo, AJ Gutierrez, M Collins, J Rubinstein, L Pickeral, O Steinberg, SM Yang, S Hollingshead, M Chen, A Helman, L Wiltrout, R Simpson, M Tomaszewski, JE Doroshow, JH AF Kinders, Robert Parchment, Ralph E. Ji, Jay Kummar, Shivaani Murgo, Anthony J. Gutierrez, Martin Collins, Jerry Rubinstein, Larry Pickeral, Oxana Steinberg, Seth M. Yang, Sherry Hollingshead, Melinda Chen, Alice Helman, Lee Wiltrout, Robert Simpson, Mel Tomaszewski, Joseph E. Doroshow, James H. TI Phase 0 clinical trials in cancer drug development: From FDA guidance to clinical practice SO MOLECULAR INTERVENTIONS LA English DT Review ID MODELS; BIOMARKERS; HERCEPTIN AB The Food and Drug Administration (FDA) recently introduced the Exploratory Investigational New Drug Guidance to expedite the clinical evaluation of new therapeutic and imaging agents. Early clinical studies performed under the auspices of this guidance, so-called "Phase 0" trials, have been initiated at the National Cancer Institute to integrate qualified pharmacodynamic biomarker assays into first-in-human cancer clinical trials of molecularly targeted agents. The goal of this integration is to perform molecular proof-of-concept investigations at the earliest stage of cancer drug development. Phase 0 trials do not offer any possibility of patient benefit; instead, intensive, real-time pharmacodynamic and pharmacokinetic analyses of patient tumor samples and/or surrogate tissues are performed to inform subsequent trials. Phase 0 studies do not replace formal Phase I drug safety testing and require a substantial investment of resources in assay development early on; however, they offer the promise of more rational selection of agents for further, large-scale development as well as the molecular identification of potential therapeutic failures early in the development process. C1 [Kummar, Shivaani; Gutierrez, Martin; Steinberg, Seth M.; Helman, Lee; Wiltrout, Robert; Doroshow, James H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Murgo, Anthony J.; Collins, Jerry; Rubinstein, Larry; Pickeral, Oxana; Yang, Sherry; Hollingshead, Melinda; Chen, Alice; Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Natl Clin Target Validat Lab, Dev Therapeut Program,Biol Testing Branch, Bethesda, MD 20892 USA. [Kinders, Robert; Parchment, Ralph E.; Ji, Jay; Simpson, Mel] NCI, SAIC Frederick Inc, Appl Dev Res Support Directorate, Lab Human Toxicol & Pharmacol, Frederick, MD 21702 USA. [Parchment, Ralph E.] Hipple Canc Res Ctr, Pharmacol & Toxicol Lab, Dayton, OH USA. [Parchment, Ralph E.] Wayne State Univ, Detroit, MI 48202 USA. [Parchment, Ralph E.] Karmanos Canc Inst, Pharmacol Core, Detroit, MI USA. RP Kinders, R (reprint author), Kansas Ctr Basic Canc Res, Advisory Council, Manhattan, KS USA. FU NCI NIH HHS [N01-CO12400] NR 21 TC 48 Z9 52 U1 0 U2 8 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD DEC 1 PY 2007 VL 7 IS 6 BP 325 EP 334 DI 10.1124/mi.7.6.9 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 267HA UT WOS:000253498900005 PM 18199854 ER PT J AU Li, M Cha, DJ Lai, YP Villaruz, AE Sturdevant, DE Otto, M AF Li, Min Cha, David J. Lai, Yuping Villaruz, Amer E. Sturdevant, Daniel E. Otto, Michael TI The antimicrobial peptide-sensing system aps of Staphylococcus aureus SO MOLECULAR MICROBIOLOGY LA English DT Article ID RESISTANCE; VIRULENCE; DEFENSES; MRSA; REPLACEMENT; INFECTIONS; EXPRESSION; CARNOSUS; GENES AB Staphylococcus aureus is a leading cause of hospital-associated and, more recently, community-associated infections caused by highly virulent methicillin-resistant strains (CA-MRSA). S. aureus survival in the human host is largely defined by the ability to evade attacks by antimicrobial peptides (AMPs) and other mechanisms of innate host defence. Here we show that AMPs induce resistance mechanisms in CA-MRSA via the aps AMP sensor/regulator system, including (i) the D-alanylation of teichoic acids, (ii) the incorporation of lysylphosphatidylglycerol in the bacterial membrane and a concomitant increase in lysine biosynthesis, and (iii) putative AMP transport systems such as the vraFG transporter, for which we demonstrate a function in AMP resistance. In contrast to the aps system of S. epidermidis, induction of the aps response in S. aureus was AMP-selective due to structural differences in the AMP binding loop of the ApsS sensor protein. Finally, using a murine infection model, we demonstrate the importance of the aps regulatory system in S. aureus infection. This study shows that while significant interspecies differences exist in the AMP-aps interaction, the AMP sensor system aps is functional and efficient in promoting resistance to a variety of AMPs in a clinically relevant strain of the important human pathogen S. aureus. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Res Technol Sect, Genom Unit, Rocky Mt Labs,NIH, Hamilton, MT USA. E China Normal Univ, Sch Life Sci, Shanghai 200062, Peoples R China. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS NR 33 TC 140 Z9 143 U1 8 U2 26 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 2007 VL 66 IS 5 BP 1136 EP 1147 DI 10.1111/j.1365-2958.2007.05986.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 231AD UT WOS:000250917200008 PM 17961141 ER PT J AU Chandran, J Ding, JH Cai, H AF Chandran, Jayanth Ding, Jinhui Cai, Huaibin TI Alsin and the molecular pathways of amyotrophic lateral sclerosis SO MOLECULAR NEUROBIOLOGY LA English DT Article DE amyotrophic lateral sclerosis (ALS); ALS2; Alsin; Rab5; mouse model; guanine-nucleotide-exchange factor; primary lateral sclerosis; hereditary spastic paraplegia ID NUCLEOTIDE EXCHANGE FACTOR; MOTOR-NEURON DISEASE; HEREDITARY SPASTIC PARAPLEGIA; SMALL GTPASE RAB5; ENDOSOME TRAFFICKING; ALS2-DEFICIENT MICE; MISSENSE MUTATION; MUSCULAR-ATROPHY; GENE; DEGENERATION AB Autosomal recessive mutations in the ALS2 gene lead to a clinical spectrum of motor dysfunction including juvenile onset amyotrophic lateral sclerosis (ALS2), primary lateral sclerosis, and hereditary spastic paraplegia. The 184-kDa alsin protein, encoded by the full-length ALS2 gene, contains three different guanine-nucleotide-exchange factor-like domains, which may play a role in the etiology of the disease. Multiple in vitro biochemical and cell biology assays suggest that alsin dysfunction affects endosome trafficking through a Rab5 small GTPase family-mediated mechanism. Four ALS2-deficient mouse models have been generated by different groups and used to study the behavioral and pathological impact of alsin deficiency. These mouse models largely fail to recapitulate hallmarks of motor neuron disease, but the subtle deficits that are observed in behavior and pathology have aided in our understanding of the relationship between alsin and motor dysfunction. In this review, we summarize recent clinical and molecular reports regarding alsin and attempt to place these results within the larger context of motor neuron disease. C1 NIH, NIA, Neurogenet Lab, Unit Transgenesis, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Cai, H (reprint author), NIH, NIA, Neurogenet Lab, Unit Transgenesis, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA. EM caih@mail.nih.gov RI Cai, Huaibin/H-3359-2013 OI Cai, Huaibin/0000-0002-8596-6108 FU Intramural NIH HHS [Z99 AG999999, Z01 AG000959-04] NR 52 TC 22 Z9 22 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD DEC PY 2007 VL 36 IS 3 BP 224 EP 231 DI 10.1007/s12035-007-0034-x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 223OM UT WOS:000250380600002 PM 17955197 ER PT J AU Kikuchi, R Kusuhara, H Hattori, N Kim, I Shiota, K Gonzalez, FJ Sugiyama, Y AF Kikuchi, Ryota Kusuhara, Hiroyuki Hattori, Naka Kim, Insook Shiota, Kunio Gonzalez, Frank J. Sugiyama, Yuichi TI Regulation of tissue-specific expression of the human and mouse urate transporter 1 gene by hepatocyte nuclear factor 1 alpha/beta and DNA methylation SO MOLECULAR PHARMACOLOGY LA English DT Article ID RENAL HYPOURICEMIA; TRANSCRIPTION; HOMEOPROTEIN; TRANSPORT; KIDNEY; YOUNG; ACID; HNF1; MUTATIONS; NETWORK AB Expression of Urate transporter 1 (URAT1/SLC22A12) is restricted to the proximal tubules in the kidney, where it is responsible for the tubular reabsorption of urate. To elucidate the mechanism underlying its tissue-specific expression, the transcriptional regulation of the hURAT1 and mUrat1 genes was investigated. Hepatocyte nuclear factor 1 alpha (HNF1 alpha) and HNF1 beta positively regulate minimal promoter activity of the URAT1 gene as shown by reporter gene assays. Electrophoretic mobility shift assays revealed binding of HNF1 alpha and/or HNF1 beta to the HNF1 motif in the hURAT1 promoter. Furthermore, the mRNA expression of Urat1 is reduced in the kidneys of Hnf1 alpha-null mice compared with wild-type mice, confirming the indispensable role of HNF1 alpha in the constitutive expression of URAT1 genes. It was also shown that the proximal promoter region of mUrat1 was hypermethylated in the liver and kidney medulla, whereas this region was relatively hypomethylated in the kidney cortex. These methylation profiles are in a good agreement with the proximal tubule-restricted expression of mUrat1 in the kidney cortex. Taken together, these results strongly suggest that tissue-specific expression of the URAT1 genes is coordinately regulated by the transcriptional activation by HNF1 alpha/HNF1 beta heterodimer and repression by DNA methylation. C1 Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Mol Pharmacokinet, Tokyo, Japan. Univ Tokyo, Dept Anim Res Sci Vet Med Sci, Tokyo, Japan. NIH, Natl Canc Inst, Lab Metab, Bethesda, MD 20892 USA. RP Kikuchi, R (reprint author), Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Mol Pharmacokinet, Tokyo, Japan. NR 35 TC 40 Z9 42 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2007 VL 72 IS 6 BP 1619 EP 1625 DI 10.1124/mol.107.039701 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 232OT UT WOS:000251029700025 PM 17855651 ER PT J AU Werner, S Sugui, JA Steinberg, G Deising, HB AF Werner, Stefan Sugui, Janyce A. Steinberg, Gero Deising, Holger B. TI A chitin synthase with a myosin-like motor domain is essential for hyphal growth, appressorium differentiation, and pathogenicity of the maize anthracnose fungus Colletotrichum graminicola SO MOLECULAR PLANT-MICROBE INTERACTIONS LA English DT Article DE force measurement; fungal cell wall ID YEAST-CELL WALL; ASPERGILLUS-NIDULANS; CLASS-V; USTILAGO-MAYDIS; COCHLIOBOLUS-HETEROSTROPHUS; SACCHAROMYCES-CEREVISIAE; CONIDIOPHORE DEVELOPMENT; MORPHOGENETIC PROCESSES; GLOMERELLA-GRAMINICOLA; FUSARIUM-OXYSPORUM AB Chitin synthesis contributes to cell wall biogenesis and is essential for invasion of solid substrata and Pathogenicity of filamentous fungi. In contrast to yeasts, filamentous fungi contain up to 10 chitin synthases (CHS), which might reflect overlapping functions and indicate their complex lifestyle. Previous studies have shown that a class VI CHS of the maize anthracuose fungus Colletotrichum graminicola is essential for cell wall synthesis of conidia and vegetative hyphae. Here, we report on cloning and characterization of three additional CHS genes, CgChsI, CgChsIII, and CgChsV, encoding class 1, 111, and V CHS, respectively. All CHS genes are expressed during vegetative and pathogenic development. Delta CgChsI and Delta CgChsIII mutants did not differ significantly from the wild-type isolate with respect to hyphal growth and pathogenicity. In contrast, null mutants in the CgChsV gene, which encodes a CHS with an N-terminal myosin-like motor domain, are strongly impaired in vegetative growth and pathogenicity. Even in osmotically stabilized media, vegetative hyphae of Delta CgChsV mutants exhibited large balloon-like swellings, appressorial walls appeared to disintegrate during maturation, and infection cells were nonfunctional. Surprisingly, Delta CgChsV mutants were able to form dome-shaped hyphopodia that exerted force and showed host cell wall penetration rates comparable with the wild type. However, infection hyphae that formed within the plant cells exhibited severe swellings and were not able to proceed with plant colonization efficiently. Consequently, Delta CgChsV mutants did not develop macroscopically visible anthracnose disease symptoms and, thus, were nonpathogenic. C1 Natl Inst Hlth, NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. Univ Halle Wittenberg, Inst Agr & Nutr Sci, Phytopathol & Plant Protect, D-06099 Halle, Germany. Max Planck Inst Terr Microbiol, D-35043 Marburg, Germany. RP Deising, HB (reprint author), Natl Inst Hlth, NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. EM holger.deising@landw.uni-halle.de NR 62 TC 57 Z9 60 U1 5 U2 13 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0894-0282 J9 MOL PLANT MICROBE IN JI Mol. Plant-Microbe Interact. PD DEC PY 2007 VL 20 IS 12 BP 1555 EP 1567 DI 10.1094/MPMI-20-12-1555 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Plant Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Plant Sciences GA 232EQ UT WOS:000251001500010 PM 17990963 ER PT J AU Cotrim, AP Sowers, A Mitchell, JB Baum, BJ AF Cotrim, Ana P. Sowers, Anastasia Mitchell, James B. Baum, Bruce J. TI Prevention of irradiation-induced salivary hypofunction by microvessel protection in mouse salivary glands SO MOLECULAR THERAPY LA English DT Article ID RADIATION-INDUCED APOPTOSIS; RAT SUBMANDIBULAR-GLANDS; FIBROBLAST-GROWTH-FACTOR; MEDIATED GENE-TRANSFER; NECK RADIOTHERAPY; CELL-LINE; EXPRESSION; CERAMIDE; DAMAGE; HEAD AB Treatment of most head and neck cancers includes radiotherapy. Salivary glands (SGs) in the irradiation (IR) field are irreversibly damaged resulting in severe hyposalivation. We evaluated the importance of SG endothelial cells to this IR-induced injury, and whether serotype 5 adenoviral (Ad5) vector-mediated transfer of basic fibroblast growth factor (AdbFGF) or vascular endothelial growth factor (AdVEGF) complementary DNAs would afford radioprotection. Four hours after IR, microvessel density (MVD) in SGs decreased by similar to 45%. However, if mice were pretreated with either AdVEGF or AdbFGF 48 hours before IR the loss in MVD was significantly reduced. An irrelevant vector, AdLacZ, encoding Escherichia coli beta-galactosidase, was without effect. After 8 weeks, IR reduced salivary flow by similar to 65% in untreated mice. Mice pre-treated (using 5 x 109 particles/gland 48 hours prior to IR) with AdLacZ exhibited a reduction in salivary flow similar to untreated mice receiving IR. However, irradiated mice pre-treated with AdbFGF or AdVEGF showed a significant improvement in their salivary flow, to similar to 70% (P < 0.01) and 80% (P < 0.01), respectively, compared to non-irradiated control mice. These results are consistent with the notion that injury to the adjacent microvasculature may play an important role in SG radiation damage. Furthermore, our results suggest that a local transient treatment directed at protecting SG endothelial cells may be beneficial for patients undergoing IR for head and neck cancer. C1 NIH, Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NIH, Natl Canc Inst, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Cotrim, AP (reprint author), NIH, Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, Bldg 10, Bethesda, MD 20892 USA. EM acotrim@nidcr.nih.gov FU Intramural NIH HHS NR 37 TC 44 Z9 49 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD DEC PY 2007 VL 15 IS 12 BP 2101 EP 2106 DI 10.1038/sj.mt.6300296 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 235XE UT WOS:000251266800009 PM 17726456 ER PT J AU Kissling, GE Dertinger, SD Hayashi, M MacGregord, JT AF Kissling, Grace E. Dertinger, Stephen D. Hayashi, Makoto MacGregord, James T. TI Sensitivity of the erythrocyte micronucleus assay: Dependence on number of cells scored and inter-animal variability SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE erythrocyte micronucleus assay; flow cytometry; binomial counting error; inter-animal variability; power calculation ID PERIPHERAL-BLOOD RETICULOCYTES; FLOW-CYTOMETRIC ANALYSIS; VALIDATION; INDUCTION; RODENT; DAMAGE; RAT AB Until recently, the in vivo erythrocyte micronucleus assay has been scored using microscopy. Because the frequency of micronucleated cells is typically low, cell counts are subject to substantial binomial counting error. Counting error, along with inter-animal variability, limit the sensitivity of this assay. Recently, flow cytometric methods have been developed for scoring micronucleated erythrocytes and these methods enable many more cells to be evaluated than is possible with microscopic scoring. Using typical spontaneous micronucleus frequencies reported in mice, rats, and dogs we calculate the counting error associated with the frequency of micronucleated reticulocytes as a function of the number of reticulocytes scored. We compare this counting error with the interanimal variability determined by flow cytometric scoring of sufficient numbers of cells to assure that the counting error is less than the inter-animal variability, and calculate the minimum increases in micronucleus frequency that can be detected as a function of the number of cells scored. The data show that current regulatory guidelines allow low power of the test when spontaneous frequencies are low (e.g., <= 0.1%). Tables and formulas are presented that provide the necessary numbers of cells that must be scored to meet the recommendation of the International Working Group on Genotoxicity Testing that sufficient cells be scored to reduce counting error to less than the inter-animal variability, thereby maintaining a more uniform power of detection of increased micronucleus frequencies across laboratories and species. (c) 2007 Elsevier B.V. All rights reserved. C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. Litron Labs, Rochester, NY 14623 USA. Natl Inst Hlth Sci, Tokyo 1588501, Japan. Toxicol Consulting Serv, Arnold, MD 21012 USA. RP Kissling, GE (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. EM kissling@niehs.nih.gov FU Intramural NIH HHS [Z01 ES045003-11] NR 22 TC 25 Z9 29 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD DEC 1 PY 2007 VL 634 IS 1-2 BP 235 EP 240 DI 10.1016/j.mrgentox.2007.07.010 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 238VW UT WOS:000251477200026 PM 17851117 ER PT J AU Hall, JB Dobrovolskaia, MA Patri, AK McNeil, SE AF Hall, Jennifer B. Dobrovolskaia, Marina A. Patri, Anil K. McNeil, Scott E. TI Characterization of nanoparticles for therapeutics SO NANOMEDICINE LA English DT Review DE biodistribution; diagnostics; dynamic light scattering; electron microscopy; hemolysis; nanoparticle; nanotechnology; phagocytosis; safety evaluation; toxicity ID DRUG-DELIVERY SYSTEMS; IN-VITRO; COMPLEMENT ACTIVATION; GENE DELIVERY; POLYSTYRENE MICROSPHERES; POLYMERIC NANOPARTICLES; BLOOD COMPATIBILITY; ACID) NANOPARTICLES; PROTEIN ADSORPTION; CARBON NANOTUBES AB Nanotechnology offers many advantages to traditional drug design, delivery and medical diagnostics; however, nanomedicines present considerable challenges for preclinical development. Nanoparticle constructs intended for medical applications consist of a wide variety of materials, and their small size, unique physicochemical properties and biological activity often require modification of standard characterization techniques. A rational characterization strategy for nanomedicines includes physicochemical characterization, sterility and pyrogenicity assessment, biodistribution (absorption, distribution, metabolism and excretion [ADME]) and toxicity characterization, which includes both in vitro tests and in vivo animal studies. Here, we highlight progress for a few methods that are uniquely useful for nanoparticles or are indicative of their toxicity or efficacy. C1 [Hall, Jennifer B.; Dobrovolskaia, Marina A.; Patri, Anil K.; McNeil, Scott E.] SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Program, NCI Frederick, Frederick, MD 21702 USA. RP McNeil, SE (reprint author), SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Program, NCI Frederick, 1050 Boyles St Bldg 469, Frederick, MD 21702 USA. EM ncl@ncifcrf.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 76 TC 144 Z9 145 U1 8 U2 61 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD DEC PY 2007 VL 2 IS 6 BP 789 EP 803 DI 10.2217/17435889.2.6.789 PG 15 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 250YG UT WOS:000252336600007 PM 18095846 ER PT J AU Wei, CM Liu, NH Xu, PY Heller, M Tomalia, DA Haynie, DI Chang, EH Wang, K Lee, YS Lyubchenko, YL Bawa, R Tian, R Hanes, J Pun, S Meiners, JC Guo, PX AF Wei, Chiming Liu, Nanhai Xu, Pingyi Heller, Mike Tomalia, Donald A. Haynie, Donald I. Chang, Esther H. Wang, Kuan Lee, Yoon-Sik Lyubchenko, Yuri L. Bawa, Raj Tian, Ryan Hanes, Justin Pun, Suzie Meiners, Jens-Christian Guo, Peixuan TI From bench to bedside: successful translational nanomedicine Highlights of the Third Annual Meeting of the American Academy of Nanomedicine SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Editorial Material AB The Third Annual Meeting of the American Academy of Nanomedicine (AANM) was held at the University of California San Diego, in San Diego, California during September 7-8, 2007. The meeting was focused on successfid translational nanomedicine: from bench to bedside. There were four keynote lectures and eight scientific symposiums in this meeting. The researchers and investigators reported the results and process of current nanomedicine research and approaches to clinical applications. The meeting provided exciting information for nanomedicine clinical-related researches and strategy for further development of nanomedicine research which will be benefits to clinical practice. C1 [Wei, Chiming] Johns Hopkins Univ, Sch Med, Mol Nanomed Program, Baltimore, MD 21205 USA. [Wei, Chiming; Liu, Nanhai; Xu, Pingyi; Hanes, Justin] Johns Hopkins Univ, Baltimore, MD USA. [Liu, Nanhai] GanNan Med Coll, Ganzhou, Peoples R China. [Xu, Pingyi] Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou, Peoples R China. [Heller, Mike] Univ Calif San Diego, San Diego, CA USA. [Tomalia, Donald A.] Cent Michigan Univ, Dendrit Nanotechnol Inc, Mt Pleasant, MI USA. [Haynie, Donald I.] Artif Cell Technol Inc, New Haven, CT USA. [Chang, Esther H.] Georgetown Univ, Washington, DC USA. [Wang, Kuan] NIH, Washington, DC USA. [Lee, Yoon-Sik] Seoul Natl Univ, Seoul, South Korea. [Lyubchenko, Yuri L.] Univ Nebraska Med Ctr, Omaha, NE USA. [Bawa, Raj] LLC, Bawa Biotechnol Consult, Ashburn, VA USA. [Bawa, Raj] Rensselaer Polytech Inst, Troy, NY USA. [Tian, Ryan] Univ Arkansas, Fayetteville, AR 72701 USA. [Pun, Suzie] Univ Washington, Seattle, WA 98195 USA. [Meiners, Jens-Christian] Univ Michigan, Ann Arbor, MI 48109 USA. [Guo, Peixuan] Univ Cincinnati, Cincinnati, OH USA. RP Wei, CM (reprint author), Johns Hopkins Univ, Sch Med, Mol Nanomed Program, 600 N Wolfe St,Harvey 606, Baltimore, MD 21205 USA. EM chimingwei@gmail.com RI Guo, Peixuan/I-7184-2015; Tian, Z. Ryan /R-6671-2016 OI Tian, Z. Ryan /0000-0002-5644-8483 NR 0 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD DEC PY 2007 VL 3 IS 4 BP 322 EP 331 DI 10.1016/j.nano.2007.10.005 PG 10 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 242OU UT WOS:000251735900010 PM 18068093 ER PT J AU Wang, K AF Wang, K. TI Nanomechanics: force and signaling pathways SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 [Wang, K.] NIH, NIAMSD, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD DEC PY 2007 VL 3 IS 4 BP 340 EP 340 DI 10.1016/j.nano.2007.10.025 PG 1 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 242OU UT WOS:000251735900030 ER PT J AU Basu, S Grubina, R Huang, J Conradie, J Huang, Z Jeffers, A Jiang, A He, X Azarov, I Seibert, R Mehta, A Patel, R King, SB Hogg, N Ghosh, A Gladwin, MT Kim-Shapiro, DB AF Basu, Swati Grubina, Rozalina Huang, Jinming Conradie, Jeanet Huang, Zhi Jeffers, Anne Jiang, Alice He, Xiaojun Azarov, Ivan Seibert, Ryan Mehta, Atul Patel, Rakesh King, Stephen Bruce Hogg, Neil Ghosh, Abhik Gladwin, Mark T. Kim-Shapiro, Daniel B. TI Catalytic generation of N2O3 by the concerted nitrite reductase and anhydrase activity of hemoglobin SO NATURE CHEMICAL BIOLOGY LA English DT Article ID RED-BLOOD-CELLS; S-NITROSOHEMOGLOBIN; CORRELATION-ENERGY; NITROGEN-OXIDES; FLOW REGULATION; NO; OXIDATION; DEOXYHEMOGLOBIN; MECHANISM; HEME AB Nitrite reacts with deoxyhemoglobin to form nitric oxide (NO) and methemoglobin. Though this reaction is experimentally associated with NO generation and vasodilation, kinetic analysis suggests that NO should not be able to escape inactivation in the erythrocyte. We have discovered that products of the nitrite-hemoglobin reaction generate dinitrogen trioxide (N2O3) via a novel reaction of NO and nitrite-bound methemoglobin. The oxygen-bound form of nitrite-methemoglobin shows a degree of ferrous nitrogen dioxide (Fe(II)-NO2) character, so it may rapidly react with NO to form N2O3. N2O3 partitions in lipid, homolyzes to NO and readily nitrosates thiols, all of which are common pathways for NO escape from the erythrocyte. These results reveal a fundamental heme globin- and nitrite-catalyzed chemical reaction pathway to N2O3, NO and S-nitrosothiol that could form the basis of in vivo nitrite-dependent signaling. Because the reaction redox-cycles ( that is, regenerates ferrous heme) and the nitrite-methemoglobin intermediate is not observable by electron paramagnetic resonance spectroscopy, this reaction has been 'invisible' to experimentalists over the last 100 years. C1 Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Hlth Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD 20814 USA. Wake Forest Univ, Dept Chem, Winston Salem, NC 27109 USA. Univ Tromso, Dept Chem, N-9037 Tromso, Norway. Univ Tromso, Ctr Theoret & Computat Chem, N-9037 Tromso, Norway. Univ Orange Free State, Dept Chem, ZA-9301 Bloemfontein, South Africa. Wake Forest Univ, Sch Med, Wake Forest Univ Sch Biomed Engn & Sci, Virginia Tech, Winston Salem, NC 27157 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kim-Shapiro, DB (reprint author), Wake Forest Univ, Dept Phys, 1834 Wake Forest Rd, Winston Salem, NC 27109 USA. EM mgladwin@nih.gov; shapiro@wfu.edu RI Ghosh, Abhik/G-8164-2016; OI Ghosh, Abhik/0000-0003-1161-6364; Patel, Rakesh/0000-0002-1526-4303; Seibert, Ryan/0000-0002-9704-5330; Azarov, Ivan/0000-0002-9886-3298 FU Intramural NIH HHS; NHLBI NIH HHS [HL62198, HL58091, K02 HL078706, R37 HL058091]; NIGMS NIH HHS [GM55792] NR 51 TC 154 Z9 159 U1 2 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD DEC PY 2007 VL 3 IS 12 BP 785 EP 794 DI 10.1038/nchembio.2007.46 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 232OI UT WOS:000251028600013 PM 17982448 ER PT J AU Vecchio, G Robbins, J AF Vecchio, Giancarlo Robbins, Jacob TI Nino Salvatore's contribution to scientific collaboration between Europe and the US in endocrinology SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material C1 Univ Naples Federico 2, Naples, Italy. NIH, NIDDK, Clin Endocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD DEC PY 2007 VL 3 IS 12 BP 785 EP 785 DI 10.1038/ncpendmet0680 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 230HT UT WOS:000250868300001 PM 18026158 ER PT J AU Mannes, AJ Iadarola, MJ AF Mannes, Andrew J. Iadarola, Michael J. TI Complete pain relief: potential problems and diagnostic solutions SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Editorial Material ID LOW-BACK-PAIN; PERSISTENT PAIN; NEURONS C1 NIH, Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Bethesda, MD 20892 USA. NIH, Natl Inst Dent & Craniofacial Res, Dept Anesthesia & Surg Serv, Bethesda, MD 20892 USA. RP Iadarola, MJ (reprint author), NIH, Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, 49 Convent Dr,MSC 4410, Bethesda, MD 20892 USA. EM miadarola@dir.nidcr.nih.gov OI Mannes, Andrew/0000-0001-5834-5667 NR 10 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD DEC PY 2007 VL 3 IS 12 BP 648 EP 649 DI 10.1038/ncpneuro0660 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 236DF UT WOS:000251282500002 PM 17984990 ER PT J AU Houlden, H Johnson, J Gardner-Thorpe, C Lashley, T Hernandez, D Worth, P Singleton, AB Hilton, DA Holton, J Revesz, T Davis, MB Giunti, P Wood, NW AF Houlden, Henry Johnson, Janel Gardner-Thorpe, Christopher Lashley, Tammaryn Hernandez, Dena Worth, Paul Singleton, Andrew B. Hilton, David A. Holton, Janice Revesz, Tamas Davis, Mary B. Giunti, Paolo Wood, Nicholas W. TI Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11 SO NATURE GENETICS LA English DT Article ID DOMINANT CEREBELLAR ATAXIAS; ALZHEIMERS-DISEASE; CLINICAL-FEATURES; DISORDERS; PROTEIN; FAMILY AB The microtubule-associated protein tau ( encoded by MAPT) and several tau kinases have been implicated in neurodegeneration, but only MAPT has a proven role in disease. We identified mutations in the gene encoding tau tubulin kinase 2 ( TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue showed substantial cerebellar degeneration and tau deposition. These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration. C1 UCL Natl Hosp Neurol & Neurosurg, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. NIA, NIH, Neurogenet Lab, Mol Genet Unit, Bethesda, MD 20892 USA. Royal Devon & Exeter Hosp, Exeter EX2 5DW, Devon, England. Norwich Univ Hosp, Dept Neurol, Natl Hlth Serv, Norwich NR4 7UY, Norfolk, England. Derriford Hosp, Dept Histopathol, Plymouth PL6 8DH, Devon, England. RP Houlden, H (reprint author), UCL Natl Hosp Neurol & Neurosurg, Inst Neurol, Dept Mol Neurosci, Queen Square, London WC1N 3BG, England. EM h.houlden@ion.ucl.ac.uk; n.wood@ion.ucl.ac.uk RI Houlden, Henry/C-1532-2008; Lashley, Tammaryn/D-2583-2009; Johnson, Janel/A-7136-2010; Singleton, Andrew/C-3010-2009; Giunti, Paola /E-5526-2012; Wood, Nicholas/C-2505-2009; Holton, Janice/F-6831-2011; Revesz, Tamas/A-8732-2010 OI Houlden, Henry/0000-0002-2866-7777; Giunti, Paola /0000-0003-3508-4788; Wood, Nicholas/0000-0002-9500-3348; Holton, Janice/0000-0002-3882-5249; Revesz, Tamas/0000-0003-2501-0259 FU Intramural NIH HHS; Medical Research Council [G108/638] NR 15 TC 88 Z9 94 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2007 VL 39 IS 12 BP 1434 EP 1436 DI 10.1038/ng.2007.43 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 235XK UT WOS:000251267400008 PM 18037885 ER PT J AU Plenge, RM Cotsapas, C Davies, L Price, AL Bakker, PIW Maller, J Pe'er, I Burtt, NP Blumenstiel, B DeFelice, M Parkin, M Barry, R Winslow, W Healy, C Graham, RR Neale, BM Izmailova, E Roubenoff, R Parker, AN Glass, R Karlson, EW Maher, N Hafler, DA Lee, DM Seldin, MF Remmers, EF Lee, AT Padyukov, L Alfredsson, L Coblyn, J Weinblatt, ME Gabriel, SB Purcell, S Klareskog, L Gregersen, PK Shadick, NA Daly, MJ Altshuler, D AF Plenge, Robert M. Cotsapas, Chris Davies, Leela Price, Alkes L. Bakker, Paul I. Wde Maller, Julian Pe'er, Itsik Burtt, Noel P. Blumenstiel, Brendan DeFelice, Matt Parkin, Melissa Barry, Rachel Winslow, Wendy Healy, Claire Graham, Robert R. Neale, Benjamin M. Izmailova, Elena Roubenoff, Ronenn Parker, Alexander N. Glass, Roberta Karlson, Elizabeth W. Maher, Nancy Hafler, David A. Lee, David M. Seldin, Michael F. Remmers, Elaine F. Lee, Annette T. Padyukov, Leonid Alfredsson, Lars Coblyn, Jonathan Weinblatt, Michael E. Gabriel, Stacey B. Purcell, Shaun Klareskog, Lars Gregersen, Peter K. Shadick, Nancy A. Daly, Mark J. Altshuler, David TI Two independent alleles at 6q23 associated with risk of rheumatoid arthritis SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; GENETIC ASSOCIATION; POPULATION-STRUCTURE; STRATIFICATION; PROTEIN; VARIANT AB To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study(1). After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 ( rs10499194, similar to 150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association ( GWA) scan and in 5,541 additional case-control samples (P = 10(-3), GWA scan; P < 10(-6), replication; P = 10(-9), combined). In a concurrent study, the Wellcome Trust Case Control Consortium ( WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 ( rs6920220; P = 5 x 10(-6) in WTCCC)(2). We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23. C1 MIT, Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. Brigham & Womens Hosp, Harvard Med Sch, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02115 USA. Harvard Med Sch, Dept Genet, Boston, MA 02115 USA. Columbia Univ, Dept Comp Sci, New York, NY 10027 USA. Coll London, London SE5 8AF, England. Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Harvard Med Sch, Ctr Neurol Dis, Boston, MA 02115 USA. Univ Calif Davis, Rowe Program Genet, Davis, CA 95616 USA. NIAMSD, NIH, Genet Genom Branch, Bethesda, MD 20892 USA. N Shore Long Island Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. Karilinska Univ Hosp Solna, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. RP Plenge, RM (reprint author), MIT, Broad Inst Harvard, Program Med & Populat Genet, 77 Massachusetts Ave, Cambridge, MA 02142 USA. EM rplenge@partners.org RI Padyukov, Leonid/A-4890-2009; Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009; OI Cotsapas, Chris/0000-0002-7772-5910; Padyukov, Leonid/0000-0003-2950-5670; Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; Maller, Julian/0000-0002-1565-9559; Alfredsson, Lars/0000-0003-1688-6697; Healy, Claire M/0000-0001-7940-4611; Klareskog, Lars/0000-0001-9601-6186 FU NIAID NIH HHS [AI55314-3, K08 AI055314-01A1, K08 AI055314-02, K08 AI055314-03, K08 AI055314-04, K08 AI055314-05, K08 AI055314]; NIAMS NIH HHS [N01-AR-2-2263, R01 AR044422, R01-AR44422] NR 28 TC 371 Z9 380 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2007 VL 39 IS 12 BP 1477 EP 1482 DI 10.1038/ng.2007.27 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 235XK UT WOS:000251267400015 PM 17982456 ER PT J AU Myers, AJ Gibbs, JR AWebster, J Rohrer, K Zhao, A Marlowe, L Kaleem, M Leung, D Bryden, L Nath, P Zismann, VL Joshipura, K Huentelman, MJ Hu-Lince, D Coon, KD Craig, DW Pearson, JV Holmans, P Heward, CB Reiman, EM Stephan, D Hardy, J AF Myers, Amanda J. Gibbs, J. Raphael AWebster, Jennifer Rohrer, Kristen Zhao, Alice Marlowe, Lauren Kaleem, Mona Leung, Doris Bryden, Leslie Nath, Priti Zismann, Victoria L. Joshipura, Keta Huentelman, Matthew J. Hu-Lince, Diane Coon, Keith D. Craig, David W. Pearson, John V. Holmans, Peter Heward, Christopher B. Reiman, Eric M. Stephan, Dietrich Hardy, John TI A survey of genetic human cortical gene expression SO NATURE GENETICS LA English DT Article ID WHOLE-GENOME ASSOCIATION; MULTILOCUS GENOTYPE DATA; POPULATION-STRUCTURE; ALZHEIMERS-DISEASE; ALLELIC EXPRESSION; BRAIN; HAPLOTYPE; INFERENCE; MICE; APOE AB It is widely assumed that genetic differences in gene expression underpin much of the difference among individuals and many of the quantitative traits of interest to geneticists. Despite this, there has been little work on genetic variability in human gene expression and almost none in the human brain, because tools for assessing this genetic variability have not been available. Now, with whole-genome SNP genotyping arrays and whole-transcriptome expression arrays, such experiments have become feasible. We have carried out whole-genome genotyping and expression analysis on a series of 193 neuropathologically normal human brain samples using the Affymetrix GeneChip Human Mapping 500K Array Set and Illumina HumanRefseq-8 Expression BeadChip platforms. Here we present data showing that 58% of the transcriptome is cortically expressed in at least 5% of our samples and that of these cortically expressed transcripts, 21% have expression profiles that correlate with their genotype. These genetic-expression effects should be useful in determining the underlying biology of associations with common diseases of the human brain and in guiding the analysis of the genomic regions involved in the control of normal gene expression. C1 NIH, NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Univ Miami, Miller Sch Med, Dept Psychiat & Biobehav Sci, Div Neurosci, Miami, FL 33136 USA. Reta Lila Weston Inst, Neurol Inst, Dept Mol Neurosci & Neurodegenerat Dis, London WC1N 3BG, England. Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ 85004 USA. Arizona Alzheimers Consortium, Phoenix, AZ 85006 USA. St Josephs Hosp, Med Ctr, Div Thorac Oncol Res, Phoenix, AZ 85013 USA. Cardiff Univ, Dept Psychol Med, Bioinformat Unit, Cardiff CF14 4XN, Wales. Kronos Sci Lab, Phoenix, AZ 85016 USA. Banner Alzheimers Inst, Phoenix, AZ 85006 USA. RP Myers, AJ (reprint author), NIH, NIA, Neurogenet Lab, Bldg 10,Main Campus,Porter Neurosci Bldg, Bethesda, MD 20892 USA. EM amyers@med.miami.edu RI Myers, Amanda/B-1796-2010; Gibbs, J. Raphael/A-3984-2010; Hardy, John/C-2451-2009; Holmans, Peter/F-4518-2015; Pearson, John/F-2249-2011; Leung, Doris/R-5447-2016 OI Myers, Amanda/0000-0002-3100-9396; Holmans, Peter/0000-0003-0870-9412; Pearson, John/0000-0003-0904-4598; Leung, Doris/0000-0002-2558-7798 FU Medical Research Council [G9810900, G0701075]; NHLBI NIH HHS [UO1HL084744]; NIA NIH HHS [AG05144, AG05128, AG05146, AG10161, P30 AG19610, P30-AG13846, P50 AG05136, P50 AG16570, P50-AG08671, P50AG05681, U01 AG016976]; NIMH NIH HHS [MH60451]; NINDS NIH HHS [NS39764, U24NS051872] NR 20 TC 322 Z9 328 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2007 VL 39 IS 12 BP 1494 EP 1499 DI 10.1038/ng.2007.16 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 235XK UT WOS:000251267400018 PM 17982457 ER PT J AU Muse, GW Gilchrist, DA Nechaev, S Shah, R Parker, JS Grissom, SF Zeitlinger, J Adelman, K AF Muse, Ginger W. Gilchrist, Daniel A. Nechaev, Sergei Shah, Ruchir Parker, Joel S. Grissom, Sherry F. Zeitlinger, Julia Adelman, Karen TI RNA polymerase is poised for activation across the genome SO NATURE GENETICS LA English DT Article ID TRANSCRIPTION ELONGATION; IN-VIVO; DROSOPHILA-MELANOGASTER; HSP70 GENE; HEAT-SHOCK; PROMOTER; COMPLEX; CELLS; NELF; INITIATION AB Regulation of gene expression is integral to the development and survival of all organisms. Transcription begins with the assembly of a pre-initiation complex at the gene promoter(1), followed by initiation of RNA synthesis and the transition to productive elongation(2-4). In many cases, recruitment of RNA polymerase II ( Pol II) to a promoter is necessary and sufficient for activation of genes. However, there are a few notable exceptions to this paradigm, including heat shock genes and several proto-oncogenes, whose expression is attenuated by regulated stalling of polymerase elongation within the promoter-proximal region(5-13). To determine the importance of polymerase stalling for transcription regulation, we carried out a genome-wide search for Drosophila melanogaster genes with Pol II stalled within the promoter-proximal region. Our data show that stalling is widespread, occurring at hundreds of genes that respond to stimuli and developmental signals. This finding indicates a role for regulation of polymerase elongation in the transcriptional responses to dynamic environmental and developmental cues. C1 Natl Inst Hlth, Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Constella Grp, Durham, NC 27713 USA. Natl Inst Hlth, Natl Inst Environm Hlth Sci, Microarray Grp, Res Triangle Pk, NC 27709 USA. Express Anal, Durham, NC 27713 USA. Whitehead Inst Biomed Res, Nine Cambridge Ctr, Cambridge, MA 02142 USA. Stowers Inst Med Res, Kansas City, MO 64110 USA. RP Adelman, K (reprint author), Natl Inst Hlth, Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. EM adelmank@niehs.nih.gov OI Gilchrist, Daniel/0000-0003-1668-2790 FU Intramural NIH HHS [Z01 ES101987-02] NR 30 TC 440 Z9 444 U1 2 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2007 VL 39 IS 12 BP 1507 EP 1511 DI 10.1038/ng.2007.21 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 235XK UT WOS:000251267400020 PM 17994021 ER PT J AU Zeitlinger, J Stark, A Kellis, M Hong, JW Nechaev, S Adelman, K Levine, M Young, RA AF Zeitlinger, Julia Stark, Alexander Kellis, Manolis Hong, Joung-Woo Nechaev, Sergei Adelman, Karen Levine, Michael Young, Richard A. TI RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo SO NATURE GENETICS LA English DT Article ID TRANSCRIPTION ELONGATION; MESODERM DEVELOPMENT; PROXIMAL REGION; TARGET GENES; DORSAL; PROMOTER; EXPRESSION; PROTEIN; SNAIL; RECRUITMENT AB It is widely assumed that the key rate-limiting step in gene activation is the recruitment of RNA polymerase II ( Pol II) to the core promoter(1). Although there are well-documented examples in which Pol II is recruited to a gene but stalls(2-12), a general role for Pol II stalling in development has not been established. We have carried out comprehensive Pol II chromatin immunoprecipitation microarray ( ChIP-chip) assays in Drosophila embryos and identified three distinct Pol II binding behaviors: active ( uniform binding across the entire transcription unit), no binding, and stalled ( binding at the transcription start site). The notable feature of the similar to 10% genes that are stalled is that they are highly enriched for developmental control genes, which are either repressed or poised for activation during later stages of embryogenesis. We propose that Pol II stalling facilitates rapid temporal and spatial changes in gene activity during development. C1 Univ Calif Berkeley, Ctr Integrat Genom, Dept Mol Cell Biol, Berkeley, CA 94720 USA. Whitehead Inst Biomed Res, Nine Cambridge Ctr, Cambridge, MA 02142 USA. Broad Inst Massachustts Inst Technol & Harvard, Cambridge, MA 02141 USA. MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. NIH, Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Levine, M (reprint author), Univ Calif Berkeley, Ctr Integrat Genom, Dept Mol Cell Biol, Berkeley, CA 94720 USA. EM mlevine@berkeley.edu RI Stark, Alexander/D-1473-2012; Young, Richard/F-6495-2012 OI Stark, Alexander/0000-0003-2611-0841; Young, Richard/0000-0001-8855-8647 FU Intramural NIH HHS [Z01 ES101987-02]; NHGRI NIH HHS [HG002668, R01 HG002668, R01 HG004037, R01 HG004037-01A1]; NIGMS NIH HHS [GM069676, GM34431, R01 GM046638, R01 GM069676, R37 GM046638] NR 30 TC 429 Z9 435 U1 1 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2007 VL 39 IS 12 BP 1512 EP 1516 DI 10.1038/ng.2007.26 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 235XK UT WOS:000251267400021 PM 17994019 ER PT J AU Jankovic, D Trinchieri, G AF Jankovic, Dragana Trinchieri, Giorgio TI IL-10 or not IL-10: that is the question SO NATURE IMMUNOLOGY LA English DT Editorial Material ID T-CELLS; INTERLEUKIN-10; INFLAMMATION AB Four new papers focused on how interleukin 10-producing cells are induced have led to some unexpected and intriguing observations on the nature of interleukin 17-producing T helper cells. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, Tumor Immunobiol Sect, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Jankovic, D (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM trinchig@mail.nih.gov NR 9 TC 55 Z9 60 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2007 VL 8 IS 12 BP 1281 EP 1283 DI 10.1038/ni1207-1281 PG 3 WC Immunology SC Immunology GA 235XG UT WOS:000251267000005 PM 18026076 ER PT J AU Pandiyan, P Zheng, LX Ishihara, S Reed, J Lenardo, MJ AF Pandiyan, Pushpa Zheng, Lixin Ishihara, Satoru Reed, Jennifer Lenardo, Michael J. TI CD4(+) CD25(+) Foxp3(+) regulatory T cells induce cytokine deprivation -mediated apoptosis of effector CD4(+) T cells SO NATURE IMMUNOLOGY LA English DT Article ID IN-VIVO; INTESTINAL INFLAMMATION; DENDRITIC CELLS; CUTTING EDGE; SUPPRESSOR FUNCTION; AUTOIMMUNE-DISEASE; INTERLEUKIN-2; IL-2; ACTIVATION; DEATH AB A key issue in mammalian immunology is how CD4(+) CD25(+) Foxp3(+) regulatory T cells ( T-reg cells) suppress immune responses. Here we show that Treg cells induced apoptosis of effector CD4+ T cells in vitro and in vivo in a mouse model of inflammatory bowel disease. Treg cells did not affect the early activation or proliferation of effector CD4(+) T cells. Cytokines that signal through the common gamma- chain suppressed T-reg cell- induced apoptosis. T-reg cell-induced effector CD4(+) T cell death required the proapoptotic protein Bim, and effector CD4(+) T cells incubated with T-reg cells showed less activation of the prosurvival kinase Akt and less phosphorylation of the proapoptotic protein Bad. Thus, cytokine deprivation-induced apoptosis is a prominent mechanism by which T-reg cells inhibit effector T cell responses. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM lenardo@nih.gov FU Intramural NIH HHS NR 50 TC 518 Z9 541 U1 4 U2 35 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2007 VL 8 IS 12 BP 1353 EP 1362 DI 10.1038/ni1536 PG 10 WC Immunology SC Immunology GA 235XG UT WOS:000251267000016 PM 17982458 ER PT J AU Stumhofer, JS Silver, JS Laurence, A Porrett, PM Harris, TH Turka, LA Ernst, M Saris, CJM O'Shea, JJ Hunter, CA AF Stumhofer, Jason S. Silver, Jonathan S. Laurence, Arian Porrett, Paige M. Harris, Tajie H. Turka, Laurence A. Ernst, Matthias Saris, Christiaan J. M. O'Shea, John J. Hunter, Christopher A. TI Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10 SO NATURE IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; CYTOKINE PRODUCTION; REGULATORY FUNCTION; TOXOPLASMA-GONDII; TRYPANOSOMA-CRUZI; INTERFERON-GAMMA; AUTOIMMUNE ENCEPHALOMYELITIS; TRANSCRIPTION FACTOR; T(H)17 CELLS; IL-10 LOCUS AB Interleukin 10 (IL-10) has a prominent function in regulating the balance between protective and pathological T cell responses. Consistent with that activity, many sources of this cytokine are found in vivo, including from myeloid cells and a variety of T cell subsets. However, although there are many pathways that regulate innate production of IL-10, the factors that govern its synthesis by the adaptive response are poorly understood. Here we report that IL-27 and IL-6 induced T helper type 1 and type 2 cells, as well as T helper cells that produce IL-17, to secrete IL-10. This effect was dependent on the transcription factors STAT1 and STAT3 for IL-27 and on STAT3 for IL-6. Our studies identify a previously unknown pathway that allows the immune system to temper inflammatory responses. C1 Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Ludwig Inst Canc Res, Parkville, Vic 3050, Australia. Amgen Inc, Dept Inflammat Res, Thousand Oaks, CA 91320 USA. RP Hunter, CA (reprint author), Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. EM chunter@vet.upenn.edu RI Laurence, Arian/A-8770-2009; Ernst, Matthias/D-5111-2012; OI Laurence, Arian/0000-0003-0942-8292; Harris, Tajie/0000-0002-1355-2109 FU NIAID NIH HHS [AI 43620, AI41158, AI42334, 1-T32-AI-055428, 1-T32-AI-07532] NR 58 TC 435 Z9 456 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2007 VL 8 IS 12 BP 1363 EP U5 DI 10.1038/ni1537 PG 10 WC Immunology SC Immunology GA 235XG UT WOS:000251267000017 PM 17994025 ER PT J AU Wardenburg, JB Bae, T Otto, M Deleo, FR Schneewind, O AF Wardenburg, Juliane Bubeck Bae, Taeok Otto, Michael DeLeo, Frank R. Schneewind, Olaf TI Poring over pores: alpha-hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumonia SO NATURE MEDICINE LA English DT Letter ID NECROTIZING PNEUMONIA; SEQUENCE C1 Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. Indiana Univ, Sch Med, Dept Microbiol & Immunol, Gary, IN 46408 USA. NIH, NIAID, Rocky Mt Labs, Lab Human BActerial Pathogenesis, Hamilton, MT 59840 USA. RP Schneewind, O (reprint author), Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA. EM oschnee@bsd.uchicago.edu NR 9 TC 255 Z9 262 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD DEC PY 2007 VL 13 IS 12 BP 1405 EP 1406 DI 10.1038/nm1207-1405 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 238KB UT WOS:000251445400009 PM 18064027 ER PT J AU Tsai, YC Mendoza, A Mariano, JM Zhou, M Kostova, Z Chen, B Veenstra, T Hewitt, SM Helman, LJ Khanna, C Weissman, AM AF Tsai, Yien Che Mendoza, Arnulfo Mariano, Jennifer M. Zhou, Ming Kostova, Zlatka Chen, Bo Veenstra, Timothy Hewitt, Stephen M. Helman, Lee J. Khanna, Chand Weissman, Allan M. TI The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation SO NATURE MEDICINE LA English DT Article ID AUTOCRINE MOTILITY FACTOR; RETICULUM-ASSOCIATED DEGRADATION; FACTOR-RECEPTOR; ENDOPLASMIC-RETICULUM; SUPPRESSOR GENES; TETRASPANIN CD82; PROTEIN LIGASE; EXPRESSION; CELLS; IDENTIFICATION AB Metastasis is the primary cause of mortality from cancer, but the mechanisms leading to metastasis are poorly understood. In particular, relatively little is known about metastasis in cancers of mesenchymal origins, which are known as sarcomas. Approximately ten proteins have been characterized as 'metastasis suppressors', but how these proteins function and are regulated is, in general, not well understood. Gp78 (also known as AMFR or RNF45) is a RING finger E3 ubiquitin ligase that is integral to the endoplasmic reticulum (ER) and involved in ER-associated degradation (ERAD) of diverse substrates(1-6). Here we report that expression of gp78 has a causal role in the metastasis of an aggressive human sarcoma and that this prometastatic activity requires the E3 activity of gp78. Further, gp78 associates with and targets the transmembrane metastasis suppressor, KAI1 (also known as CD82), for degradation. Suppression of gp78 increases KAI1 abundance and reduces the metastatic potential of tumor cells, an effect that is largely blocked by concomitant suppression of KAI1. An inverse relationship between these proteins was confirmed in a human sarcoma tissue microarray. Whereas most previous efforts have focused on genetic mechanisms for the loss of metastasis suppressor genes, our results provide new evidence for post-translational downregulation of a metastasis suppressor by its ubiquitin ligase, resulting in abrogation of its metastasis suppressing effects. C1 NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Lab Protein Dynam & Signaling, Ctr Canc Res, NIH, Frederick, MD 21702 USA. NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA. NCI, Biomed Proteom Program, NIH, Frederick, MD 21702 USA. RP Khanna, C (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov; amw@nih.gov OI Hewitt, Stephen/0000-0001-8283-1788; Tsai, Yien Che/0000-0001-9624-1092 FU Intramural NIH HHS NR 27 TC 97 Z9 102 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2007 VL 13 IS 12 BP 1504 EP 1509 DI 10.1038/nm1686 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 238KB UT WOS:000251445400026 PM 18037895 ER PT J AU Wang, R Braughton, KR Kretschmer, D Bach, THL Queck, SY Li, M Kennedy, AD Dorward, DW Klebanoff, SJ Peschel, A Deleo, FR Otto, M AF Wang, Rong Braughton, Kevin R. Kretschmer, Dorothee Bach, Thanh-Huy L. Queck, Shu Y. Li, Min Kennedy, Adam D. Dorward, David W. Klebanoff, Seymour J. Peschel, Andreas DeLeo, Frank R. Otto, Michael TI Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA SO NATURE MEDICINE LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; PANTON-VALENTINE LEUKOCIDIN; NECROTIZING PNEUMONIA; GENOME; EPIDERMIDIS; EVOLUTION; STRAINS; INFECTIONS; INSIGHTS; DISEASE AB Methicillin-resistant Staphylococcus aureus (MRSA) remains a major human pathogen. Traditionally, MRSA infections occurred exclusively in hospitals and were limited to immunocompromised patients or individuals with predisposing risk factors. However, recently there has been an alarming epidemic caused by community-associated (CA)-MRSA strains, which can cause severe infections that can result in necrotizing fasciitis or even death in otherwise healthy adults outside of healthcare settings(1,2). In the US, CA-MRSA is now the cause of the majority of infections that result in trips to the emergency room(3). It is unclear what makes CA-MRSA strains more successful in causing human disease compared with their hospital-associated counterparts. Here we describe a class of secreted staphylococcal peptides that have a remarkable ability to recruit, activate and subsequently lyse human neutrophils, thus eliminating the main cellular defense against S. aureus infection. These peptides are produced at high concentrations by standard CA-MRSA strains and contribute significantly to the strains' ability to cause disease in animal models of infection. Our study reveals a previously uncharacterized set of S. aureus virulence factors that account at least in part for the enhanced virulence of CA-MRSA. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, US NIH, Hamilton, MT 59840 USA. Univ Tubingen, Cellular & Mol Microbiol Unit, Med Microbiol & Hyg Dept, D-72076 Tubingen, Germany. NIAID, Microscopy Unit, Res Technol Sect, Rocky Mt Labs,US NIH, Hamilton, MT 59840 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, US NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM motto@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS NR 27 TC 477 Z9 497 U1 5 U2 48 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2007 VL 13 IS 12 BP 1510 EP 1514 DI 10.1038/nm1656 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 238KB UT WOS:000251445400027 PM 17994102 ER PT J AU Nienborg, H Cumming, BG AF Nienborg, Hendrikje Cumming, Bruce G. TI Psychophysically measured task strategy for disparity discrimination is reflected in V2 neurons SO NATURE NEUROSCIENCE LA English DT Article ID FEATURE-BASED ATTENTION; MACAQUE VISUAL-CORTEX; AREA MT; DEPTH DISCRIMINATION; REVERSE-CORRELATION; APPARENT MOTION; CHOICE; MONKEY; PERCEPTION; RESPONSES AB In perceptual tasks, subjects attempt to rely on their most informative cues. Such strategic choices should be reflected in the types of sensory neurons that are used. We investigated this in a binocular-disparity discrimination task. Using psychophysical reverse-correlation, also known as image classification, we identified the perceptual strategies of two macaques (Macaca mulatta). Correlations between reported disparity signs and disparity noise samples for each trial yielded detection 'filters'. Filter amplitude was greater at near disparities than at far disparities, indicating that the subjects relied more on near disparities. Recordings from both macaques' disparity-selective V2 neurons showed a correlation between neuronal responses and perceptual judgment in near-preferring, but not far-preferring, units, mirroring the psychophysically measured strategy. After one monkey learned to weight near and far disparities equally, activity in its far-preferring neurons correlated with choice. Thus, the pattern of correlations between neuronal activity and perceptual reports indicates how subjects use their neuronal signals. C1 Natl Inst Hlth, NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Nienborg, H (reprint author), Natl Inst Hlth, NEI, Sensorimotor Res Lab, 49-2A50 Convent Dr, Bethesda, MD 20892 USA. EM hn@lsr.nei.nih.gov FU Intramural NIH HHS [Z01 EY000404-06, Z01 EY000404-07] NR 35 TC 25 Z9 26 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2007 VL 10 IS 12 BP 1608 EP 1614 DI 10.1038/nn1991 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 234OH UT WOS:000251172900019 PM 17965712 ER PT J AU Robinson, GW AF Robinson, Gertraud W. TI Cooperation of signalling pathways in embryonic mammary gland development SO NATURE REVIEWS GENETICS LA English DT Review ID HORMONE-RELATED PROTEIN; HYPOHIDROTIC ECTODERMAL DYSPLASIA; HAIR FOLLICLE DEVELOPMENT; BREAST DEVELOPMENT; TISSUE INTERACTION; ALTER LIMB; MOUSE; TBX3; EXPRESSION; DIFFERENTIATION AB Mammary glands become functional only in adult life but their development starts in the embryo. Initiation of the epithelial bud and ductal outgrowth are coordinated through short-range signals between epithelium and mesenchyme. Studies of natural and induced mouse mutants in which early mammary development is perturbed have identified genetic networks that regulate specific steps in these processes. Some of these signals contribute to aberrant mammary development in humans and are deregulated in cancer. C1 [Robinson, Gertraud W.] NIH, NIDDKD, Lab Genet & Physiol, Bethesda, MD 20892 USA. RP Robinson, GW (reprint author), NIH, NIDDKD, Lab Genet & Physiol, BLdg 8,Room 101,8 Ctr Dr, Bethesda, MD 20892 USA. EM traudl@nih.gov RI Robinson, Gertraud/I-2136-2012 FU Intramural NIH HHS NR 54 TC 60 Z9 61 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD DEC PY 2007 VL 8 IS 12 BP 963 EP 972 DI 10.1038/nrg2227 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 239XH UT WOS:000251551100015 PM 18007652 ER PT J AU Fujii, K Hurley, JH Freed, EO AF Fujii, Ken Hurley, James H. Freed, Eric O. TI Beyond Tsg101: the role of Alix in 'ESCRTing' HIV-1 SO NATURE REVIEWS MICROBIOLOGY LA English DT Article ID LATE-BUDDING DOMAINS; PLASMA-MEMBRANE; STRUCTURAL BASIS; ASSEMBLY DOMAIN; SORTING PATHWAY; VIRUS RELEASE; GAG PROTEIN; BINDING; TRAFFICKING; ALIX/AIP1 AB The limited coding capacity of retroviral genomes forces these viruses to rely heavily on the host-cell machinery for their replication. This phenomenon is particularly well illustrated by the interaction between retroviruses and components of the endosomal budding machinery that occurs during virus release. Here, we focus on the use of host-cell factors during HIV-1 budding and highlight recent progress in our understanding of the role of one such factor, Alix, in both viral and cellular membrane budding and fission events. C1 NCI, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21702 USA. NIH, Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, Bethesda, MD 20892 USA. RP Freed, EO (reprint author), NCI, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21702 USA. EM efreed@nih.gov FU Intramural NIH HHS NR 41 TC 94 Z9 97 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD DEC PY 2007 VL 5 IS 12 BP 912 EP 916 DI 10.1038/nrmicro1790 PG 5 WC Microbiology SC Microbiology GA 238AB UT WOS:000251417900011 PM 17982468 ER PT J AU Chumakov, K Ehrenfeld, E Wimmer, E Agol, VI AF Chumakov, Konstantin Ehrenfeld, Ellie Wimmer, Eckard Agol, Vadim I. TI Vaccination against polio should not be stopped SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID IMMUNODEFICIENT PATIENT; UNITED-STATES; OPV CESSATION; PARALYTIC POLIOMYELITIS; ATTENUATED POLIOVIRUS; ERADICATION; EVOLUTION; VIRUS; DISEASE; STRAIN AB The striking 50-year-long decline in the incidence of poliomyelitis has stalled in the past 7 years, which has led to calls for an urgent re-assessment of eradication and post-eradication campaign strategies. The current plan of eliminating the circulation of wild poliovirus so that further immunization will be unnecessary does not take into account recent scientific data and political realities that limit the likelihood that this strategy can sustain prevention of the disease. It is crucially important that high levels of population immunity are maintained against polio in the foreseeable future. C1 NIH, Natl Inst Allergy & Infect Dis, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. SUNY Stony Brook, Sch Med, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. Russian Acad Med Sci, Inst Poliomyelitis & Viral Encephalitis, Moscow 142782, Russia. RP Ehrenfeld, E (reprint author), NIH, Natl Inst Allergy & Infect Dis, Bldg 10, Bethesda, MD 20892 USA. EM eehrenfeld@niaid.nih.gov RI Agol, Vadim/E-1941-2013 FU Intramural NIH HHS NR 61 TC 43 Z9 46 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD DEC PY 2007 VL 5 IS 12 BP 952 EP U13 DI 10.1038/nrmicro1769 PG 7 WC Microbiology SC Microbiology GA 238AB UT WOS:000251417900015 PM 17965726 ER PT J AU Rampalli, S Li, L Mak, E Ge, K Brand, M Tapscott, SJ Dilworth, FJ AF Rampalli, Shravanti Li, LiFang Mak, Esther Ge, Kai Brand, Marjorie Tapscott, Stephen J. Dilworth, F. Jeffrey TI p38 MAPK signaling regulates recruitment of Ash2L-containing methyltransferase complexes to specific genes during differentiation SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID SKELETAL-MUSCLE DIFFERENTIATION; HISTONE H3; TRANSCRIPTION FACTOR; GROUP PROTEINS; MYOGENIN GENE; EXPRESSION; MOUSE; METHYLATION; TRITHORAX; BINDING AB Cell-specific patterns of gene expression are established through the antagonistic functions of trithorax group (TrxG) and Polycomb group (PcG) proteins. Several muscle-specific genes have previously been shown to be epigenetically marked for repression by PcG proteins in muscle progenitor cells. Here we demonstrate that these developmentally regulated genes become epigenetically marked for gene expression (trimethylated on histone H3 Lys4, H3K4me3) during muscle differentiation through specific recruitment of Ash2L-containing methyltransferase complexes. Targeting of Ash2L to specific genes is mediated by the transcriptional regulator Mef 2d. Furthermore, this interaction is modulated during differentiation through activation of the p38 MAPK signaling pathway via phosphorylation of Mef 2d. Thus, we provide evidence that signaling pathways regulate the targeting of TrxG-mediated epigenetic modifications at specific promoters during cellular differentiation. C1 Ottawa Hlth Res Inst, Sprott Ctr Stern Cell Res, Ottawa, ON K1H 8L6, Canada. NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8L6, Canada. Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA. RP Dilworth, FJ (reprint author), Ottawa Hlth Res Inst, Sprott Ctr Stern Cell Res, Ottawa, ON K1H 8L6, Canada. EM jdilworth@ohri.ca OI Ge, Kai/0000-0002-7442-5138 FU Intramural NIH HHS [Z01 DK075003-04, Z99 DK999999, Z01 DK047055-01]; NIDDK NIH HHS [ZIADK075003-06] NR 39 TC 128 Z9 130 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD DEC PY 2007 VL 14 IS 12 BP 1150 EP 1156 DI 10.1038/nsmb1316 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 237ZQ UT WOS:000251416500009 PM 18026121 ER PT J AU Wu, S Shi, YJ Mulligan, P Gay, F Landry, J Liu, HF Lu, J Qi, HH Wang, WJ Nickoloff, JA Wu, C Shi, Y AF Wu, Su Shi, Yujiang Mulligan, Peter Gay, Frederique Landry, Joseph Liu, Huifei Lu, Ju Qi, Hank H. Wang, Weijia Nickoloff, Jac A. Wu, Carl Shi, Yang TI A YY1-INO80 complex regulates genomic stability through homologous recombination-based repair SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID CHROMATIN REMODELING COMPLEX; PROMOTES BRANCH MIGRATION; ESCHERICHIA-COLI RUVA; STRAND BREAK REPAIR; DNA-BINDING PROTEIN; HOLLIDAY JUNCTIONS; S-PHASE; V(D)J RECOMBINATION; CANCER CONNECTION; TUMOR-SUPPRESSOR AB DNA damage repair is crucial for the maintenance of genome integrity and cancer suppression. We found that loss of the mouse transcription factor YY1 resulted in polyploidy and chromatid aberrations, which are signatures of defects in homologous recombination. Further biochemical analyses identified a YY1 complex comprising components of the evolutionarily conserved INO80 chromatin-remodeling complex. Notably, RNA interference-mediated knockdown of YY1 and INO80 increased cellular sensitivity toward DNA-damaging agents. Functional assays revealed that both YY1 and INO80 are essential in homologous recombination-based DNA repair (HRR), which was further supported by the finding that YY1 preferentially bound a recombination-intermediate structure in vitro. Collectively, these observations reveal a link between YY1 and INO80 and roles for both in HRR, providing new insight into mechanisms that control the cellular response to genotoxic stress. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Dept Mol & Cellular Biol, Program Neurosci, Cambridge, MA 02138 USA. Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. RP Shi, Y (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM yang_shi@hms.harvard.edu FU NIGMS NIH HHS [GM53874, R01 GM053874-15, R01 GM053874] NR 50 TC 99 Z9 111 U1 10 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD DEC PY 2007 VL 14 IS 12 BP 1165 EP 1172 DI 10.1038/nsmb1332 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 237ZQ UT WOS:000251416500011 PM 18026119 ER PT J AU Barnard, TJ Dautin, N Lukacik, P Bernstein, HD Buchanan, SK AF Barnard, Travis J. Dautin, Nathalie Lukacik, Petra Bernstein, Harris D. Buchanan, Susan K. TI Autotransporter structure reveals intra-barrel cleavage followed by conformational changes SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID GRAM-NEGATIVE BACTERIA; OUTER-MEMBRANE; ESCHERICHIA-COLI; PROTEIN SECRETION; SERINE-PROTEASE; TRANSLOCATOR DOMAIN; CRYSTAL-STRUCTURE; PASSENGER; PATHWAYS; ESPP AB Autotransporters are virulence factors produced by Gram-negative bacteria. They consist of two domains, an N-terminal 'passenger' domain and a C-terminal beta-domain. beta-domains form beta-barrel structures in the outer membrane while passenger domains are translocated into the extracellular space. In some autotransporters, the two domains are separated by proteolytic cleavage. Using X-ray crystallography, we solved the 2.7-angstrom structure of the post-cleavage state of the beta-domain of EspP, an autotransporter produced by Escherichia coli strain O157:H7. The structure consists of a 12-stranded beta-barrel with the passenger domain-beta-domain cleavage junction located inside the barrel pore, approximately midway between the extracellular and periplasmic surfaces of the outer membrane. The structure reveals an unprecedented intra-barrel cleavage mechanism and suggests that two conformational changes occur in the beta-domain after cleavage, one conferring increased stability on the beta-domain and another restricting access to the barrel pore. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. EM harris_bernstein@nih.gov; skbuchan@helix.nih.gov FU Intramural NIH HHS [Z01 DK036139-01] NR 42 TC 99 Z9 101 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD DEC PY 2007 VL 14 IS 12 BP 1214 EP 1220 DI 10.1038/nsmb1322 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 237ZQ UT WOS:000251416500018 PM 17994105 ER PT J AU Koyama, Y Barrett, T Hama, Y Ravizzini, G Choyke, PL Kobayashi, H AF Koyama, Yoshinori Barrett, Tristan Hama, Yukihiro Ravizzini, Gregory Choyke, Peter L. Kobayashi, Hisataka TI In vivo molecular imaging to diagnose and subtype tumors through receptor-targeted optically labeled monoclonal antibodies SO NEOPLASIA LA English DT Article DE growth factor receptor; optical imaging; contrast agent; near-infrared; antibody cocktail ID FLUORESCENT; IMMUNOHISTOCHEMISTRY; METASTASIS; PROTEIN; CANCER AB Molecular imaging of cell surface receptors can potentially diagnose tumors based on their distinct expression profiles. Using multifilter spectrally resolved optical imaging with three fluorescently labeled antibodies, we simultaneously imaged three different cell surface receptors to distinguish tumor types non-invasively. We selected tumors overexpressing different subtypes of EGFR receptor: HER-1 (A431) and HER-2 (NIH3T3/HER2(+)), or interleukin-2 receptor alpha-subunit receptor (IL-2R alpha;SP2/Tac). After tumor establishment, a cocktail of three fluorescently labeled monoclonal antibodies was injected: cetuximab-Cy5 ( targeting HER-1), trastuzumab - Cy7(HER-2), and daclizumab - AlexaFluor-700 (IL-2Ra). Optical fluorescence imaging was performed after 24 hours with both a red filter set and three successive filter sets ( yellow, red, and deep red). Spectrally resolved imaging of 10 mice clearly distinguished A431, NIH3T3/HER2(+), and SP2-Tac tumors based on their distinct optical spectra. Three-filter sets significantly increased the signal-to-background ratio compared to a single-filter set by reducing the background signal, thus significantly improving the differentiation of each of the receptors targeted ( P < .022). In conclusion, following multifilter spectrally resolved imaging, different tumor types can be simultaneously distinguished and diagnosed in vivo. Multiple filter sets increase the signal-to-noise ratio by substantially reducing the background signal, and may allow more optical dyes to be resolved within the narrow limits of the near-infrared spectrum. C1 NIH, Natl Canc Inst, Ctr Canc Res, Mol Imaging Program, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NIH, Natl Canc Inst, Ctr Canc Res, Mol Imaging Program, Bldg 10,Room 1B40, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU Intramural NIH HHS NR 19 TC 65 Z9 65 U1 2 U2 10 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD DEC PY 2007 VL 9 IS 12 BP 1021 EP 1029 DI 10.1593/neo.07787 PG 9 WC Oncology SC Oncology GA 238KL UT WOS:000251446400004 PM 18084609 ER PT J AU Soula, H Chow, CC AF Soula, Hedi Chow, Carson C. TI Stochastic dynamics of a finite-size spiking neural network SO NEURAL COMPUTATION LA English DT Article ID FIRE NEURONS; ASYNCHRONOUS STATES; WORKING-MEMORY; SYNAPTIC MECHANISMS; PERSISTENT ACTIVITY; INHIBITORY NEURONS; CORTEX; SYNCHRONY; INTEGRATION; AVALANCHES AB We present a simple Markov model of spiking neural dynamics that can be analytically solved to characterize the stochastic dynamics of a finite-size spiking neural network. We give closed-form estimates for the equilibrium distribution, mean rate, variance, and autocorrelation function of the network activity. The model is applicable to any network where the probability of firing of a neuron in the network depends on only the number of neurons that fired in a previous temporal epoch. Networks with statistically homogeneous connectivity and membrane and synaptic time constants that are not excessively long could satisfy these conditions. Our model completely accounts for the size of the network and correlations in the firing activity. It also allows us to examine how the network dynamics can deviate from mean field theory. We show that the model and solutions are applicable to spiking neural networks in biophysically plausible parameter regimes. C1 NIDDK, Lab Biol Modelling, NIH, Bethesda, MD 20892 USA. RP Soula, H (reprint author), NIDDK, Lab Biol Modelling, NIH, Bethesda, MD 20892 USA. EM hedi.soula@insa-lyon.fr; carsonc@mail.nih.gov RI Chow, Carson/A-7970-2009 FU Intramural NIH HHS NR 40 TC 22 Z9 22 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA SN 0899-7667 J9 NEURAL COMPUT JI Neural Comput. PD DEC PY 2007 VL 19 IS 12 BP 3262 EP 3292 DI 10.1162/neco.2007.19.12.3262 PG 31 WC Computer Science, Artificial Intelligence SC Computer Science GA 228SE UT WOS:000250751900006 PM 17970653 ER PT J AU Honson, NS Johnson, RL Huang, WW Inglese, J Austin, CP Kuret, J AF Honson, Nicolette S. Johnson, Ronald L. Huang, Wenwei Inglese, James Austin, Christopher P. Kuret, Jeff TI Differentiating Alzheimer disease-associated aggregates with small molecules SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Alzheimer disease; tau; neurofibrillary tangle; contrast agents; diagnosis ID PAIRED HELICAL FILAMENTS; FIBRILLIZATION IN-VITRO; PITTSBURGH COMPOUND-B; BETA-AMYLOID FIBRILS; ALPHA-SYNUCLEIN; COGNITIVE IMPAIRMENT; TAU-FIBRILLIZATION; IMAGING AGENTS; THIOFLAVIN-T; PROTEIN-TAU AB Alzheimer disease is diagnosed postmortem by the density and spatial distribution of beta-amyloid plaques and tau-bearing neurofibrillary tangles. The major protein component of each lesion adopts cross-beta-sheet conformation capable of binding small molecules with submicromolar affinity. In many cases, however, Alzheimer pathology overlaps with Lewy body disease, characterized by the accumulation of a third cross-beta-sheet forming protein, alpha-synuclein. To determine the feasibility of distinguishing tau aggregates from beta-amyloid and alpha-synuclein aggregates with small molecule probes, a library containing 72,455 small molecules was screened for antagonists of tau-aggregate-mediated changes in Thioflavin S fluorescence, followed by secondary screens to distinguish the relative affinity for each substrate protein. Results showed that >10-fold binding selectivity among substrates could be achieved, with molecules selective for tau aggregates containing at least three aromatic or rigid moieties connected by two rotatable bonds. (C) 2007 Elsevier Inc. All rights reserved. C1 [Honson, Nicolette S.; Kuret, Jeff] Ohio State Univ, Ctr Mol Neurobiol, Columbus, OH 43210 USA. [Johnson, Ronald L.; Huang, Wenwei; Inglese, James; Austin, Christopher P.] NIH, Chem Gen Ctr, Rockville, MD 20850 USA. RP Kuret, J (reprint author), Ohio State Univ, Ctr Mol Neurobiol, 1060 Carmack Rd, Columbus, OH 43210 USA. EM kuret.3@osu.edu FU Intramural NIH HHS; NIA NIH HHS [AG14452, R01 AG014452-07, R01 AG014452]; NIMH NIH HHS [MH077621] NR 48 TC 32 Z9 32 U1 3 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD DEC PY 2007 VL 28 IS 3 BP 251 EP 260 DI 10.1016/j.nbd.2007.07.018 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 242TT UT WOS:000251749800002 PM 17761424 ER PT J AU Kriegeskorte, N Bandettini, P AF Kriegeskorte, Nikolaus Bandettini, Peter TI Analyzing for information, not activation, to exploit high-resolution fMRI SO NEUROIMAGE LA English DT Editorial Material ID FALSE DISCOVERY RATE; FUSIFORM FACE AREA; VISUAL-CORTEX; HUMAN BRAIN; PHYSIOLOGICAL NOISE; CORTICAL SURFACE; OCULAR DOMINANCE; MAGNETIC-FIELDS; PATTERNS; SIGNAL AB High-resolution functional magnetic resonance imaging (hi-res fMRI) promises to help bridge the gap between the macro- and the microview of brain function afforded by conventional neuroimaging and invasive cell recording, respectively. Hi-res fMRI (voxel volume:5 (2 MM)3) is robustly achievable in human studies today using widely available clinical 3-Tesla scanners. However, the neuroscientific exploitation of the greater spatial detail poses four challenges: (1) Hi-res fMRI may give inaccurate (i.e. blurred, displaced and distorted) images of fine-scale neuronal activity patterns. (2) Single small voxels yield very noisy measurements. (3) The greater number of voxels complicates interpretation and poses a more severe multiple-comparisons problem. (4) The functional correspondency mapping between individual brains is unknown at the fine scale of millimeters. Here we argue that these challenges can be met by shifting the focus of brain mapping and visualizing, not the activity patterns themselves, but the amount of information they convey about the experimental conditions. Published by Elsevier Inc. C1 NIH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Kriegeskorte, N (reprint author), NIH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM kriegeskorten@mail.nih.gov RI Bandettini, Peter/F-5871-2012; OI Kriegeskorte, Nikolaus/0000-0001-7433-9005 FU Intramural NIH HHS [NIH0011638520]; PHS HHS [NIH0011638520] NR 67 TC 112 Z9 114 U1 1 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2007 VL 38 IS 4 BP 649 EP 662 DI 10.1016/j.neuroimage.2007.02.022 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 232MH UT WOS:000251023300001 PM 17804260 ER PT J AU Kriegeskorte, N Bandettini, P AF Kriegeskorte, Nikolaus Bandettini, Peter TI Combining the tools: Activation- and information-based fMRI analysis SO NEUROIMAGE LA English DT Editorial Material ID FUNCTIONAL LOCALIZERS; BRAIN C1 NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Kriegeskorte, N (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM kriegeskorten@mail.nih.gov RI Bandettini, Peter/F-5871-2012; OI Kriegeskorte, Nikolaus/0000-0001-7433-9005 NR 9 TC 27 Z9 28 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2007 VL 38 IS 4 BP 666 EP 668 DI 10.1016/j.neuroimage.2007.06.030 PG 3 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 232MH UT WOS:000251023300003 PM 17976583 ER PT J AU Trivedi, MH Rush, AJ Gaynes, BN Stewart, JW Wisniewski, SR Warden, D Ritz, L Luther, JF Stegman, D Deveaugh-Geiss, J Howland, R AF Trivedi, Madhukar H. Rush, A. John Gaynes, Bradley N. Stewart, Jonathan W. Wisniewski, Stephen R. Warden, Diane Ritz, Louise Luther, James F. Stegman, Diane Deveaugh-Geiss, Joanne Howland, Robert TI Maximizing the adequacy of medication treatment in controlled trials and clinical practice: STAR*D measurement-based care SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE depression algorithm; physician decision support; symptom monitoring; adequate antidepressant treatment; maximizing pharmacotherapy ID SEQUENCED TREATMENT ALTERNATIVES; MAJOR DEPRESSIVE DISORDER; RANDOMIZED CONTROLLED TRIAL; REPORT QIDS-SR; PRACTICE GUIDELINES; COLLABORATIVE CARE; PSYCHOMETRIC EVALUATION; ANTIDEPRESSANT USE; ALGORITHM PROJECT; QUICK INVENTORY AB The success of well-developed protocols has been limited in real-world practice, where even effective strategies have not been sufficient to meet patient needs in routine clinical care owing to Axis I and III comorbidities. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial required that antidepressant medication treatment be optimal regarding dose and duration, yet accommodate flexibility to ensure safety given the wide range of comorbid general medical and psychiatric disorders allowed in the trial. The objective of this study was to develop a measurement-based care (MBC) approach and an automated feedback system to ensure adequate and safe antidepressant treatment delivery suitable for both clinical research and routine practice. Ratings of depressive symptom severity and side-effect frequency, intensity, and burden were obtained at each treatment visit using the MBC system that (1) guided medication dose adjustments and treatment duration, (2) documented clinician adherence to treatment recommendations, and (3) provided prompt feedback to clinicians to enhance appropriate treatment decisions. Physician adherence to protocol-specific treatment was monitored based on measured symptoms and side-effect burden, and dose and duration of antidepressant at each critical decision point during the acute phase treatment of major depression. Feedback was provided at the point of care by the clinical coordinators, assisted by Web-based reports following each treatment visit. On the basis of the first treatment step with citalopram, over 85% of treatment encounters had appropriate fidelity to recommendations. Most deviations from treatment recommendations occurred late in treatment and were often justifiable. MBC proved to be feasible and effective in busy primary and psychiatric settings. This approach signals a paradigm shift toward the use of measurement-based clinical decisions, both at the point of care and following each visit, to deliver optimal pharmacotherapy for depression. C1 SW Texas State Univ, Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. Univ Pittsburgh, Sch Med, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. NIMH, Bethesda, MD USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. RP Trivedi, MH (reprint author), SW Texas State Univ, Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM madhukar.trivedi@utsouthwestern.edu RI Howland, Robert/K-6937-2015; OI Howland, Robert/0000-0002-6533-6010; Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003, 5R01MH064062-2, 5R01MH067692-2] NR 64 TC 81 Z9 83 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2007 VL 32 IS 12 BP 2479 EP 2489 DI 10.1038/sj.npp.1301390 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 231NS UT WOS:000250956000004 PM 17406651 ER PT J AU Wendland, JR Kruse, MR Cromer, KC Murphy, DL AF Wendland, Jens R. Kruse, Matthew R. Cromer, Kiara C. Murphy, Dennis L. TI A large case-control study of common functional SLC6A4 and BDNF variants in obsessive-compulsive disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE 5-HTT; psychiatric genetics; serotonin transporter; SERT ID SEROTONIN TRANSPORTER GENE; AGE-OF-ONSET; SYMPTOM DIMENSIONS; VARIABLE-NUMBER; TANDEM-REPEAT; TRANSMISSION DISEQUILIBRIUM; POLYMORPHISM 5-HTTLPR; PROMOTER POLYMORPHISM; REGION POLYMORPHISM; PERSONALITY-TRAITS AB Both serotonin transporter (SLC6A4) and brain-derived neurotrophic factor (BDNF) genes have shown positive associations with obsessive-compulsive disorder (OCD) and some other psychiatric disorders, but these results have not been consistently replicated. To explore the hypothesis that this variability might result from the effects of differing combinations of overlooked variants within SLC6A4 together with small OCD and control sample sizes, we studied three common functional polymorphisms (5-HTTLPR, STin2, and the newly discovered SNP, rs25531) in the largest sample size of OCD patients (N = 347) and controls (N = 749) ever investigated. During methods development, we found evidence for potential SLC6A4 genotyping problems with earlier methodology, a third possible contributor to variability in earlier studies. A fourth possible explanation might be SLC6A4 x BDNF interactions, which prompted us to investigate combined genotypes of BDNF V66M with the three SLC6A4 loci. Except for a nominal association with rs25531 alone, which did not survive correction for multiple comparisons, we found no evidence for any of these other variants being associated alone or together with OCD, and we therefore also examined clinical OCD subtypes within the sample to evaluate clinical heterogeneity. Subgroups based on the age of OCD onset, gender, familiality, factor analysis-derived symptom dimensions, or comorbidity with other psychiatric disorders failed to identify SLC6A4- or BDNF-associated phenotypes, with one exception of overall number of comorbid anxiety disorders being significantly associated with 5-HTTLPR/rs25531. We conclude that despite their attractiveness as candidate genes in OCD, our data provide no support for association in this large OCD patient sample and point toward the need to examine other genes as candidates for risk determinants in OCD. C1 NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. RP Wendland, JR (reprint author), NIMH, Clin Sci Lab, 10 Ctr Dr,MSC 1264,Bldg 10,3D41, Bethesda, MD 20892 USA. EM wendlandj@mail.nih.gov RI Wendland, Jens/A-1809-2012; Timpano, Kiara/C-8760-2012 FU Intramural NIH HHS NR 75 TC 53 Z9 58 U1 6 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2007 VL 32 IS 12 BP 2543 EP 2551 DI 10.1038/sj.npp.1301394 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 231NS UT WOS:000250956000010 PM 17375136 ER PT J AU Anandatheerthavarada, HK Devi, L AF Anandatheerthavarada, Hindupur K. Devi, Latha TI Amyloid precursor protein and mitochondrial dysfunction in Alzheimer's disease SO NEUROSCIENTIST LA English DT Article DE Alzheimer's disease; mitochondrial dysfunction; amyloid precursor protein; A beta; acidic domain; mitochondria; translocational arrest; import channels; transgenic mouse models ID CYTOCHROME-C-OXIDASE; A-BETA ACCUMULATION; NEURODEGENERATIVE DISEASES; OXIDATIVE STRESS; MEDIATED PHOSPHORYLATION; IN-VITRO; BRAIN; NEURONS; ACTIVATION; ASTROCYTES AB Growing evidence suggests that mitochondrial dysfunction is one of the key intracellular lesions associated with the pathogenesis of Alzheimer's disease (AD). Mitochondria, the powerhouses of the cell, participate in a number of physiological functions that include calcium homeostasis, signal transduction, and apoptosis. However, the pathophysiological mechanisms underlying the decline of mitochondrial vital functions leading to the dysfunction of mitochondria during AD are not well understood. Recent literature has observed the accumulation of Alzheimer's amyloid precursor protein (APP) and its C-terminal-cleaved product beta-amyloid (A beta) in the mitochondrial compartment. Furthermore, evidence also implicates that the accumulation of full-length APP and A beta in the mitochondrial compartment has a causative role in impairing mitochondrial physiological functions. Here, we review the mode of mitochondrial transport of full-length APP and A beta and its pathological implications in bringing about mitochondrial dysfunction as seen in AD. C1 Univ Penn, Sch Vet Med, NIH, NIA,Dept Anim Biol, Philadelphia, PA 19104 USA. RP Anandatheerthavarada, HK (reprint author), Univ Penn, Sch Vet Med, NIH, NIA,Dept Anim Biol, 3800 Spruce St,Rm 189E, Philadelphia, PA 19104 USA. EM ann1234@vet.upenn.edu FU NIA NIH HHS [AG 021920] NR 70 TC 45 Z9 48 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD DEC PY 2007 VL 13 IS 6 BP 626 EP 638 DI 10.1177/1073858407303536 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 233BR UT WOS:000251065900013 PM 17911214 ER PT J AU Iwatani, Y Chan, DSB Wang, F Maynard, KS Sugiura, W Gronenborn, AM Rouzina, I Williams, MC Musier-Forsyth, K Levin, JG AF Iwatani, Yasumasa Chan, Denise S. B. Wang, F. Maynard, Kristen Stewart Sugiura, Wataru Gronenborn, Angela M. Rouzina, Ioulia Williams, Mark C. Musier-Forsyth, Karin Levin, Judith G. TI Deaminase-independent inhibition of HIV-1 reverse transcription by APOBEC3G SO NUCLEIC ACIDS RESEARCH LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MINUS-STRAND TRANSFER; ACID-CHAPERONE ACTIVITY; VIRAL-DNA SYNTHESIS; NUCLEOCAPSID PROTEIN; ANTIVIRAL ACTIVITY; MURINE LEUKEMIA; VIF PROTEIN; NONPERMISSIVE CELLS; POLYPURINE TRACT AB APOBEC3G (A3G), a host protein that inhibits HIV-1 reverse transcription and replication in the absence of Vif, displays cytidine deaminase and single-stranded (ss) nucleic acid binding activities. HIV-1 nucleocapsid protein (NC) also binds nucleic acids and has a unique property, nucleic acid chaperone activity, which is crucial for efficient reverse transcription. Here we report the interplay between A3G, NC and reverse transcriptase (RT) and the effect of highly purified A3G on individual reactions that occur during reverse transcription. We find that A3G did not affect the kinetics of NC-mediated annealing reactions, nor did it inhibit RNase H cleavage. In sharp contrast, A3G significantly inhibited all RT-catalyzed DNA elongation reactions with or without NC. In the case of (-) strong-stop DNA synthesis, the inhibition was independent of A3Gs catalytic activity. Fluorescence anisotropy and single molecule DNA stretching analyses indicated that NC has a higher nucleic acid binding affinity than A3G, but more importantly, displays faster association/disassociation kinetics. RT binds to ssDNA with a much lower affinity than either NC or A3G. These data support a novel mechanism for deaminase-independent inhibition of reverse transcription that is determined by critical differences in the nucleic acid binding properties of A3G, NC and RT. C1 [Iwatani, Yasumasa; Levin, Judith G.] NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. [Iwatani, Yasumasa; Sugiura, Wataru] Natl Inst Infect Dis, AIDS Res Ctr, Tokyo 2080013, Japan. [Chan, Denise S. B.; Gronenborn, Angela M.] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA. [Wang, F.; Williams, Mark C.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Maynard, Kristen Stewart; Musier-Forsyth, Karin] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. [Rouzina, Ioulia] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. [Musier-Forsyth, Karin] Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. [Musier-Forsyth, Karin] Ohio State Univ, Dept Biochem, Columbus, OH 43210 USA. RP Levin, JG (reprint author), NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM levinju@mail.nih.gov OI Williams, Mark C./0000-0003-3219-376X; Gronenborn, Angela M/0000-0001-9072-3525 FU Intramural NIH HHS; NIGMS NIH HHS [GM072462, F32 GM072396, GM065056, R01 GM065056, R01 GM072462] NR 73 TC 164 Z9 168 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC PY 2007 VL 35 IS 21 BP 7096 EP 7108 DI 10.1093/nar/gkm750 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244MA UT WOS:000251868800016 PM 17942420 ER PT J AU Renaud, S Pugacheva, EM Delgado, MD Braunschweig, R Abdullaev, Z Loukinov, D Benhattar, J Lobanenkov, V AF Renaud, Stephanie Pugacheva, Elena M. Delgado, M. Dolores Braunschweig, Richard Abdullaev, Ziedulla Loukinov, Dmitri Benhattar, Jean Lobanenkov, Victor TI Expression of the CTCF-paralogous cancer-testis gene, brother of the regulator of imprinted sites (BORIS), is regulated by three alternative promoters modulated by CpG methylation and by CTCF and p53 transcription factors SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MESSENGER-RNA STABILITY; X-INACTIVATION CHOICE; TUMOR-SUPPRESSOR; ENHANCER-BLOCKING; DNA METHYLATION; DOWN-REGULATION; REGION; BINDING; CELLS; INSULATOR AB BORIS, like other members of the cancer/testis antigen family, is normally expressed in testicular germ cells and repressed in somatic cells, but is aberrantly activated in cancers. To understand regulatory mechanisms governing human BORIS expression, we characterized its 5-flanking region. Using 5 RACE, we identified three promoters, designated A, B and C, corresponding to transcription start sites at 1447, 899 and 658 bp upstream of the first ATG. Alternative promoter usage generated at least five alternatively spliced BORIS mRNAs with different half-lives determined by varying 5-UTRs. In normal testis, BORIS is transcribed from all three promoters, but 84 of the 30 cancer cell lines tested used only promoter(s) A and/or C while the others utilized primarily promoters B and C. The differences in promoter usage between normal and cancer cells suggested that they were subject to differential regulation. We found that DNA methylation and functional p53 contributes to the negative regulation of each promoter. Moreover, reduction of CTCF in normally BORIS-negative human fibroblasts resulted in derepression of BORIS promoters. These results provide a mechanistic basis for understanding cancer-related associations between haploinsufficiency of CTCF and BORIS derepression, and between the lack of functional p53 and aberrant activation of BORIS. C1 [Braunschweig, Richard; Benhattar, Jean] CHU Vaudois, Inst Pathol, CH-1011 Lausanne, Switzerland. [Renaud, Stephanie; Pugacheva, Elena M.; Abdullaev, Ziedulla; Loukinov, Dmitri; Lobanenkov, Victor] NIH, NIAID, Immunopathol Lab, Sect Mol Pathol, Rockville, MD 20815 USA. [Delgado, M. Dolores] Univ Cantabria, CSIC, Dept Mol Biol, Unida Biomed, E-39011 Santander, Spain. RP Benhattar, J (reprint author), CHU Vaudois, Inst Pathol, CH-1011 Lausanne, Switzerland. EM jean.benhattar@chuv.ch; vlobanenkov@niaid.nih.gov OI Lobanenkov, Victor/0000-0001-6665-3635 FU Intramural NIH HHS NR 62 TC 48 Z9 50 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC PY 2007 VL 35 IS 21 BP 7372 EP 7388 DI 10.1093/nar/gkm896 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244MA UT WOS:000251868800040 PM 17962299 ER PT J AU Brosh, RM Bohr, VA AF Brosh, Robert M., Jr. Bohr, Vilhelm A. TI Human premature aging, DNA repair and RecQ helicases SO NUCLEIC ACIDS RESEARCH LA English DT Review ID WERNER-SYNDROME PROTEIN; BLOOMS-SYNDROME HELICASE; SYNDROME GENE-PRODUCT; ROTHMUND-THOMSON-SYNDROME; G-QUADRUPLEX DNA; STRAND-ANNEALING ACTIVITIES; DAMAGED REPLICATION FORKS; TOPOISOMERASE III-ALPHA; BASE EXCISION-REPAIR; FUNCTIONAL INTERACTION AB Genomic instability leads to mutations, cellular dysfunction and aberrant phenotypes at the tissue and organism levels. A number of mechanisms have evolved to cope with endogenous or exogenous stress to prevent chromosomal instability and maintain cellular homeostasis. DNA helicases play important roles in the DNA damage response. The RecQ family of DNA helicases is of particular interest since several human RecQ helicases are defective in diseases associated with premature aging and cancer. In this review, we will provide an update on our understanding of the specific roles of human RecQ helicases in the maintenance of genomic stability through their catalytic activities and protein interactions in various pathways of cellular nucleic acid metabolism with an emphasis on DNA replication and repair. We will also discuss the clinical features of the premature aging disorders associated with RecQ helicase deficiencies and how they relate to the molecular defects. C1 [Brosh, Robert M., Jr.; Bohr, Vilhelm A.] NIH, Natl Inst Aging, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIH, Natl Inst Aging, Lab Mol Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov NR 192 TC 113 Z9 114 U1 2 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC PY 2007 VL 35 IS 22 BP 7527 EP 7544 DI 10.1093/nar/gkm1008 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 248BI UT WOS:000252125900017 PM 18006573 ER PT J AU Manolio, TA AF Manolio, Teri A. TI Study designs to in healthy aging SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT Conference on Living Well to 100 - Is Inflammation Central to Aging CY NOV, 2006 CL Tufts Univ, Boston, MA HO Tufts Univ DE healthy aging; complex trait; genetic association; familial; trait; candidate gene; genome-wide association ID COMPLEX HUMAN-DISEASES; LINKAGE DISEQUILIBRIUM; EPIDEMIOLOGIC RESEARCH; MACULAR DEGENERATION; EMERGING IMPORTANCE; RELATIVE POWER; FACTOR-H; LONGEVITY; POLYMORPHISM; ASSOCIATION AB The sequencing of the human genome and the growing understanding of its function are providing powerful new research tools for identifying genetic variants that are associated with complex diseases and traits. Somewhat less emphasis has been given to genes related to healthy aging, although the approaches for studying health-related traits are analogous to those used for disease-related studies. A critical step prior to the design of such studies is to define a healthy aging phenotype, which should be standardized to permit comparisons across studies and should involve more than simple longevity. Phenotypes of particular value for genetic research are those with high heritability and close relationships to gene products or pathways, preferably with minimal or at least measurable environmental influences. Appropriate study designs to identify genotype-phenotype associations include family-based linkage studies, candidate gene association analyses, and genome-wide association studies. Advances in genotyping and sequencing technologies, and the generation of the human haplotype map database, now permit the cost-effective investigation of the very large sample sizes needed for genome-wide association studies in unrelated individuals. Challenges in interpretation and translation of such studies include assessing the potential for bias and confounding, as well as determining the clinical validity and utility of findings proposed for wider application. Many such studies are currently supported or being planned across the National Institutes of Health (NIH), and lend themselves to the kind of coordinated clinical research envisioned in programs such as the NIH Roadmap. C1 [Manolio, Teri A.] NHGRI, NIH, Off Populat Genom, Bethesda, MD 20892 USA. RP Manolio, TA (reprint author), NHGRI, NIH, Off Populat Genom, Bldg 31,Room 4B-09,31 Ctr Dr,Mail Stop Code 2154, Bethesda, MD 20892 USA. EM manolio@nih.gov NR 28 TC 6 Z9 6 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD DEC PY 2007 VL 65 IS 12 BP S228 EP S233 DI 10.1301/nr.2007.dec.S228-S233 PN 2 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 245FL UT WOS:000251920400018 PM 18240554 ER PT J AU Romero, R Gotsch, F Pineles, B Kusanovic, JP AF Romero, Roberto Gotsch, Francesca Pineles, Beth Kusanovic, Juan Pedro TI Inflammation in pregnancy: Its roles in reproductive physiology, obstetrical complications, and fetal injury SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT Conference on Living Well to 100 - Is Inflammation Central to Aging CY NOV, 2006 CL Tufts Univ, Boston, MA HO Tufts Univ DE interleukin; preeclampsia; preterm parturition; tumor necrosis factor ID PRETERM PREMATURE RUPTURE; BIRTH-WEIGHT INFANTS; CEREBRAL-PALSY; RESPONSE SYNDROME; INTRAAMNIOTIC INFECTION; MATERNAL INFECTION; THYMIC INVOLUTION; RHESUS-MONKEYS; BRAIN-DAMAGE; LABOR AB Fetal development and growth occur in a sterile amniotic cavity while first exposure to microorganisms happens at birth. However, at least 25% of all preterm births, the leading cause of perinatal morbidity and mortality worldwide, occur in mothers with microbial invasion of the amniotic cavity. Microbial attack of the fetus takes place in approximately 10% of pregnancies with intra-amniotic infection, and the human fetus is capable of deploying an inflammatory response (cellular and humoral) in the mid-trimester of pregnancy. The onset of premature labor in the context of infection is mediated by pro-inflammatory cytokines, such as interleukin (IL)-1 beta and tumor necrosis factor alpha (TNF-alpha), as these cytokines are produced by intrauterine tissues in response to microbial products, can stimulate prostaglandin production, and induce labor in animals. Moreover, knockout experiments suggest that infection is less likely to lead to premature labor when the IL-1 and TNF signaling pathways are disrupted. A fetal inflammatory systemic response occurs in a fraction of fetuses exposed to microorganisms in utero, and is associated with the impending onset of labor as well as multi-system organ involvement. Neonates born with funisitis, the histologic marker of such inflammation, are at increased risk for neurologic handicap and cerebral palsy. Evidence has begun to accumulate that gene-environment interactions determine the likelihood of preterm labor and delivery and, probably, the risk of fetal injury. Fetal inflammation has emerged as a major mechanism of disease responsible for complications in the perinatal period (in utero and in the first 28 days of life), as well as in infancy. Moreover, reprogramming of the fetal immune response may predispose to diseases in adulthood. C1 [Romero, Roberto] NICHD, Hutzel Womens Hosp, NIH, DHHS,Perinatol Res Branch, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. NICHD, NIH, DHHS, Perinatol Res Branch, Bethesda, MD USA. NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. RP Romero, R (reprint author), NICHD, Hutzel Womens Hosp, NIH, DHHS,Perinatol Res Branch, Box 4,3990 John R Rd, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov FU Intramural NIH HHS NR 47 TC 167 Z9 176 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD DEC PY 2007 VL 65 IS 12 BP S194 EP S202 DI 10.1301/nr.2007.dec.S194-S202 PN 2 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 245FL UT WOS:000251920400012 PM 18240548 ER PT J AU Koster, A Penninx, BWJH Newman, AB Visser, M van Gool, CH Harris, TB van Eijk, JTM Kempen, GIJM Brach, JS Simonsick, EM Houston, DK Tylavsky, FA Rubin, SM Kritchevsky, SB AF Koster, Annemarie Penninx, Brenda W. J. H. Newman, Anne B. Visser, Marjolein van Gool, Coen H. Harris, Tamara B. van Eijk, Jacques Th. M. Kempen, Gertrudis I. J. M. Brach, Jennifer S. Simonsick, Eleanor M. Houston, Denise K. Tylavsky, Frances A. Rubin, Susan M. Kritchevsky, Stephen B. TI Lifestyle factors and incident mobility limitation in obese and non-obese older adults SO OBESITY LA English DT Article DE aging; lifestyles; smoking; physical activity ID CORONARY-HEART-DISEASE; BODY-MASS INDEX; PHYSICAL-ACTIVITY; RISK-FACTORS; HEALTH-STATUS; NHANES-I; SMOKING; PREVALENCE; OVERWEIGHT; MORTALITY AB Objective: This study examines the association between incident mobility limitation and 4 lifestyle factors: smoking, alcohol intake, physical activity, and diet in well-functioning obese (n = 667) and non-obese (n = 2027) older adults. Research Methods and Procedures: Data were from men and women, 70 to 79 years of age from Pittsburgh, PA and Memphis, TN, participating in the Health, Aging and Body Composition (Health ABC) study. In addition to individual lifestyle practices, a high-risk lifestyle score (0 to 4) was calculated indicating the total number of unhealthy lifestyle practices per person. Mobility limitation was defined as reported difficulty walking 1/4 mile or climbing 10 steps during two consecutive semiannual assessments over 6.5 years. Results: In non-obese older persons, significant risk factors for incident mobility limitation after adjustment for socio-demographics and health-related variables were current and former smoking [hazard ratio (HR) = 1.51; 95% confidence interval (CI), 1.20 to 1.89; HR 1.40; 95% CI, 1.12 to 1.74), former alcohol intake (HR 1.30; 95% CI, 1.05 to 1.60), low and medium physical activity (HR = 1.78; 95% CI, 1.45 to 2.18; HR = 1.29, 95% CI, 1.07 to 1.54), and eatin g an unhealthy diet (HR = 1.57; 95% CI, 1.17 to 2.10). In the obese, only low physical activity was associated with a significantly increased risk of mobility limitation (HR = 1.44; 95% CI, 1.08 to 1.92). Having two or more unhealthy lifestyle factors was a strong predictor of mobility limitation in the non-obese only (HR = 1.98; 95% CI, 1.61 to 2.43). Overall, obese persons had a significantly higher risk of mobility limitation compared with non-obese persons, independent of lifestyle factors (HR = 1.73; 95% CI, 1.52 to 1.96). Conclusions: These results underscore the importance of a healthy lifestyle for maintaining function among non-obese older adults. However, a healthy lifestyle cannot overcome the effect of obesity in obese older adults; this stresses the importance of preventing obesity to protect against mobility loss in older persons. C1 [Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Koster, Annemarie; van Gool, Coen H.; van Eijk, Jacques Th. M.; Kempen, Gertrudis I. J. M.] Univ Maastricht, Dept Hlth Care Studies, Maastricht, Netherlands. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Penninx, Brenda W. J. H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Inst Res Extramural Med Inst, Amsterdam, Netherlands. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Brach, Jennifer S.] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA USA. [Visser, Marjolein] Vrije Univ Amsterdam, Inst Hlth Sci, Fac Earth & Life Sci, Amsterdam, Netherlands. [Simonsick, Eleanor M.] Johns Hopkins Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. [Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Sect Gerontol & Geriatr Med, Winston Salem, NC 27109 USA. [Tylavsky, Frances A.] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Koster, A (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA. EM kostera@mail.nih.gov RI Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013; Kempen, Gertrudis/H-5978-2016 OI Newman, Anne/0000-0002-0106-1150; Kempen, Gertrudis/0000-0002-7053-2198 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 42 TC 41 Z9 42 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD DEC PY 2007 VL 15 IS 12 BP 3122 EP 3132 DI 10.1038/oby.2007.372 PG 11 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 254TF UT WOS:000252610200031 PM 18198323 ER PT J AU Grobman, WA Gersnoviez, R Landon, MB Spong, CY Leveno, KJ Rouse, DJ Varner, MW Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM AF Grobman, William A. Gersnoviez, Rebecca Landon, Mark B. Spong, Catherine Y. Leveno, Kenneth J. Rouse, Dwight J. Varner, Michael W. Moawad, Atef H. Caritis, Steve N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Thorp, John M. Ramin, Susan M. Mercer, Brian M. CA NICHD MFMU Network TI Pregnancy outcomes for women with placenta previa in relation to the number of prior cesarean deliveries SO OBSTETRICS AND GYNECOLOGY LA English DT Article AB OBJECTIVE: To estimate the association between the number of prior cesarean deliveries and pregnancy outcomes among women with placenta previa. METHODS: Women with a placenta previa and a singleton gestation were identified in a concurrently collected database of cesarean deliveries performed at 19 academic centers during a 4-year period. Maternal and perinatal outcomes were analyzed after stratifying by the number of cesarean deliveries before the index pregnancy. RESULTS: Of the 868 women in the analysis, 488 had no prior cesarean delivery, 252 had one prior cesarean delivery, 76 had two prior cesarean deliveries, and 52 had at least three prior cesarean deliveries. Multiple measures of maternal morbidity (eg, coagulopathy, hysterectomy, pulmonary edema) increased in frequency as the number of prior cesarean deliveries rose. Even one prior cesarean delivery was sufficient to increase the risk of an adverse maternal outcome (a composite of transfusion, hysterectomy, operative injury, coagulopathy, venous thromboembolism, pulmonary edema, or death) from 15% to 23%, which corresponded, in multivariable analysis, to an adjusted odds ratio of 1.9 (95% confidence interval 1.2-2.9). Conversely, gestational age at delivery and adverse perinatal outcome (a composite measure of respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage grade 3 or 4, seizures, or death) were unrelated to the number of prior cesarean deliveries. CONCLUSION: Among women with a placenta previa, an increasing number of prior cesarean deliveries is associated with increasing maternal, but not perinatal, morbidity. C1 Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Univ Texas San Antonio, Dept Obstet & Gynecol, San Antonio, TX USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Univ Texas Houston, Dept Obstet & Gynecol, Houston, TX USA. Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. George Washington Univ, Ctr Biostat, Dept Obstet & Gynecol, Washington, DC USA. NICHHD, Dept Obstet & Gynecol, Bethesda, MD 20892 USA. RP Grobman, WA (reprint author), 333 E Super St,Suite 410, Chicago, IL 60611 USA. EM w-grobman@northwestern.edu RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU NICHD NIH HHS [HD34208, HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34210, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560] NR 10 TC 63 Z9 72 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2007 VL 110 IS 6 BP 1249 EP 1255 DI 10.1097/01.AOG.0000292082.80566.cd PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 236LH UT WOS:000251304000007 PM 18055717 ER PT J AU Spinnato, JA Freire, S Silva, JLPE Rudge, MVC Martins-Costa, S Koch, MA Goco, N Santos, CD Cecatti, JG Costa, R Ramos, JG Moss, N Sibai, BM AF Spinnato, Joseph A., II Freire, Salvio Pinto e Silva, Joao Luiz Cunha Rudge, Marilza Vieira Martins-Costa, Sergio Koch, Matthew A. Goco, Norman Santos, Cleide de Barros Cecatti, Jose Guilherme Costa, Roberto Ramos, Jose Geraldo Moss, Nancy Sibai, Baha M. TI Antioxidant therapy to prevent preeclampsia - A Randomized controlled trial SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; VITAMIN-E; WOMEN; RISK; SUPPLEMENTATION AB OBJECTIVE: To study whether antioxidant supplementation will reduce the incidence of preeclampsia among patients at increased risk. METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted at four Brazilian sites. Women between 12 0/7 weeks and 19 6/7 weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomly assigned to daily treatment with both vitamin C (1,000 mg) and vitamin E (400 International Units) or placebo. Analyses were adjusted for clinical site and risk group (prior preeclampsia, chronic hypertension, or both). A sample size of 734 would provide 80% power to detect a 40% reduction in the risk of preeclampsia, assuming a placebo group rate of 21% and alpha=.05. The a level for the final analysis, adjusted for interim looks, was 0.0458. RESULTS: Outcome data for 707 of 739 randomly assigned patients revealed no significant reduction in the rate of preeclampsia (study drug, 13.8% [49 of 355] compared with placebo, 15.6% [55 of 352], adjusted risk ratio 0.87 [95.42% confidence interval 0.61-1.25]). There were no differences in mean gestational age at delivery or rates of perinatal mortality, abruptio placentae, pre-term delivery, and small for gestational age or low birth weight infants. Among patients without chronic hypertension, there was a slightly higher rate of severe preeclampsia in the study group (study drug, 6.5% [11 of 170] compared with placebo, 2.4% [4 of 168], exact P=.11, odds ratio 2.78, 95% confidence interval 0.79-12.62). CONCLUSION: This trial failed to demonstrate a benefit of antioxidant supplementation in reducing the rate of preeclampsia among'patients with chronic hypertension and/or prior preeclampsia. C1 Univ Cincinnati, Coll Med, Dept Obstet & Gynecol, Cincinnati, OH USA. Univ Fed Pernambuco, Hosp Clin, Recife, PE, Brazil. Univ Estadual Campinas, Campinas, Brazil. Univ Estadual Paulista, Botucatu, SP, Brazil. Univ Fed Rio Grande do Sul, Hosp Clin, Porto Alegre, RS, Brazil. RTI Int, Res Triangle Pk, NC USA. NICHHD, Bethesda, MD 20892 USA. RP Spinnato, JA (reprint author), Univ Cincinnati, Coll Med, Dept Obstet & Gynecol, POB 2670526, Cincinnati, OH USA. EM spinnaja@ucmail.uc.edu RI Rudge, Marilza /C-8338-2012 OI Rudge, Marilza /0000-0002-9227-832X FU NICHD NIH HHS [1 U01 HD40565] NR 12 TC 80 Z9 85 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2007 VL 110 IS 6 BP 1311 EP 1318 DI 10.1097/01.AOG.0000289576.43441.1f PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 236LH UT WOS:000251304000016 PM 18055726 ER PT J AU Zhu, JL Obel, C Bech, BH Olsen, J Basso, O AF Zhu, Jin Liang Obel, Carsten Bech, Bodil Hammer Olsen, Jorn Basso, Olga TI Infertility, infertility treatment, and fetal growth restriction SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID NATIONAL BIRTH COHORT; IN-VITRO FERTILIZATION; PRETERM DELIVERY; PREGNANCY; WEIGHT; RISK; TIME; IVF; SUBFERTILITY; CONCEPTION AB OBJECTIVE: To examine the association between infertility, with or without treatment, and fetal growth, as well as perinatal and infant mortality. METHODS: From the Danish National Birth Cohort (1997-2003), we identified 51,041 singletons born of fertile couples (time to pregnancy 12 months or less) 5,787 born of infertile couples conceiving naturally (time to pregnancy more than 12 months), and 4,317 born after treatment. We defined small for gestational age (SGA) as the lowest 5% of birth weight by sex and gestational age. RESULTS: Crude estimates suggested an increased risk of perinatal mortality and SGA among infertile couples (treated and untreated), but the odds ratios (ORs) of perinatal mortality among infertile couples were attenuated after adjustment for maternal age and body mass index (1.32, 95% confidence interval [Cl] 0.95-1.84 among untreated and 1.26, 95% Cl 0.86-1.85 among treated couples). The elevated risk of SGA among infertile couples persisted after adjustment for maternal age, parity, and smoking (OR 1.24, 95% Cl 1.10-1.40 among untreated, and OR 1.40, 95% Cl 1.23-1.60 among treated). The risk of SGA increased with time to pregnancy, and a longer time to pregnancy was associated with a small reduction in birth weight across the whole distribution. CONCLUSION: The increased risk of SGA observed among infertile couples with or without infertility treatment suggests that infertility may be a risk factor for intrauterine growth restriction. Treatment per se may have little effect on fetal growth. A small-to-moderate increased risk of perinatal mortality in infertile couples cannot be ruled out due to the small number of cases. C1 Univ Aarhus, Danish Epidemiol Sci Ctr, Dept Epidemiol, Inst Publ Hlth, DK-8000 Aarhus C, Denmark. Aarhus Univ Hosp, Dept Gynaecol & Obstet, Perinatal Epidemiol Res Unit, DK-8000 Aarhus N, Denmark. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC USA. RP Zhu, JL (reprint author), Univ Aarhus, Danish Epidemiol Sci Ctr, Dept Epidemiol, Inst Publ Hlth, Vennelyst Blvd 6, DK-8000 Aarhus C, Denmark. EM zjl@soci.au.dk RI Basso, Olga/E-5384-2010; Olsen, Jorn/F-8801-2015; Bech, Bodil Hammer/B-9646-2016 OI Basso, Olga/0000-0001-9298-4921; Olsen, Jorn/0000-0001-7462-5140; FU Intramural NIH HHS [Z99 ES999999] NR 28 TC 32 Z9 32 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2007 VL 110 IS 6 BP 1326 EP 1334 DI 10.1097/01.AOG.0000290330.80256.97 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 236LH UT WOS:000251304000018 PM 18055728 ER PT J AU Spong, CY AF Spong, Catherine Y. TI Prediction and prevention of recurrent spontaneous preterm birth - Reply SO OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. RP Spong, CY (reprint author), NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2007 VL 110 IS 6 BP 1425 EP 1425 DI 10.1097/01.AOG.0000296100.06542.de PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 236LH UT WOS:000251304000037 ER PT J AU Safaeian, M Solomon, D Castle, PE AF Safaeian, Mahboobeh Solomon, Diane Castle, Philip E. TI Cervical cancer prevention - Cervical screening: Science in evolution SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID HUMAN-PAPILLOMAVIRUS DNA; ATYPICAL SQUAMOUS-CELLS; RANDOMIZED CONTROLLED-TRIAL; CYTOLOGICALLY NORMAL WOMEN; ASCUS-LSIL TRIAGE; FOLLOW-UP; UNITED-STATES; INTRAEPITHELIAL NEOPLASIA; COST-EFFECTIVENESS; UNDETERMINED SIGNIFICANCE AB The incidence and mortality of cervical cancer in the United States has declined by more than 70% since the 1950s. This decline is attributed mainly to the introduction of Papanicolaou's test in the 1940s. Cervical cancer, however, remains the second most frequent of all female malignancies worldwide, with 80% of the cases occurring in resource-poor countries. This disparity is attributed primarily to the lack of screening and treatment of precancerous lesions. This article describes the traditional methods of screening for cervical cancer and innovative methods that might help overcome financial and cultural barriers to more widespread screening. C1 [Safaeian, Mahboobeh; Castle, Philip E.] Natl Canc Inst, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,Natl Inst Hlth, Rockville, MD 20852 USA. [Solomon, Diane] Natl Canc Inst, Div Canc Prevent, Dept Hlth & Human Serv, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Safaeian, M (reprint author), Natl Canc Inst, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,Natl Inst Hlth, 6120 Execut Blvd,EPS,Suite 550, Rockville, MD 20852 USA. EM safacianm@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 82 TC 30 Z9 32 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 0889-8545 J9 OBSTET GYN CLIN N AM JI Obstet. Gynecol. Clin. N. Am. PD DEC PY 2007 VL 34 IS 4 BP 739 EP + DI 10.1016/j.ogc.2007.09.004 PG 23 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 250IW UT WOS:000252294300009 PM 18061867 ER PT J AU Boyiadzis, M Pavletic, S Foon, KA AF Boyiadzis, Michael Pavletic, Steven Foon, Kenneth A. TI New therapeutic options for chronic lymphocytic leukemia - The Lin article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 [Boyiadzis, Michael; Foon, Kenneth A.] Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol,Canc Inst, Pittsburgh, PA 15260 USA. [Pavletic, Steven] NCI, Natl Inst Hlth, Graft Versus Host & Autoimmunity Unit, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Boyiadzis, M (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol,Canc Inst, Pittsburgh, PA 15260 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2007 VL 21 IS 14 BP 1649 EP + PG 2 WC Oncology SC Oncology GA 270RX UT WOS:000253739000002 ER PT J AU Newlands, SD Sklare, DA AF Newlands, Shawn D. Sklare, Daniel A. TI Developing the next generation of otolaryngologist-researchers SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID CLINICIAN-SCIENTIST AB The lifeblood of any specialty is innovation and discovery. It is important for the field of otolaryngology and its patients that we identify, recruit, train, and develop the next generation of researchers in otolaryngology. This article describes programs and resources currently available to otolaryngologists in training and early in their career for their development as clinician-scientists. We describe the background of the current generation of National Institutes of Health-funded otolaryngologists; and discern where the next generation might come from. Special attention is given to the National Institute on Deafness and Other Communication Disorders, which focuses on supporting research and research training in hearing, balance, smell, taste, voice, speech, and language, and to programs aimed at the development of clinician-scientists. C1 [Newlands, Shawn D.] Univ Texas Med Branch, Dept Otolaryngol, Galveston, TX 77555 USA. [Sklare, Daniel A.] Natl Inst Deafness & Other Commun Disorders, NIH, Div Sci Programs, Rockville, MD 20892 USA. RP Newlands, SD (reprint author), Univ Texas Med Branch, Dept Otolaryngol, 301 Univ Blvd, Galveston, TX 77555 USA. EM sdnewlan@utmb.edu NR 14 TC 3 Z9 3 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 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD DEC PY 2007 VL 40 IS 6 BP 1295 EP + DI 10.1016/j.otc.2007.07.008 PG 16 WC Otorhinolaryngology SC Otorhinolaryngology GA 243FE UT WOS:000251779800010 PM 18021841 ER PT J AU Kim, HJ Lonser, RR AF Kim, H. Jeffrey Lonser, Russell R. TI Cochlear implantation for hearing loss associated with bilateral endolymphatic sac tumors in Von Hippel-Lindau disease - In reply SO OTOLOGY & NEUROTOLOGY LA English DT Letter C1 NINDS, NIH, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Kim, HJ (reprint author), NINDS, NIH, Surg Neurol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. 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 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD DEC PY 2007 VL 28 IS 8 BP 1161 EP 1161 PG 1 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 237FF UT WOS:000251358900034 ER PT J AU Zou, J Nagy, G AF Zou, Jie Nagy, George TI Visible models for interactive pattern recognition SO PATTERN RECOGNITION LETTERS LA English DT Article DE pattern recognition; human-computer interaction; visible model; face recognition; flower recognition ID FACE-RECOGNITION; IMAGE RETRIEVAL; SEGMENTATION; CLASSIFIER; ALGORITHMS AB The exchange of information between human and machine has been a bottleneck in interactive visual classification. The visible model of an object to be recognized is an abstraction of the object superimposed on its picture. It is constructed by the machine but it can be modified by the operator. The model guides the extraction of features from the picture. The classes are rank ordered according to the similarities (in the hidden high-dimensional feature space) between the unknown picture and a set of labeled reference pictures. The operator can either accept one of the top three candidates by clicking on a displayed reference picture, or modify the model. Model adjustment results in the extraction of new features, and a new rank ordering. The model and feature extraction parameters are re-estimated after each classified object, with its model and label, is added to the reference database. Pilot experiments show that interactive recognition of flowers and faces is more accurate than automated classification, faster than unaided human classification, and that both machine and human performance improve with use. (c) 2007 Elsevier B.V. All rights reserved. C1 Rensselaer Polytech Inst, Dept Elect Comp & Syst Engn, DocLab, Troy, NY 12180 USA. Natl Lib Med, Bethesda, MD 20894 USA. RP Nagy, G (reprint author), Rensselaer Polytech Inst, Dept Elect Comp & Syst Engn, DocLab, JEC 6020,110 8th St, Troy, NY 12180 USA. EM jzou@mail.nlm.nih.gov; nagy@ecse.rpi.edu NR 43 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8655 EI 1872-7344 J9 PATTERN RECOGN LETT JI Pattern Recognit. Lett. PD DEC 1 PY 2007 VL 28 IS 16 BP 2335 EP 2342 DI 10.1016/j.patrec.2007.08.005 PG 8 WC Computer Science, Artificial Intelligence SC Computer Science GA 230TW UT WOS:000250899800017 ER PT J AU Houghton, PJ Morton, CL Tucker, C Payne, D Favours, E Cole, C Gorlick, R Kolb, EA Zhang, W Lock, R Carol, H Tajbakhsh, M Reynolds, CP Maris, JM Courtright, J Keir, ST Friedman, HS Stopford, C Zeidner, J Wu, J Liu, T Billups, CA Khan, J Ansher, S Zhang, J Smith, MA AF Houghton, Peter J. Morton, Christopher L. Tucker, Chandra Payne, Debbie Favours, Edward Cole, Claire Gorlick, Richard Kolb, E. Anders Zhang, Wendong Lock, Richard Carol, Hernan Tajbakhsh, Mimi Reynolds, C. Patrick Maris, John M. Courtright, Joshua Keir, Stephen T. Friedman, Henry S. Stopford, Charles Zeidner, Joseph Wu, Jianrong Liu, Tiebin Billups, Catherine A. Khan, Javed Ansher, Sherry Zhang, Jian Smith, Malcolm A. TI The pediatric preclinical testing program: Description of models and early testing results SO PEDIATRIC BLOOD & CANCER LA English DT Article DE cyclophosphamide; developmental therapeutics; preclinical testing; vincristine ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MALIGNANT SOLID TUMORS; HIGH-DOSE IFOSFAMIDE; CANCER MODELS; IN-VIVO; PHASE-II; NEUROBLASTOMA XENOGRAFTS; METASTATIC NEUROBLASTOMA; VINCRISTINE NSC-67574; RISK NEUROBLASTOMA AB Background. The Pediatric Preclinical Testing Program (PPTP) is an initiative supported by the National Cancer Institute (NCI) to identify novel therapeutic agents that may have significant activity against childhood cancers. The PPTP has established panels of childhood cancer xenografts and cell lines to be used for in vivo and in vitro testing. These include panels for Wilms tumor, sarcomas (rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), neuroblastoma, brain tumors (glioblastoma, ependymoma, and medulloblastoma), rhabdoid tumors (CNS and renal), and acute lymphoblastic leukemia (ALL). Here, we describe the characteristics of the in vivo tumor panels and report results for the in vivo evaluation of two standard agents, vincristine and cyclophosphamide.. Procedures. Solid tumors were grown subcutaneously in immune-deficient mice and tumor dimensions were measured weekly. ALL xenografts were inoculated intravenously and human CD45-positive cells were enumerated weekly. Results. Vincristine-induced objective responses in 6 of 24 (25%0) and cyclophosphamide-induced objective responses in 18 of 28 (64%) solid tumor models. Comparable assessments of high levels of activity for these two agents were obtained using a tumor growth delay (TGD) measure. Both agents induced regressions in each of the ALL models evaluated. Conclusions. We have established 51 solid tumor and 10 ALL in vivo models. The models identify vincristine and cyclophosphamide as having broad-spectrum activity. The PPTP tumor panels appear to generally recapitulate the activity of these agents against specific childhood cancers and to have the potential for identifying novel agents having significant clinical activity. C1 St Jude Childrens Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. Childrens Hosp Montefiore, Bronx, NY USA. Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Penn, Sch Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Abraham Family Canc Res Inst, Philadelphia, PA USA. NCI, Pediat Oncol Branch, Oncogen Sect, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Houghton, PJ (reprint author), St Jude Childrens Hosp, Dept Mol Pharmacol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM peter.houghton@stjude.org RI leng, xianwei/F-9073-2011; Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Khan, Javed/P-9157-2014; Lock, Richard/G-4253-2013; OI Carol, Hernan/0000-0002-9443-8032; Khan, Javed/0000-0002-5858-0488; Reynolds, C. Patrick/0000-0002-2827-8536 FU NCI NIH HHS [N01-CM-42216] NR 39 TC 234 Z9 237 U1 0 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2007 VL 49 IS 7 BP 928 EP 940 DI 10.1002/pbc.21078 PG 13 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 224ZV UT WOS:000250487800011 PM 17066459 ER PT J AU Bennett, PH AF Bennett, Peter H. TI An internist's perspective: Type 2 diabetes in childhood and adolescence: what does the future hold? SO PEDIATRIC DIABETES LA English DT Editorial Material ID PIMA-INDIANS; YOUTH; COMPLICATIONS; NEPHROPATHY; PREVALENCE; MELLITUS; CHILDREN; YOUNG C1 NIDDK, Phoenix, AZ 85014 USA. RP Bennett, PH (reprint author), NIDDK, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM pbennett@nih.gov NR 12 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD DEC PY 2007 VL 8 IS 6 BP 352 EP 353 DI 10.1111/j.1399-5448.2007.00354.x PG 2 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 254GI UT WOS:000252574000002 PM 18036059 ER PT J AU Emerson, SU Purcell, RH AF Emerson, Suzanne U. Purcell, Robert H. TI Hepatitis E SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Editorial Material DE hepatitis; hepatitis E ID E-VIRUS; PREVALENCE; ANTIBODIES C1 NIAID, Infect Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Emerson, SU (reprint author), NIAID, Infect Dis Lab, Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD DEC PY 2007 VL 26 IS 12 BP 1147 EP 1148 DI 10.1097/INF.0b013e31815dd7c2 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 238IF UT WOS:000251440100013 PM 18043454 ER PT J AU Blake, SM Kiely, M Gard, CC El-Mohandes, AAE El-Khorazaty, MN AF Blake, Susan M. Kiely, Michele Gard, Charlotte C. El-Mohandes, Ayman A. E. El-Khorazaty, M. Nabil CA NIH-DC Initiative TI Pregnancy intentions and happiness among pregnant black women at high risk for adverse infant health outcomes SO PERSPECTIVES ON SEXUAL AND REPRODUCTIVE HEALTH LA English DT Article ID ANTENATAL PSYCHOSOCIAL HEALTH; MOOD REGULATION EXPECTANCIES; RANDOMIZED CONTROLLED-TRIAL; UNINTENDED PREGNANCY; PRENATAL-CARE; UNWANTED PREGNANCIES; NATIONAL-SURVEY; FAMILY GROWTH; UNITED-STATES; ALPHA-FORM AB CONTEXT: Unintended pregnancy is associated with risk behaviors and increased morbidity or mortality for mothers and infants, but a woman's feelings about pregnancy may be more predictive of risk and health outcomes than her intentions. METHODS: A sample of 1,044 black women who were at increased risk were enrolled at prenatal care clinics in the District of Columbia in 2001-2003. Bivariate and multivariate analyses assessed associations between pregnancy intentions or level of happiness about being pregnant and multiple psychosocial and behavioral risk factors, and identified correlates of happiness to be pregnant. RESULTS. Pregnancy intentions and happiness were strongly associated, but happiness was the better predictor of risk. Unhappy women had higher odds than happy women of smoking, being depressed, experiencing intimate partner violence, drinking and using illicit drugs (odds ratios, 1.7-2.6). The odds of being happy were reduced among women who had other children or a child younger than two, who were single or did not have a current partner, who had had more than one sexual partner in the past year and who reported that the baby's father did not want the pregnancy (0.3-0.6). In contrast, the odds of being happy were elevated among women who had better coping strategies (1.03), who had not used birth control at conception (1.6) and who had 1-2 household members, rather than five or more (2.1). CONCLUSIONS: Additional psychosocial screening for happiness about being pregnant and for partner characteristics, particularly the father's desire to have this child, may help improve prenatal care services and prevent adverse health outcomes. C1 George Washington Univ, Med Ctr, Dept Prevent & Community Hlth, Washington, DC 20037 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Collaborat Studies Unit, Rockville, MD USA. RTI Int, Rockville, MD USA. RP Blake, SM (reprint author), George Washington Univ, Med Ctr, Dept Prevent & Community Hlth, Washington, DC 20037 USA. EM Smblake@gwu.edu FU NICHD NIH HHS [5U18HD036104, U01HD31206] NR 72 TC 22 Z9 23 U1 2 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-6341 J9 PERSPECT SEX REPRO H JI Perspect. Sex Reprod. Health PD DEC PY 2007 VL 39 IS 4 BP 194 EP 205 DI 10.1363/3919407 PG 12 WC Demography; Family Studies SC Demography; Family Studies GA 239GI UT WOS:000251506400001 PM 18093036 ER PT J AU Dietrich, A Kalwa, H Storch, U Schnitzler, MMY Salanova, B Pinkenburg, O Dubrovska, G Essin, K Gollasch, M Birnbaumer, L Gudermann, T AF Dietrich, Alexander Kalwa, Hermann Storch, Ursula Mederos y Schnitzler, Michael Salanova, Birgit Pinkenburg, Olaf Dubrovska, Galyna Essin, Kirill Gollasch, Maik Birnbaumer, Lutz Gudermann, Thomas TI Pressure-induced and store-operated cation influx in vascular smooth muscle cells is independent of TRPC1 SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE TRPC1-deficient mice; classical transient receptor channel 1; store-operated cation influx; pressure-induced cation influx; Bayliss effect; STIM1; thapsigargin; inositol-1,4,5 trisphosphate ID RECEPTOR POTENTIAL CHANNELS; CALCIUM-CHANNEL; PLASMA-MEMBRANE; DROSOPHILA TRP; HUMAN HOMOLOG; CRAC CHANNEL; CA2+ SENSOR; SUBUNIT; STIM1; CONTRACTILITY AB Among the classical transient receptor potential (TRPC) subfamily, TRPC1 is described as a mechanosensitive and store-operated channel proposed to be activated by hypoosmotic cell swelling and positive pipette pressure as well as regulated by the filling status of intracellular Ca2+ stores. However, evidence for a physiological role of TRPC1 may most compellingly be obtained by the analysis of a TRPC1-deficient mouse model. Therefore, we have developed and analyzed TRPC1(-/-) mice. Pressure-induced constriction of cerebral arteries was not impaired in TRPC1(-/-) mice. Smooth muscle cells from cerebral arteries activated by hypoosmotic swelling and positive pipette pressure showed no significant differences in cation currents compared to wild-type cells. Moreover, smooth muscle cells of TRPC1(-/-) mice isolated from thoracic aortas and cerebral arteries showed no change in store-operated cation influx induced by thapsigargin, inositol-1,4,5 trisphosphate, and cyclopiazonic acid compared to cells from wild-type mice. In contrast to these results, small interference RNAs decreasing the expression of stromal interaction molecule 1 (STIM1) inhibited thapsigargin-induced store-operated cation influx, demonstrating that STIM1 and TRPC1 are mutually independent. These findings also imply that, as opposed to current concepts, TRPC1 is not an obligatory component of store-operated and stretch-activated ion channel complexes in vascular smooth muscle cells. C1 Univ Marburg, Inst Pharmakol & Toxikol, D-35043 Marburg, Germany. Max Delbruck Ctr, Charite, Fac Med, Helios Klinikum Berlin,Franz Volhard Klin,MKSNII, Berlin, Germany. NIEHS, Res Triangle Pk, NC 27709 USA. RP Dietrich, A (reprint author), Univ Marburg, Inst Pharmakol & Toxikol, Karl-von-Frisch-Str 1, D-35043 Marburg, Germany. EM dietrica@staff.uni-marburg.de RI Dietrich, Alexander/G-8619-2013; OI Dietrich, Alexander/0000-0002-1168-8707 NR 34 TC 148 Z9 151 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD DEC PY 2007 VL 455 IS 3 BP 465 EP 477 DI 10.1007/s00424-007-0314-3 PG 13 WC Physiology SC Physiology GA 223OO UT WOS:000250380800006 PM 17647013 ER PT J AU Xu, K Anderson, TR Neyer, KM Lamparella, N Jenkins, G Zhou, Z Yuan, Q Virkkunen, M Lipsky, RH AF Xu, K. Anderson, T. R. Neyer, K. M. Lamparella, N. Jenkins, G. Zhou, Z. Yuan, Q. Virkkunen, M. Lipsky, R. H. TI Nucleotide sequence variation within the human tyrosine kinase B neurotrophin receptor gene: association with antisocial alcohol dependence SO PHARMACOGENOMICS JOURNAL LA English DT Article DE alcoholism; TrkB; NTRK2 gene; single nucleotide polymorphism; association; haplotype ID HAPLOTYPE BLOCKS; RAT HIPPOCAMPUS; HUMAN GENOME; VULNERABILITY; CONSUMPTION; ADDICTION; LINKAGE; LOCI; SUSCEPTIBILITY; POLYMORPHISM AB To identify sequence variants in genes that may have roles in neuronal responses to alcohol, we resequenced the 5' region of tyrosine kinase B neurotrophin receptor gene (NTRK2) and determined linkage disequilibrium (LD) values, haplotype structure, and performed association analyses using 43 single nucleotide polymorphisms (SNPs) covering the entire NTRK2 region in a Finnish Caucasian sample of 229 alcohol-dependent subjects with antisocial personality disorder (ASPD) and 287 healthy controls. Individually, three SNPs were associated with alcohol dependence and alcohol abuse (AD) (P-value from 0.0019 to 0.0059, significance level was set at P <= 0.01 corrected for multiple testing), whereas a common 18 locus haplotype within the largest LD block of NTRK2, a 119-kb region containing the 5' flanking region and exons 1-15, was marginally overrepresented in control subjects compared to AD individuals (global P=0.057). Taken together, these results support a role for the NTRK2 gene in addiction in a Caucasian population with AD and a subtype of ASPD. C1 Natl Inst Hlth, NIAAA, Neurogenet Lab, Sect Mol Genet & Human Genet, Bethesda, MD USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. RP Lipsky, RH (reprint author), Natl Inst Hlth, NIAAA, Neurogenet Lab, Mol Genet Sect, 5625 Fishers Lane,Rm 3S32, Rockville, MD 20852 USA. EM rlipsky@mail.nih.gov OI Lipsky, Robert/0000-0001-7753-1473 FU Intramural NIH HHS [Z99 AA999999, Z01 AA000326-02]; NIAAA NIH HHS [Z01 AA000325] NR 37 TC 18 Z9 19 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD DEC PY 2007 VL 7 IS 6 BP 368 EP 379 DI 10.1038/sj.tpj.6500430 PG 12 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 234OI UT WOS:000251173000001 PM 17200667 ER PT J AU Casad, V Cortes, A Ciruela, F Mallol, J Ferre, S Lluis, C Canela, EI Franco, R AF Casad, Vincent Cortes, Antoni Ciruela, Francisco Mallol, Josefa Ferre, Sergi Lluis, Carmen Canela, Enric I. Franco, Rafael TI Old and new ways to calculate the affinity of agonists and antagonists interacting with G-protein-coupled monomeric and dimeric receptors: The receptor-dimer cooperativity index SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE affinity; agonist; antagonist; G protein ID CARDIAC MUSCARINIC RECEPTORS; A(1) ADENOSINE RECEPTORS; TERNARY COMPLEX MODEL; PIG CEREBRAL-CORTEX; LINKED RECEPTORS; OCCUPANCY MODEL; BETA(2)-ADRENERGIC RECEPTOR; ACETYLCHOLINE-RECEPTORS; NEGATIVE COOPERATIVITY; CONSTITUTIVE ACTIVITY AB Almost all existing models that explain heptahelical G-protein-coupled receptor (GPCR) operation are based on the occurrence of monomeric receptor species. However, an increasing number of studies show that many G-protein-coupled heptahelical membrane receptors (HMR) are expressed in the plasma membrane as dimers. We here review the approaches for fitting ligand binding data that are based on the existence of receptor monomers and also the new ones based on the existence of receptor dimers. The reasons for equivocal interpretations of the fitting of data to receptor dimers, assuming they are monomers, are also discussed. A recently devised model for receptor dimers provides a new approach for fitting data that eventually gives more accurate and physiological relevant parameters. Fitting data using the new procedure gives not only the equilibrium dissociation constants for high- and low-affinity binding to receptor dimers but also a "cooperativity index" that reflects the molecular communication within the dimer. A comprehensive way to fit binding data from saturation isotherms and from competition assays to a dimer receptor model is reported and compared with the traditional way of fitting data. The new procedure can be applied to any receptor forming dimers; from receptor tyrosine kinases to intracellular receptors (e.g., estrogen receptor) and in general for ligand binding to proteins forming dimers. (C) 2007 Published by Elsevier Inc. C1 [Casad, Vincent; Cortes, Antoni; Ciruela, Francisco; Mallol, Josefa; Lluis, Carmen; Canela, Enric I.; Franco, Rafael] Univ Barcelona, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain. [Casad, Vincent; Cortes, Antoni; Ciruela, Francisco; Mallol, Josefa; Lluis, Carmen; Canela, Enric I.; Franco, Rafael] CIBERNED, IDIBAPS, Spain Inst Invest Biomed August Pi Sunyer, Barcelona, Spain. [Ferre, Sergi] NIDA, IRP, NIH, DHHS, Baltimore, MD 21224 USA. RP Franco, R (reprint author), Univ Barcelona, Dept Bioquim & Biol Mol, Av Diagonal, 645, E-08028 Barcelona, Spain. EM rftanco@ub.edu RI Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014; OI Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Casado, Vicent/0000-0002-1764-3825 FU Intramural NIH HHS NR 58 TC 38 Z9 39 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD DEC PY 2007 VL 116 IS 3 BP 343 EP 354 DI 10.1016/j.pharmthera.2007.05.010 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 243QI UT WOS:000251812000001 PM 17935788 ER PT J AU Shi, YB Fu, L Hasebe, T Ishizuya-Oka, A AF Shi, Yun-Bo Fu, Liezhen Hasebe, Takashi Ishizuya-Oka, Atsuko TI Regulation of extracellular matrix remodeling and cell fate determination by matrix metalloproteinase stromelysin-3 during thyroid hormone-dependent post-embryonic development SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE thyroid hormone receptor; extracellular matrix; matrix metalloproteinase; Xenopus laevis; metamorphosis; apoptosis ID LAMININ-BINDING PROTEIN; XENOPUS-LAEVIS METAMORPHOSIS; GENE-EXPRESSION; AMPHIBIAN METAMORPHOSIS; INTESTINAL EPITHELIUM; FROG METAMORPHOSIS; BREAST-CARCINOMA; MESSENGER-RNA; IN-VIVO; TRANSCRIPTIONAL REGULATION AB Interactions between cells and extracellular matrix (ECM), in particular the basement membrane (BM), are fundamentally important for the regulation of a wide variety of physiological and pathological processes. Matrix metalloproteinases (MMP) play critical roles in ECM remodeling and/or regulation of cell-ECM interactions because of their ability to cleave protein components of the ECM. Of particular interest among MMP is stromelysin-3 (ST3), which was first isolated from a human breast cancer and also shown to be correlated with apoptosis during development and invasion of tumor cells in mammals. We have been using intestinal remodeling during thyroid hormone (TH)-dependent amphibian metamorphosis as a model to study the role of ST3 during post-embryonic tissue remodeling and organ development in vertebrates. This process involves complete degeneration of the tadpole or larval epithelium through apoptosis and de novo development of the adult epithelium. Here, we will first summarize expression studies by us and others showing a tight spatial and temporal correlation of the expression of ST3 mRNA and protein with larval cell death and adult tissue development. We will then review in vitro and in vivo data supporting a critical role of ST3 in TH-induced larval epithelial cell death and ECM remodeling. We will further discuss the potential mechanisms of ST3 function during metamorphosis and its broader implications. (C) 2007 Elsevier Inc. All rights reserved. C1 [Shi, Yun-Bo; Fu, Liezhen] NIH, NICHHD, Lab Gene Regulat & Devt, Bethesda, MD 20892 USA. [Hasebe, Takashi; Ishizuya-Oka, Atsuko] Nippon Med Coll, Dept Biol, Nakahara Ku, Kanagawa 2110063, Japan. RP Shi, YB (reprint author), NIH, NICHHD, Lab Gene Regulat & Devt, Bldg 18T, Rm 106, Bethesda, MD 20892 USA. EM shi@helix.nih.gov; a-oka@nms.ae.jp FU Intramural NIH HHS [Z01 HD001901-12] NR 104 TC 20 Z9 21 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD DEC PY 2007 VL 116 IS 3 BP 391 EP 400 DI 10.1016/j.pharmthera.2007.07.005 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 243QI UT WOS:000251812000003 PM 17919732 ER PT J AU Bansal, G Druey, KM Xie, Z AF Bansal, Geetanjall Druey, Kirk M. Xie, Zhihui TI R4 RGS proteins: Regulation of G-protein signaling and beyond SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE G proteins; signal transduction; RGS proteins ID GTPASE-ACTIVATING PROTEINS; SMOOTH-MUSCLE-CELLS; HETEROTRIMERIC G-PROTEINS; MESSENGER-RNA EXPRESSION; BETA-GAMMA-SUBUNITS; N-TERMINAL DOMAIN; AUTONOMIC NERVOUS-SYSTEM; RECTIFYING K+ CHANNEL; G-ALPHA-Q; COUPLED-RECEPTORS AB The regulators of G-protein signaling (RGS) proteins were initially characterized as inhibitors of signal transduction cascades initiated by G-protein-coupled receptors (GPCR) because of their ability to increase the intrinsic GTPase activity of heterotrimeric G proteins. This GTPase accelerating protein (GAP) activity enhances G protein deactivation and promotes desensitization. However, in addition to this signature trait, emerging data have revealed an expanding network of proteins, lipids, and ions that interact with RGS proteins and confer additional regulatory functions. This review highlights recent advances in our understanding of the physiological functions of one subfamily of RGS proteins with a high degree of homology (B/R4) gleaned from recent studies of knockout mice or cells with reduced RGS expression. We also discuss some of the newly appreciated interactions of RGS proteins with cellular factors that suggest RGS control of several components of G-protein-mediated pathways, as well as a diverse array of non-GPCR-mediated biological responses. Published by Elsevier Inc. C1 [Bansal, Geetanjall; Druey, Kirk M.; Xie, Zhihui] NIH, NIAID, Lab Allerg Dis, Mol Signal Transduct Sect, Bethesda, MD 20892 USA. RP Druey, KM (reprint author), NIH, NIAID, Lab Allerg Dis, 9000 Rockville Pike, 10 Ctr Dr, Rm 11N242, Bethesda, MD 20892 USA. EM KDRUEY@niaid.nih.gov RI Bansal, Geetanjali/C-3854-2009 FU Intramural NIH HHS [Z01 AI000746-10, Z99 AI999999] NR 204 TC 107 Z9 114 U1 4 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD DEC PY 2007 VL 116 IS 3 BP 473 EP 495 DI 10.1016/j.pharmthera.2007.09.005 PG 23 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 243QI UT WOS:000251812000009 PM 18006065 ER PT J AU Mertz, EL AF Mertz, Edward L. TI Conditions for insensitivity of the microscopic-scale dielectric response to structural details of dipolar liquids SO PHYSICAL REVIEW E LA English DT Article ID DENSITY-FUNCTIONAL THEORY; COMPUTER-SIMULATION; MOLECULAR LIQUIDS; ELECTRON-TRANSFER; SOLVENT MODELS; WATER; FORMULATION; SOLVATION; FREQUENCY; RELAXATION AB Details of condensed matter structure can alter microscopic-scale response to electric fields by orders of magnitude. It is shown that dipolar liquids near boundaries is an exception where the response can be virtually insensitive to such details and can sense mainly the macroscopic dielectric permittivity. This insensitivity is due to fluidity, symmetry properties, and location of the fields' charges outside the liquid or inside impermeable solute cavities, which is the ubiquitous location in molecular scale phenomena. C1 NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Mertz, EL (reprint author), NICHHD, NIH, Dept Hlth & Human Serv, 9000 Rockville Pike,Bldg 9,Room 1E125, Bethesda, MD 20892 USA. EM mertze@mail.nih.gov NR 36 TC 1 Z9 1 U1 0 U2 4 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD DEC PY 2007 VL 76 IS 6 AR 062503 DI 10.1103/PhysRevE.76.062503 PN 1 PG 4 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 246CR UT WOS:000251985600084 PM 18233884 ER PT J AU Maring, JR Croarkin, E AF Maring, Joyce R. Croarkin, Earllaine TI Presentation and progression of Friedreich ataxia and implications for physical therapist examination SO PHYSICAL THERAPY LA English DT Article ID SPINAL MUSCULAR-ATROPHY; RATING-SCALE ICARS; NATURAL-HISTORY; INTERRATER RELIABILITY; PERFORMANCE-MEASURES; MULTIPLE-SCLEROSIS; REPEAT EXPANSION; DISEASE; SCOLIOSIS; EXERCISE AB Friedreich ataxia, although rare, is the most prevalent inherited ataxia. Recent insight into them disease pathogenesis is creating new hope for effective therapies. The purposes of this update are: (1) to review the etiology, presentation, and progression of Friedreich ataxia and (2) to describe a comprehensive physical therapist, examination emphasizing valid and reliable performance measurements associated with disease progression. Early identification of individuals with Friedreich ataxia and precise characterization of impairments and functional limitations gain importance as new drug therapies are considered. C1 [Maring, Joyce R.] George Washington Univ, Program Phys Therapy, Washington, DC 20037 USA. [Croarkin, Earllaine] Natl Inst Neurol Disorders & Stroke, Dept Rehabil Med, NIH, Bethesda, MD USA. RP Maring, JR (reprint author), George Washington Univ, Program Phys Therapy, 900 23rd St NW,6140, Washington, DC 20037 USA. EM hspjxm@gwumc.edu NR 71 TC 12 Z9 12 U1 0 U2 3 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD DEC PY 2007 VL 87 IS 12 BP 1687 EP 1696 DI 10.2522/ptj.20060232 PG 10 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 240EX UT WOS:000251571100015 PM 17911272 ER PT J AU Pisitkun, T Hoffert, JD Yu, MJ Knepper, MA AF Pisitkun, Trairak Hoffert, Jason D. Yu, Ming-Jiun Knepper, Mark A. TI Tandem mass spectrometry in physiology SO PHYSIOLOGY LA English DT Review ID MEDULLARY COLLECTING DUCT; PROTEOMIC ANALYSIS; SACCHAROMYCES-CEREVISIAE; PROTEIN IDENTIFICATION; LC-MS/MS; AQUAPORIN-2; VASOPRESSIN; CELLS; PHOSPHORYLATION; RAT AB Tandem mass spectrometry coupled to liquid chromatography (LC-MS/MS) allows identification of proteins in a complex mixture without need for protein purification ("shotgun" proteomics). Recent progress in LC-MS/MS-based quantification, phosphoproteomic analysis, and targeted LC-MS/MS using multiple reaction monitoring (MRM) has made LC-MS/MS a powerful tool for the study of cell physiology. C1 [Pisitkun, Trairak; Hoffert, Jason D.; Yu, Ming-Jiun; Knepper, Mark A.] NHLBI, Natl Inst Hlth, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Pisitkun, T (reprint author), NHLBI, Natl Inst Hlth, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. EM knep@helix.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271; YU, MING-JIUN/0000-0003-0393-4696 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [HL-001285] NR 37 TC 12 Z9 13 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1548-9213 J9 PHYSIOLOGY JI Physiology PD DEC PY 2007 VL 22 IS 6 BP 390 EP 400 DI 10.1152/physiol.00025.2007 PG 11 WC Physiology SC Physiology GA 240BP UT WOS:000251562300006 PM 18073412 ER PT J AU Brinton, LA AF Brinton, Louise A. TI The relationship of silicone breast implants and cancer at other sites SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID AUGMENTATION MAMMAPLASTY PATIENTS; GENETICALLY SUSCEPTIBLE STRAINS; T-CELL LYMPHOMA; MONOCLONAL GAMMOPATHY; MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE; SWEDISH WOMEN; UNITED-STATES; DANISH WOMEN; FOLLOW-UP AB Background: Although most attention regarding the effects of silicone breast implants on cancer risk has focused on breast cancer, there have also been concerns regarding effects on other cancers. This includes malignancies that could occur as a result of foreign-body carcinogenesis (sarcomas) or immune alterations (hematopoietic malignancies), or cancers suggested as possibly elevated on the basis of previous epidemiologic studies (cancers of the cervix, vulva, lung, and brain). Methods: Searches of the English language literature on the topic of silicone breast implants and cancer risk were conducted and reviewed to determine relationships that might have etiologic relevance. Results: Epidemologic studies provide no support for an increased risk of either sarcoma or multiple myeloma among breast implant recipients, disputing clinical and laboratory findings suggesting such a link. Although a number of epidemiologic studies have demonstrated elevated risks of cervical, vulvar, and lung cancers among breast implant patients, it is likely that these excesses relate more to lifestyle characteristics (e.g., cigarette smoking, sexual behavior) than to the effects of the implants. Brain cancer excesses, suggested in one study, have not been confirmed in either an update of the mortality experience in this study or on the basis of other investigations. Conclusions: At present, there is no convincing evidence that breast implants alter the risk of nonbreast malignancies. Breast implant patients should continue to be monitored for longer term risks and to assess whether cancer risk is influenced by various patient and implant characteristics. C1 [Brinton, Louise A.] Natl Canc Inst, Hormonal & Reprod Epidemiol Branch, Rockville, MD 20852 USA. RP Brinton, LA (reprint author), Natl Canc Inst, Hormonal & Reprod Epidemiol Branch, 6120 Execut Blvd,Suite 550,Room 5018, Rockville, MD 20852 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 65 TC 20 Z9 20 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD DEC PY 2007 VL 120 IS 7 SU 1 BP 94S EP 102S DI 10.1097/01.prs.0000286573.72187.6e PG 9 WC Surgery SC Surgery GA 241RP UT WOS:000251673800013 PM 18090818 ER PT J AU Oliver, B AF Oliver, Brian TI Sex, dose, and equality SO PLOS BIOLOGY LA English DT Editorial Material ID DOSAGE COMPENSATION; X-CHROMOSOME; MAMMALS; GENOME C1 [Oliver, Brian] Natl Inst Hlth, NIDDK, Cellular & Dev Biol Lab, Bethesda, MD USA. RP Oliver, B (reprint author), Natl Inst Hlth, NIDDK, Cellular & Dev Biol Lab, Bethesda, MD USA. EM oliver@helix.nih.gov NR 21 TC 7 Z9 7 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2007 VL 5 IS 12 BP 2778 EP 2781 DI 10.1371/journal.pbio.0050340 PG 4 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 244OJ UT WOS:000251874900007 ER PT J AU Buhler, C Borde, V Lichten, M AF Buhler, Cyril Borde, Valerie Lichten, Michael TI Mapping meiotic single-strand DNA reveals a new landscape of DNA double-strand breaks in Saccharomyces cerevisiae SO PLOS BIOLOGY LA English DT Article ID SYNAPTONEMAL COMPLEX-FORMATION; RECOMBINATION HOT-SPOTS; YEAST CHROMOSOME-III; RECA HOMOLOGS RAD51; BUDDING YEAST; ECTOPIC RECOMBINATION; CHROMATIN-STRUCTURE; HUMAN GENOME; MEIOSIS; PROTEIN C1 [Buhler, Cyril; Borde, Valerie; Lichten, Michael] Natl Inst Hlth, Natl Canc Inst, Biochem & Mol Biol Lab, Bethesda, MD USA. RP Lichten, M (reprint author), Natl Inst Hlth, Natl Canc Inst, Biochem & Mol Biol Lab, Bethesda, MD USA. EM lichten@helix.nih.gov RI Borde, Valerie/G-5228-2012; Lichten, Michael/C-5795-2013; OI Lichten, Michael/0000-0001-9707-2956; Buhler, Cyril/0000-0003-0397-7653 FU Intramural NIH HHS NR 89 TC 135 Z9 137 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2007 VL 5 IS 12 BP 2797 EP 2808 AR e324 DI 10.1371/journal.pbio.0050324 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 244OJ UT WOS:000251874900011 PM 18076285 ER PT J AU Kittappa, R Chang, WW Awatramani, RB Mckay, RDG AF Kittappa, Raja Chang, Wendy W. Awatramani, Rajeshwar B. Mckay, Ronald D. G. TI The foxa2 gene controls the birth and spontaneous degeneration of dopamine neurons in old age SO PLOS BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; FORKHEAD TRANSCRIPTION FACTOR; PARKINSONS-DISEASE; FLOOR PLATE; MIDBRAIN; MUTATIONS; DIFFERENTIATION; MECHANISMS; HNF-3-BETA; INDUCTION AB Parkinson disease affects more than 1% of the population over 60 y old. The dominant models for Parkinson disease are based on the use of chemical toxins to kill dopamine neurons, but do not address the risk factors that normally increase with age. Forkhead transcription factors are critical regulators of survival and longevity. The forkhead transcription factor, foxa2, is specifically expressed in adult dopamine neurons and their precursors in the medial floor plate. Gain-and loss-of-function experiments show this gene, foxa2, is required to generate dopamine neurons during fetal development and from embryonic stem cells. Mice carrying only one copy of the foxa2 gene show abnormalities in motor behavior in old age and an associated progressive loss of dopamine neurons. Manipulating forkhead function may regulate both the birth of dopamine neurons and their spontaneous death, two major goals of regenerative medicine. C1 [Kittappa, Raja; Chang, Wendy W.; Mckay, Ronald D. G.] Natl Inst Hlth, NINDS, Mol Biol Lab, Bethesda, MD USA. [Awatramani, Rajeshwar B.] Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL USA. RP Mckay, RDG (reprint author), Natl Inst Hlth, NINDS, Mol Biol Lab, Bethesda, MD USA. EM mckay@codon.nih.gov FU Intramural NIH HHS NR 52 TC 142 Z9 144 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2007 VL 5 IS 12 BP 2875 EP 2884 AR e325 DI 10.1371/journal.pbio.0050325 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 244OJ UT WOS:000251874900017 PM 18076286 ER PT J AU Montefiori, D Sattentau, Q Flores, J Esparza, J Mascola, J AF Montefiori, David Sattentau, Quentin Flores, Jorge Esparza, Jose Mascola, John CA Working Grp Convened Global HIV Va TI Antibody-based HIV-1 vaccines: Recent developments and future directions SO PLOS MEDICINE LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; GP120 ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; SYNERGISTIC NEUTRALIZATION; CD4-BINDING SITE; DENDRITIC CELLS; BINDING-SITE; ENV CLONES; REPLICATION C1 [Montefiori, David] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Sattentau, Quentin] Univ Oxford, Oxford, England. [Flores, Jorge] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Esparza, Jose] Bill & Melinda Gates Fdn, Seattle, WA USA. [Mascola, John] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Montefiori, D (reprint author), Duke Univ, Med Ctr, Durham, NC 27706 USA. EM monte@duke.edu NR 57 TC 63 Z9 63 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD DEC PY 2007 VL 4 IS 12 BP 1867 EP 1871 AR e348 DI 10.1371/journal.pmed.0040348 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 244OG UT WOS:000251874600007 PM 18052607 ER PT J AU Cross, AJ Leitzmann, MF Gail, MH Hollenbeck, AR Schatzkin, A Sinha, R AF Cross, Amanda J. Leitzmann, Michael F. Gail, Mitchell H. Hollenbeck, Albert R. Schatzkin, Arthur Sinha, Rashmi TI A prospective study of red and processed meat intake in relation to cancer risk SO PLOS MEDICINE LA English DT Review ID NON-HODGKINS-LYMPHOMA; N-NITROSO COMPOUNDS; FOOD FREQUENCY QUESTIONNAIRES; MULTICENTER CASE-CONTROL; PROSTATE-CANCER; PANCREATIC-CANCER; DIETARY FACTORS; STOMACH-CANCER; HETEROCYCLIC AMINES; UNITED-STATES AB Background Red meat and processed meat have been associated with carcinogenesis at several anatomic sites, but no prospective study has examined meat intake in relation to a range of malignancies. We investigated whether red or processed meat intake increases cancer risk at a variety of sites. Methods and Findings The National Institutes of Health (NIH)-AARP (formerly the American Association for Retired Persons) Diet and Health Study is a cohort of approximately 500,000 people aged 50-71 y at baseline (1995-1996). Meat intake was estimated from a food frequency questionnaire administered at baseline. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals within quintiles of red and processed meat intake. During up to 8.2 y of follow-up, 53,396 incident cancers were ascertained. Statistically significant elevated risks ( ranging from 20% to 60%) were evident for esophageal, colorectal, liver, and lung cancer, comparing individuals in the highest with those in the lowest quintile of red meat intake. Furthermore, individuals in the highest quintile of processed meat intake had a 20% elevated risk for colorectal and a 16% elevated risk for lung cancer. Conclusions Both red and processed meat intakes were positively associated with cancers of the colorectum and lung; furthermore, red meat intake was associated with an elevated risk for cancers of the esophagus and liver. C1 [Cross, Amanda J.; Leitzmann, Michael F.; Schatzkin, Arthur; Sinha, Rashmi] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA. [Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Cross, AJ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA. EM crossa@mail.nih.gov RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU Intramural NIH HHS NR 117 TC 189 Z9 190 U1 7 U2 49 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD DEC PY 2007 VL 4 IS 12 BP 1973 EP 1984 AR e325 DI 10.1371/journal.pmed.0040325 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 244OG UT WOS:000251874600019 PM 18076279 ER PT J AU Lipner, EM Law, MA Barnett, E Keystone, JS von Sonnenburg, F Loutan, L Prevots, DR Klion, AD Nutman, TB AF Lipner, Ettie M. Law, Melissa A. Barnett, Elizabeth Keystone, Jay S. von Sonnenburg, Frank Loutan, Louis Prevots, D. Rebecca Klion, Amy D. Nutman, Thomas B. CA GeoSentinel Surveillance Network TI Filariasis in Travelers Presenting to the GeoSentinel Surveillance Network SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID LOA-LOA INFECTION; HYPERRESPONSIVE SYNDROME; NONENDEMIC POPULATIONS; CLINICAL PRESENTATION; LOIASIS; ONCHOCERCIASIS; ANGIOEDEMA; DISEASE AB Background: As international travel increases, there is rising exposure to many pathogens not traditionally encountered in the resource-rich countries of the world. Filarial infections, a great problem throughout the tropics and subtropics, are relatively rare among travelers even to filaria-endemic regions of the world. The GeoSentinel Surveillance Network, a global network of medicine/travel clinics, was established in 1995 to detect morbidity trends among travelers. Principal Findings: We examined data from the GeoSentinel database to determine demographic and travel characteristics associated with filaria acquisition and to understand the differences in clinical presentation between nonendemic visitors and those born in filaria-endemic regions of the world. Filarial infections comprised 0.62% (n = 271) of all medical conditions reported to the GeoSentinel Network from travelers; 37% of patients were diagnosed with Onchocerca volvulus, 25% were infected with Loa loa, and another 25% were diagnosed with Wuchereria bancrofti. Most infections were reported from immigrants and from those immigrants returning to their county of origin ( those visiting friends and relatives); the majority of filarial infections were acquired in sub-Saharan Africa. Among the patients who were natives of filaria-nonendemic regions, 70.6% acquired their filarial infection with exposure greater than 1 month. Moreover, nonendemic visitors to filaria-endemic regions were more likely to present to GeoSentinel sites with clinically symptomatic conditions compared with those who had lifelong exposure. Significance: Codifying the filarial infections presenting to the GeoSentinel Surveillance Network has provided insights into the clinical differences seen among filaria-infected expatriates and those from endemic regions and demonstrated that O. volvulus infection can be acquired with short-term travel. C1 [Lipner, Ettie M.; Prevots, D. Rebecca] NIAID, Off Global Res, NIH, Bethesda, MD 20892 USA. [Law, Melissa A.; Klion, Amy D.; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Barnett, Elizabeth] Boston Univ, Med Ctr, Div Travel & Int Hlth, Boston, MA USA. [Keystone, Jay S.] Univ Toronto, Div Infect Dis, Toronto, ON, Canada. [von Sonnenburg, Frank] Univ Munich, Dept Trop & Infect Dis, Munich, Germany. [Loutan, Louis] Univ Hosp Geneva, Dept Community Med, Travel & Migrat Med Unit, Geneva, Switzerland. RP Lipner, EM (reprint author), NIAID, Off Global Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tnutman@niaid.nih.gov OI Barnett, Elizabeth/0000-0003-4822-5949; Klion, Amy/0000-0002-4986-5326 FU Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institutes of Health and GeoSentinel FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health and GeoSentinel, The Global Surveillance Network of the International Society of Travel Medicine through a Cooperative Agreement U50/CCU412347 from the Centers for Disease Control and Prevention. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 17 TC 35 Z9 35 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD DEC PY 2007 VL 1 IS 3 AR e88 DI 10.1371/journal.pntd.0000088 PG 7 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 383XK UT WOS:000261707500003 PM 18160987 ER PT J AU Fauci, AS AF Fauci, Anthony S. TI Maurice R. Hilleman - 30 August 1919 . 11 April 2005 SO PROCEEDINGS OF THE AMERICAN PHILOSOPHICAL SOCIETY LA English DT Biographical-Item C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER PHILOSOPHICAL SOC PI PHILADELPHIA PA 104 SOUTH FIFTH ST, PHILADELPHIA, PA 19106-3387 USA SN 0003-049X J9 P AM PHILOS SOC JI Proc. Amer. Philos. Soc. PD DEC PY 2007 VL 151 IS 4 BP 451 EP 455 PG 5 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA 285GJ UT WOS:000254765000010 ER PT J AU Schiffmann, SN Fisone, G Moresco, R Cunha, RA Ferre, S AF Schiffmann, S. N. Fisone, G. Moresco, R. Cunha, R. A. Ferre, S. TI Adenosine A(2A) receptors and basal ganglia physiology SO PROGRESS IN NEUROBIOLOGY LA English DT Article; Proceedings Paper CT International Research Conference on Targeting Adenosine A2A Receptons in Parkinson's Disease and other CNS Disorders CY MAY 17-19, 2006 CL Boston, MA SP US Army Mil Res Mat Command DE adenosine A(2A) receptor; dopamine receptors; metabotropic glutamate receptors; GABAergic enkephalinergic neuron; heteromeric receptor complexes; striatum ID STRIATAL PROJECTION NEURONS; RAT NEOSTRIATAL NEURONS; LONG-TERM POTENTIATION; EXCITATORY SYNAPTIC-TRANSMISSION; CAMP-REGULATED PHOSPHOPROTEIN; POSITRON-EMISSION-TOMOGRAPHY; DOPAMINE D-1 RECEPTORS; CENTRAL-NERVOUS-SYSTEM; GATED SODIUM CURRENT; MEDIUM SPINY NEURONS AB Adenosine A(2A) receptors are highly enriched in the basal ganglia system. They are predominantly expressed in enkephalin-expressing GABAergic striatopallidal neurons and therefore are highly relevant to the function of the indirect efferent pathway of the basal ganglia system. In these GABAergic enkephalinergic neurons, the A(2A) receptor tightly interacts structurally and functionally with the dopamine D-2 receptor. Both by forming receptor heteromers and by targeting common intracellular signaling cascades, A(2A) and D2 receptors exhibit reciprocal antagonistic interactions that are central to the function of the indirect pathway and hence to basal ganglia control of movement, motor learning, motivation and reward. Consequently, this A(2A)/D-2 receptors antagonistic interaction is also central to basal ganglia dysfunction in Parkinson's disease. However, recent evidence demonstrates that, in addition to this post-synaptic site of action, striatal A(2A) receptors are also expressed and have physiological relevance on pre-synaptic glutamatergic terminals of the cortico-limbic-striatal and thalamo-striatal pathways, where they form heteromeric receptor complexes with adenosine A(1) receptors. Therefore, A(2A) receptors play an important fine-tuning role, boosting the efficiency of glutamatergic information flow in the indirect pathway by exerting control, either pre- and/or post-synaptically, over other key modulators of glutamatergic synapses, including D-2 receptors, group I metabotropic mGIU(5) glutamate receptors and cannabinoid CB1 receptors, and by triggering the cAMP-protein kinase A signaling cascade. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Libre Bruxelles, Neurophysiol Lab, B-1070 Brussels, Belgium. [Fisone, G.] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. [Moresco, R.] Univ Milan, CNR, San Raffaele Sci Inst, Milan, Italy. [Cunha, R. A.] Univ Coimbra, Fac Med, Ctr Neurosci, Inst Biochem, P-3004504 Coimbra, Portugal. [Ferre, S.] NIH, Natl Inst Drug Abuse, Dept Hlth & Human Serv, Behav Neurosci Branch, Baltimore, MD 21224 USA. RP Schiffmann, SN (reprint author), Univ Libre Bruxelles, Neurophysiol Lab, Campus Erasme,808 route Lennik,CP601, B-1070 Brussels, Belgium. EM sschiffm@ulb.ac.be RI Ferre, Sergi/K-6115-2014; Cunha, Rodrigo/E-7475-2015 OI Ferre, Sergi/0000-0002-1747-1779; Cunha, Rodrigo/0000-0003-2550-6422 FU Intramural NIH HHS [Z01 DA000493-02, Z99 DA999999] NR 142 TC 187 Z9 190 U1 1 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD DEC PY 2007 VL 83 IS 5 BP 277 EP 292 DI 10.1016/j.pneurobio.2007.05.001 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 244RH UT WOS:000251882500003 PM 17646043 ER PT J AU Ferre, S Diamond, I Goldberg, SR Yao, L Hourani, SMO Huang, ZL Urade, Y Kitchen, I AF Ferre, S. Diamond, I. Goldberg, S. R. Yao, L. Hourani, S. M. O. Huang, Z. L. Urade, Y. Kitchen, I. TI Adenosine A(2A) receptors in ventral striatum, hypothalamus and nociceptive circuitry - Implications for drug addiction, sleep and pain SO PROGRESS IN NEUROBIOLOGY LA English DT Article; Proceedings Paper CT International Research Conference on Targeting Adenosine A2A Receptons in Parkinson's Disease and other CNS Disorders CY MAY 17-19, 2006 CL Boston, MA SP US Army Mil Res Mat Command DE adenosine A(2A) receptor; striatum; hypothalamus; peripheral nervous system; drug addiction; sleep; pain ID CENTRAL-NERVOUS-SYSTEM; VENTROLATERAL PREOPTIC NEURONS; CANNABINOID CB1 RECEPTORS; COCAINE-SEEKING BEHAVIOR; PROSTAGLANDIN-D SYNTHASE; G-PROTEIN SIGNALING-3; BETA-GAMMA DIMERS; A(2A) RECEPTORS; NUCLEUS-ACCUMBENS; SPINAL-CORD AB Adenosine A(2A) receptors localized in the dorsal striatum are considered as a new target for the development of antiparkinsonian drugs. Co-administration of A(2A) receptor antagonists has shown a significant improvement of the effects Of L-DOPA. The present review emphasizes the possible application of A(2A) receptor antagonists in pathological conditions other than parkinsonism, including drug addiction, sleep disorders and pain. In addition to the dorsal striatum, the ventral striatum (nucleus accumbens) contains a high density of A(2A) receptors, which presynaptically and postsynaptically regulate glutamatergic transmission in the cortical glutamatergic projections to the nucleus accumbens. It is currently believed that molecular adaptations of the cortico-accumbens glutamatergic synapses are involved in compulsive drug seeking and relapse. Here we review recent experimental evidence suggesting that A(2A) antagonists could become new therapeutic agents for drug addiction. Morphological and functional studies have identified lower levels of A(2A) receptors in brain areas other than the striatum, such as the ventrolateral preoptic area of the hypothalamus, where adenosine plays an important role in sleep regulation. Although initially believed to be mostly dependent on A(1) receptors, here we review recent studies that demonstrate that the somnogenic effects of adenosine are largely mediated by hypothalamic A(2A) receptors. A(2A) receptor antagonists could therefore be considered as a possible treatment for narcolepsy and other sleep-related disorders. Finally, nociception is another adenosine-regulated neural function previously thought to mostly involve A(1) receptors. Although there is some conflicting literature on the effects of agonists and antagonists, which may partly be due to the lack of selectivity of available drugs, the studies in A(2A) receptor knockout mice suggest that A(2A) receptor antagonists might have some therapeutic potential in pain states, in particular where high intensity stimuli are prevalent. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Ferre, S.; Goldberg, S. R.] Natl Inst Drug Abuse, Dept Hlth & Human Serv, Intramural Res Program, Preclin Pharmacol Sect, Baltimore, MD 21224 USA. [Diamond, I.; Yao, L.] CV Therapeut Inc, Palo Alto, CA 94304 USA. [Hourani, S. M. O.; Kitchen, I.] Univ Surrey, Sch Biol & Mol Sci, Pharmacol Grp, Guildford GU2 7XH, Surrey, England. [Huang, Z. L.; Urade, Y.] Osaka Biosci Inst, Osaka 5650874, Japan. [Huang, Z. L.] Fudan Univ, Shanghai Med Coll, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. RP Ferre, S (reprint author), Natl Inst Drug Abuse, Dept Hlth & Human Serv, Intramural Res Program, Preclin Pharmacol Sect, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Ferre, Sergi/K-6115-2014 OI Ferre, Sergi/0000-0002-1747-1779 FU Intramural NIH HHS [Z01 DA000493-02] NR 185 TC 65 Z9 68 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD DEC PY 2007 VL 83 IS 5 BP 332 EP 347 DI 10.1016/j.pneurobio.2007.04.002 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 244RH UT WOS:000251882500006 PM 17532111 ER PT J AU Hebben, M Brants, J Birck, C Samama, JP Wasylyk, B Speliner, D Pradeau, K Domi, A Moss, B Schultz, P Drillien, R AF Hebben, Matthias Brants, Jan Birck, Catherine Samama, Jean-Pierre Wasylyk, Bohdan Speliner, Danile Pradeau, Karine Domi, Arban Moss, Bernard Schultz, Patrick Drillien, Robert TI High level protein expression in mammalian cells using a safe viral vector: Modified vaccinia virus Ankara SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE vaccinia virus; modified vaccinia virus Ankara (MVA); bacteriophage T7; protein expression; tubulin tyrosine ligase ID BACTERIOPHAGE-T7 RNA-POLYMERASE; GENE-EXPRESSION; RECOMBINANT VIRUSES; STRAIN MVA; SYSTEM; REPLICATION; POXVIRUSES; TRANSIENT; SELECTION; SEQUENCE AB Vaccinia virus vectors are attractive tools to direct high level protein synthesis in mammalian cells. In one of the most efficient strategies developed so far, the gene to be expressed is positioned downstream of a bacteriophage T7 promoter within the vaccinia genome and transcribed by the T7 RNA polymerase, also encoded by the vaccinia virus genome. Tight regulation of transcription and efficient translation are ensured by control elements of the Escherichia coli lactose operon and the encephalomyocarditis virus leader sequence, respectively. We have integrated such a stringently controlled expression system, previously used successfully in a standard vaccinia virus backbone, into the modified vaccinia virus Ankara strain (MVA). In this manner, proteins of interest can be produced in mammalian cells under standard laboratory conditions because of the inherent safety of the MVA strain. Using this system for expression of P-galactosidase, about 15 mg protein could be produced from 10(8) BHK21 cells over a 24-h period, a value 4-fold higher than the amount produced from an identical expression system based on a standard vaccinia virus strain. In another application, we employed the MVA vector to produce human tubulin tyrosine ligase and demonstrate that this protein becomes a major cellular protein upon induction conditions and displays its characteristic enzymatic activity. The MVA vector should prove useful for many other applications in which mammalian cells are required for protein production. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Strasbourg 1, INSERM U596, CNRS UMR7104, Inst Genet Biol Mol & Cellulaire, F-67404 Strasbourg, France. NIH, NIAID, Lab Viral Dis, Bethesda, MD USA. RP Drillien, R (reprint author), Univ Strasbourg 1, INSERM U596, CNRS UMR7104, Inst Genet Biol Mol & Cellulaire, 1 Rue Laurent Fries, F-67404 Strasbourg, France. EM drillien@igbmc.u-strasbg.fr OI WASYLYK, Bohdan/0000-0002-1718-1237 NR 31 TC 8 Z9 9 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD DEC PY 2007 VL 56 IS 2 BP 269 EP 278 DI 10.1016/j.pep.2007.08.003 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 236OK UT WOS:000251312300016 PM 17892951 ER PT J AU Moulaei, T Botos, I Ziolkowska, NE Bokesch, HR Krumpe, LR Mckee, TC O'Keefe, BR Dauter, Z Wlodawer, A AF Moulaei, Tinoush Botos, Istvan Ziolkowska, Natasza E. Bokesch, Heidi R. Krumpe, Lauren R. Mckee, Tawnya C. O'Keefe, Barry R. Dauter, Zbigniew Wlodawer, Alexander TI Atomic-resolution crystal structure of the antiviral lectin scytovirin SO PROTEIN SCIENCE LA English DT Article DE lectins; new fold; anomalous scattering; scytovirin ID CYANOBACTERIUM SCYTONEMA-VARIUM; ANTI-HIV PROTEIN; POTENT; REFINEMENT AB The crystal structures of the natural and recombinant antiviral lectin scytovirin (SVN) were solved by single-wavelength anomalous scattering and refined with data extending to 1.3 angstrom and 1.0 angstrom resolution, respectively. A molecule of SVN consists of a single chain 95 amino acids long, with an almost perfect sequence repeat that creates two very similar domains (RMS deviation 0.25 angstrom for 40 pairs of C alpha atoms). The crystal structure differs significantly from a previously published NMR structure of the same protein, with the RMS deviations calculated separately for the N- and C-terminal domains of 5.3 angstrom and 3.7 angstrom, respectively, and a very different relationship between the two domains. In addition, the disulfide bonding pattern of the crystal structures differs from that described in the previously published mass spectrometry and NMR studies. C1 NCI, Macromol Crystallog Lab, Prot Struct Sect, Ft Detrick, MD 21702 USA. NCI, Ctr Canc Res, Mol Targets Dev Program, Ft Detrick, MD 21702 USA. NCI, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. Argonne Natl Lab, Natl Canc Inst, Macromol Crystallog Lab, Synchrotron Radiat Res Sect, Argonne, IL 60439 USA. RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Ft Detrick, MD 21702 USA. EM wlodawer@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01-CO-12400] NR 15 TC 13 Z9 14 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD DEC PY 2007 VL 16 IS 12 BP 2756 EP 2760 DI 10.1110/ps.073157507 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 233HK UT WOS:000251081300021 PM 17965185 ER PT J AU Schneidman-Duhovny, D Nussinov, R Wolfson, HJ AF Schneidman-Duhovny, Dina Nussinov, Ruth Wolfson, Haim J. TI Automatic prediction of protein interactions with large scale motion SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article; Proceedings Paper CT 3rd CAPRI Evaluation Meeting CY APR 20-21, 2007 CL Toronto, CANADA DE docking; flexibility; hinge motion; large scale motion ID NORMAL-MODE ANALYSIS; RIGID-BODY DOCKING; MACROMOLECULAR MOTIONS; RECEPTOR FLEXIBILITY; LIGAND DOCKING; DYNAMICS; CAPRI; CONFORMATIONS; OPTIMIZATION; REFINEMENT AB Proteins often change their conformation upon binding to other molecules. Taking these conformational changes into account in docking is an extremely difficult task: the larger the scale of the motion the harder it is to predict the structure of the association complex. Here, we present a fully automated method for flexible docking with large scale motion in one of the docked molecules. The method automatically identifies hinge regions and rigid parts and then docks the input molecules while explicitly considering the hinges and possible protein motions. C1 Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. SAIC Frederick Inc, NCI Frederick, Ctr Canc Res Nanobiol Program, Basic Res Programs, Ft Detrick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Schneidman-Duhovny, D (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM duhovka@post.tau.ac.il; wolfson@post.tau.ac.il RI Wolfson, Haim/A-1837-2011 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [1UC1AI067231] NR 49 TC 37 Z9 39 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD DEC PY 2007 VL 69 IS 4 BP 764 EP 773 DI 10.1002/prot.21759 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 235ZJ UT WOS:000251272500010 PM 17886339 ER PT J AU Turkel, S Pao, M AF Turkel, Susan Pao, Maryland TI Late consequences of chronic pediatric illness SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CONGENITAL HEART-DISEASE; JUVENILE IDIOPATHIC ARTHRITIS; CHRONIC PHYSICAL ILLNESS; GROWTH-HORMONE TREATMENT; HEALTH-CARE SYSTEMS; CYSTIC-FIBROSIS; RHEUMATIC-DISEASE; LINEAR GROWTH; ADULT CARE AB With the advent of new treatments for chronic pediatric disorders such as cystic fibrosis (CF), juvenile rheumatoid arthritis, and congenital heart disease, more children and adolescents are surviving into adulthood than ever before. Seventy years ago, individuals who had CF survived an average of 5 years; currently the life expectancy for CF is more than 30 years [1]. Increased survival has brought new morbidities [2] and may affect psychosocial outcomes of adult life [3]. The prevalence of children suffering from a chronic illness varies widely, but the overall rate is 10% to 20% [4]. Children who have chronic illnesses are more likely to have emotional, behavioral, and psychiatric symptoms than healthy children [5] and may be psychologically affected or traumatized by medical treatments [6]. On the other hand, resilience is common [7], and chronically ill children do not inevitably develop psychiatric difficulties. This article is aimed at helping psychiatric consultants understand how medical, developmental, and psychosocial. needs are altered in adults who have grown up with chromic pediatric illnesses. Three childhood conditions, congenital heart disease, CF, and rheumatologic disorders, are discussed in detail. These conditions are used as models to illustrate the impact of congenital malformations, genetic disorders, and typically adult disorders occurring in the pediatric age group. C1 NIMH, Off Clin Director, NIH, Bethesda, MD 20892 USA. Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. RP Turkel, S (reprint author), NIMH, Off Clin Director, NIH, Bldg 10,Room 6-5340,10 Ctr Dr, Bethesda, MD 20892 USA. EM paom@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 96 TC 39 Z9 41 U1 2 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2007 VL 30 IS 4 BP 819 EP + DI 10.1016/j.psc.2007.07.009 PG 18 WC Psychiatry SC Psychiatry GA 233BW UT WOS:000251066400013 PM 17938047 ER PT J AU Flory, JD Xu, K New, AS Finch, T Goldman, D Siever, LJ AF Flory, Janine D. Xu, Ke New, Antonia S. Finch, Thembi Goldman, David Siever, Larry J. TI Irritable assault and variation in the COMT gene SO PSYCHIATRIC GENETICS LA English DT Article DE aggression; axis II personality disorders; COMT ID O-METHYLTRANSFERASE POLYMORPHISM; AGGRESSIVE-BEHAVIOR; FUNCTIONAL POLYMORPHISM; SCHIZOPHRENIA; ASSOCIATION; METAANALYSIS; HOSTILITY; HAPLOTYPE; ALLELE; MAOA AB Aggression is associated with the 'low' activity allele (Met) of the functional Val(158)Met polymorphism among people with schizophrenia spectrum disorders relative to the 'high' activity (Val) allele. We examined this polymorphism in a sample of 112 people with axis II personality disorders. Participants completed the Buss Durkee Hostility Inventory. Two single nucleotide polymorphisms in the COMT gene were genotyped in these participants classified as 'white' according to US Census Bureau definitions. We failed to observe an association between the Val(158)Met allele and aggression but observed an association between self-reported aggression and the G allele of a biallelic polymorphism located in the 3 '' UTR (rs16559). This allele is less prevalent among schizophrenics and is associated with lower COMT expression in the brain. These findings provide limited support for a role of COMT in modulating aggressive behavior, and are extended to people with personality disorders. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. NIMH, NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Flory, JD (reprint author), Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. EM janine.flory@mssm.edu RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NCRR NIH HHS [M01 RR00071]; NIMH NIH HHS [MH 10995, MH063875] NR 22 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD DEC PY 2007 VL 17 IS 6 BP 344 EP 346 PG 3 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 227ZB UT WOS:000250695400005 PM 18075475 ER PT J AU Tuma, F AF Tuma, Farris TI Mass trauma intervention: A case for integrating principles of behavioral health with intervention to restore physical safety, order, and infrastructure SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Editorial Material C1 NIMH, Traumat Stress Disorders Res Program, Methesda, MD USA. RP Tuma, F (reprint author), NIMH, Traumat Stress Disorders Res Program, 6001 Execut Blvd,Room 711,MSC 9632, Methesda, MD USA. EM ftuma@mail.nih.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD WIN PY 2007 VL 70 IS 4 BP 358 EP 360 PG 3 WC Psychiatry SC Psychiatry GA 249NX UT WOS:000252236600009 ER PT J AU Fox, MA Andrews, AM Wendland, JR Lesch, KP Holmes, A Murphy, DL AF Fox, Meredith A. Andrews, Anne M. Wendland, Jens R. Lesch, Klaus-Peter Holmes, Andrew Murphy, Dennis L. TI A pharmacological analysis of mice with a targeted disruption of the serotonin transporter SO PSYCHOPHARMACOLOGY LA English DT Review DE serotonin; serotonin transporter (SERT); knockout mice; pharmacology ID KNOCK-OUT MICE; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CONDITIONED PLACE PREFERENCE; TAIL SUSPENSION TEST; EARLY-LIFE BLOCKADE; 5-HT TRANSPORTER; NEUROENDOCRINE RESPONSES; BRAIN-SEROTONIN; DEFICIENT MICE; 1-METHYL-4-(2'-AMINOPHENYL)-1,2,3,6-TETRAHYDROPYRIDINE 2'-NH2-MPTP AB Rationale Partial or complete ablation of serotonin transporter (SERT) expression in mice leads to altered responses to serotonin receptor agonists and other classes of drugs. Objectives In the current report, we review and integrate many of the major behavioral, physiological, and neurochemical findings in the current literature regarding pharmacological assessments made in SERT mutant mice. Results The absence of normal responses to serotonin reuptake inhibiting (SRI)antidepressants in SERT knockout (-/-) mice demonstrates that actions on SERT are a critical principle mechanism of action of members of this class of antidepressants. Drugs transported by SERT, (+)-3,4-methylenedioxymethamphetamine (MDMA) and 1-methyl-4-(2 '-aminophenyl)-1,2,3,6-tetrahydropyridine (2 '-NH2-MPTP), are also inactive in SERT -/- mice. Temperature, locomotor, and electrophysiological responses to various serotonin receptor agonists, including 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT), ipsapirone, and RU24969, are reduced in SERT -/- mice, despite comparatively lesser reductions in Htr1a and Htr1b binding sites, G-proteins, and other signaling molecules. SERT -/- mice exhibit an similar to 90% reduction in head twitches in response to the Htr2a/2c agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), associated with a profound reduction in arachidonic acid signaling, yet only modest changes in Htr2a and Htr2c binding sites. SERT -/- mice also exhibit altered behavioral responses to cocaine and ethanol, related to abnormal serotonin, and possibly dopamine and norepinephrine, homeostasis. Conclusions Together, these studies demonstrate a complex and varied array of modified drug responses after constitutive deletion of SERT and provide insight into the role of serotonin, and in particular, its transporter, in the modulation of complex behavior and in the pharmacological actions of therapeutic agents and drugs of abuse. C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA. Univ Wurzburg, Dept Psychiat & Psychotherapy, D-97080 Wurzburg, Germany. NIAAA, Lab Integrat Neurosci, Sect Behav Sci & Genet, Bethesda, MD 20852 USA. RP Fox, MA (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10,Room 3D41, Bethesda, MD 20892 USA. EM mfox@mail.nih.gov RI Andrews, Anne/B-4442-2011; Wendland, Jens/A-1809-2012; Lesch, Klaus-Peter/J-4906-2013 OI Andrews, Anne/0000-0002-1961-4833; Lesch, Klaus-Peter/0000-0001-8348-153X FU Intramural NIH HHS NR 109 TC 36 Z9 37 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2007 VL 195 IS 2 BP 147 EP 166 DI 10.1007/s00213-007-0910-0 PG 20 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 226MW UT WOS:000250594200001 PM 17712549 ER PT J AU Zhai, HF Zhang, ZY Zhao, M Qiu, Y Ghitza, UE Lu, L AF Zhai, Hai-feng Zhang, Zhang-Yin Zhao, Mei Qiu, Yi Ghitza, Udi E. Lu, Lin TI Conditioned drug reward enhances subsequent spatial learning and memory in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE morphine; cocaine; sucrose; conditioned reward; conditioned aversion; spatial learning ID INTRACRANIAL SELF-STIMULATION; VENTRAL TEGMENTAL AREA; PLACE-PREFERENCE; D-AMPHETAMINE; OPIATE WITHDRAWAL; INTRAACCUMBENS AMPHETAMINE; INCENTIVE-SENSITIZATION; REPEATED PRETREATMENT; HIPPOCAMPAL-LESIONS; NUCLEUS-ACCUMBENS AB Rationale Chronic exposure to drugs of abuse alters neural processes that normally promote learning and memory. A context that is repeatedly paired with reinforcing drugs will acquire secondary reinforcing properties (conditioned reward). However, the effects of conditioned reward on spatial learning are unknown. Objective Using the conditioned place preference procedure and Morris water maze task, we examined the role of conditioned reward or aversion in spatial learning. Materials and methods Groups of rats acquired morphine (10 mg/kg), cocaine (10 mg/kg), or oral sucrose (15%) conditioned place preference (CPP). Another group of morphine-dependent rats acquired conditioned place aversion (CPA) to a context paired with precipitated opiate withdrawal induced by naloxone injections (1 mg/kg). To examine the role of conditioned reward or aversion in spatial learning, rats were then exposed to the previously morphine-, cocaine-, sucrose- or naloxone-paired context for 10 min before training of spatial learning in the Morris water maze. Results Exposure to the morphine- or cocaine- paired but not the sucrose- or the naloxone-paired context decreased the latency to find the platform in the Morris water maze test. Conclusions Our results provide the first evidence that conditioned drug reward promotes spatial learning. We speculate that this enhancement of spatial learning by the drug-paired context may promote contextual-cue-induced relapse to drug taking by facilitating exploratory drugseeking behaviors. C1 Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA. Natl Inst Drug Abuse, NIH, Baltimore, MD 21224 USA. RP Lu, L (reprint author), Peking Univ, Natl Inst Drug Dependence, 38 Xue Yuan Rd,HaiDian Dist, Beijing 100083, Peoples R China. EM linlu@bjmu.edu.cn FU Intramural NIH HHS NR 62 TC 12 Z9 15 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2007 VL 195 IS 2 BP 193 EP 201 DI 10.1007/s00213-007-0893-x PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 226MW UT WOS:000250594200005 PM 17661018 ER PT J AU Marinelli, PW Funk, D Juzytsch, W Harding, S Rice, KC Shaham, Y Le, AD AF Marinelli, Peter W. Funk, Douglas Juzytsch, Walter Harding, Stephen Rice, Kenner C. Shaham, Yavin Le, A. D. TI The CRF1 receptor antagonist antalarmin attenuates yohimbine-induced increases in operant alcohol self-administration and reinstatement of alcohol seeking in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE alcohol self administration; alpha-2 adrenoceptors; corticosterone; CRF; CRF1 receptor; relapse; reinstatement; stress; noradrenaline ID CORTICOTROPIN-RELEASING-FACTOR; STRESS-INDUCED RELAPSE; ANXIOGENIC DRUG YOHIMBINE; ANXIETY-LIKE BEHAVIOR; PRIMING-INDUCED REINSTATEMENT; ETHANOL-DEPENDENT RATS; COCAINE-SEEKING; FOOD-SEEKING; NORADRENERGIC MECHANISMS; STRIA TERMINALIS AB Rationale and objectives Yohimbine is an alpha-2 adrenoreceptor antagonist that provokes stress- and anxiety-like responses in both humans and laboratory animals. In rats, yohimbine increases operant alcohol self-administration and reinstates alcohol seeking. In this study, we assess whether these effects of yohimbine are attenuated by systemic injections of the corticotrotropin-releasing factor 1 (CRF1) receptor antagonist antalarmin. Materials and methods In Exp. 1, we trained rats to lever press for alcohol solutions (12% w/v, 1 h/day) over several weeks; during training, the response requirement was increased from a fixed-ratio-1 (FR-1) to a fixed-ratio-3 (FR-3) reinforcement schedule. We then tested the effect of antalarmin (10 or 20 mg/kg) on yohimbine (1.25 mg/kg)-induced increases in operant alcohol self-administration (FR-3 reinforcement schedule). Subsequently, we assessed the effect of antalarmin on yohimbine-induced increases in plasma corticosterone levels in the previously self-administering rats. In Exp. 2, we trained the rats to self-administer alcohol as in Exp. 1, and after extinction of the alcohol-reinforced lever responding over 13 days, we tested antalarmin's effect on yohimbine-induced reinstatement of alcohol seeking. Results Yohimbine increased operant alcohol self-administration and reinstated alcohol seeking after extinction. These effects of yohimbine were attenuated by antalarmin. Antalarmin injections in the absence of yohimbine had no effect on either operant alcohol self-administration or extinction responding. Antalarmin had no effect on yohimbine-induced corticosterone release in alcohol-experienced rats. Conclusions These results suggest that extrahypothalamic CRF1 receptors are involved in the effect of yohimbine on operant alcohol self-administration and on relapse to alcohol seeking and support the notion that CRF1 receptor antagonists should be considered in alcohol addiction treatment. C1 CAMH, Dept Neurosci, Toronto, ON M5S 2S1, Canada. Ctr Addict & Mental Hlth, Neurobiol Alcohol Lab, Dept Neurosci, Toronto, ON, Canada. Intramural Res Program, Natl Inst Drug Abuse, Natl Inst Hlth, Dept Hlth & Human Serv, Baltimore, MD USA. Univ Toronto, Dept Pharmacol, Toronto, ON, Canada. Univ Toronto, Dept Psychiat, Toronto, ON, Canada. RP Marinelli, PW (reprint author), CAMH, Dept Neurosci, 33 Russell St, Toronto, ON M5S 2S1, Canada. EM peter_marinelli@camh.net RI shaham, yavin/G-1306-2014 NR 85 TC 113 Z9 116 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2007 VL 195 IS 3 BP 345 EP 355 DI 10.1007/s00213-007-0905-x PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 232EH UT WOS:000251000600005 PM 17705061 ER PT J AU Hoffman, JM Gambhir, SS Kelloff, GJ AF Hoffman, John M. Gambhir, Sanjiv S. Kelloff, Gary J. TI Regulatory and reimbursement challenges for molecular imaging SO RADIOLOGY LA English DT Article ID ONCOLOGIC DRUG DEVELOPMENT; HEALTH-CARE COSTS; CLINICAL-RESEARCH; DECISION-MAKING; DISCOVERY; MEDICARE; COVERAGE; PROGRESS; PROMISE; PROBES AB Molecular imaging is being hailed as the next great advance for imaging. Since molecular imaging typically involves the use of specific imaging probes that are treated like drugs, they will require regulatory approval. As with any drug, molecular imaging probes and techniques will also require thorough assessment in clinical trials to show safety and efficacy. The timeline for the regulatory approval will be long and potentially problematic because of the mounting costs of obtaining final regulatory approval. The current article is a detailed review of the regulatory and reimbursement process that will be required for molecular imaging probes and techniques to become a widespread clinical reality. The role of molecular imaging in the therapeutic drug discovery process will also be reviewed, as this is where these exciting new techniques have the potential to revolutionize the drug discovery and development process and, it is hoped, make it less costly. [F-18] fluoro-2-deoxy-2-D-glucose positron emission tomography, one of the first molecular imaging techniques to be widely used, will be used as an example to illustrate the process of obtaining eventual reimbursement for widespread clinical use. C1 Univ Utah, Sch Med, Dept Radiol & Neurol, Salt Lake City, UT 84112 USA. Stanford Univ, BioX Program, Dept Radiol & Bioengn, Stanford, CA 94305 USA. NIH, NCI, Div Canc Treatment & Diagnost, Bethesda, MD USA. RP Hoffman, JM (reprint author), Univ Utah, Sch Med, Dept Radiol & Neurol, 2000 Circle Hope,Suite 2121, Salt Lake City, UT 84112 USA. NR 55 TC 21 Z9 22 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2007 VL 245 IS 3 BP 645 EP 660 DI 10.1148/radiol.2453060737 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 233DN UT WOS:000251070700006 PM 18024447 ER PT J AU Jeang, KT AF Jeang, Kuan-Teh TI World AIDS Day 2007: AIDS at 26, are we there yet? SO RETROVIROLOGY LA English DT Editorial Material AB This editorial comments on selected progress made in combating the acquired immune deficiency syndrome (AIDS) after 26 years and some of the remaining challenges. C1 NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bethesda, MD 20892 USA. EM kjeang@niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 8 TC 1 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 1 PY 2007 VL 4 AR 86 DI 10.1186/1742-4690-4-86 PG 2 WC Virology SC Virology GA 250BE UT WOS:000252274200001 PM 18053150 ER PT J AU Kostova, Z Tsai, YC Weissman, AM AF Kostova, Zlatka Tsai, Yien Che Weissman, Allan M. TI Ubiquitin ligases, critical mediators of endoplasmic reticulum-associated degradation SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE endoplasmic reticulum-associated degradation; ubiquitin protein ligase (E3); proteasome; Saccharomyces cerevisiae ID AUTOCRINE MOTILITY FACTOR; ER-ASSOCIATED DEGRADATION; PROTEIN-DEGRADATION; MEMBRANE-PROTEIN; AAA-ATPASE; MISFOLDED GLYCOPROTEINS; QUALITY-CONTROL; FACTOR-RECEPTOR; SACCHAROMYCES-CEREVISIAE; MAT-ALPHA-2 REPRESSOR AB Endoplasmic reticulum-associated degradation (ERAD) represents the primary means of quality control within the secretory pathway. Critical to this process are ubiquitin protein ligases (E3s) which, together with ubiquitin conjugating enzymes (E2s), mediate the ubiquitylation of proteins targeted for degradation from the ER. In this chapter we review our knowledge of both Saccharomyces cerevisiae and mammalian ERAD ubiquitin ligases. We focus on recent insights into these E3s, their associated proteins and potential mechanisms of action. Published by Elsevier Ltd. C1 [Kostova, Zlatka; Tsai, Yien Che; Weissman, Allan M.] Natl Canc Inst, Canc Res Ctr, Lab Prot Dynam & Signalling, NIH, Frederick, MD 21702 USA. RP Weissman, AM (reprint author), Natl Canc Inst, Canc Res Ctr, Lab Prot Dynam & Signalling, NIH, Bldg 560 Room 22-103, Frederick, MD 21702 USA. EM amw@nih.gov OI Tsai, Yien Che/0000-0001-9624-1092 FU Intramural NIH HHS [Z01 BC009392-13] NR 90 TC 101 Z9 101 U1 0 U2 9 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD DEC PY 2007 VL 18 IS 6 BP 770 EP 779 DI 10.1016/j.semcdb.2007.09.002 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 267CO UT WOS:000253486700007 PM 17950636 ER PT J AU Chen, Z Laurence, A O'Shea, JJ AF Chen, Zhi Laurence, Arian O'Shea, John J. TI Signal transduction pathways and transcriptional regulation in the control of Th17 differentiation SO SEMINARS IN IMMUNOLOGY LA English DT Review DE signal transduction; transcription factor; chromatin; lymphocyte differentiation; T cells; cytokines ID RECEPTOR ROR-GAMMA; HELPER-CELL-DIFFERENTIATION; GROWTH-FACTOR-BETA; ENCODING INTERFERON-GAMMA; IL-17-PRODUCING T-CELLS; RETINOIC-ACID; TGF-BETA; CUTTING EDGE; AUTOIMMUNE ENCEPHALOMYELITIS; SPHINGOSINE 1-PHOSPHATE AB The discovery of a new lineage of helper T cells that selectively produces interleukin (IL)-17 has provided exciting new insights into immunoregulation, host defense and the pathogenesis of autoimmune diseases. Additionally, the discovery of this T cell subset has offered a fresh look at how the complexity of selective regulation of cytokine gene expression might relate to lineage commitment, terminal differentiation and immunologic memory. Information continues to accumulate on factors that regulate Th17 differentiation at a rapid pace and a few lessons have emerged. Like other lineages, Th17 cells preferentially express a transcription factor, retinoic acid-related orphan receptor (ROR)gamma t, whose expression seems to be necessary for IL-17 production. In addition, signals from the T-cell receptor are a critical aspect of controlling IL-17 production and the transcription factor nuclear factor of activated T cells (NFATs) appears to be another important regulator. IL-6, IL-21 and IL-23 are all cytokines that activate the transcription factor STAT3, which has been established to be necessary for multiple aspects of the biology of Th17 cells. Similarly, TGF beta-1 is important for the differentiation of murine Th17 cells and inducible regulatory T cells (iTregs), but how it exerts its effect on IL-17 gene transcription is unknown and there are data indicating TGF beta-1 is not required for human Th17 differentiation. The extent to which Th17 cells represent terminally differentiated cells or whether they retain plasticity and can develop into another lineage such as IFN gamma secreting Th1 cells is also unclear. Precisely how cytokines produced by this lineage are selectively expressed and selectively extinguished through epigenetic modifications is an area of great importance, but considerable uncertainty. Published by Elsevier Ltd. C1 [Chen, Zhi; Laurence, Arian; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP O'Shea, JJ (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM osheajo@mail.nih.gov RI Laurence, Arian/A-8770-2009 OI Laurence, Arian/0000-0003-0942-8292 FU Intramural NIH HHS [Z01 AR041106-13] NR 84 TC 136 Z9 150 U1 1 U2 8 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD DEC PY 2007 VL 19 IS 6 BP 400 EP 408 DI 10.1016/j.smim.2007.10.015 PG 9 WC Immunology SC Immunology GA 278QU UT WOS:000254302200008 PM 18166487 ER PT J AU Dudley, ME Rosenberg, SA AF Dudley, Mark E. Rosenberg, Steven A. TI Adoptive cell transfer therapy SO SEMINARS IN ONCOLOGY LA English DT Review ID TUMOR-INFILTRATING LYMPHOCYTES; BLOOD MONONUCLEAR-CELLS; MELANOMA ANTIGEN GP100; IN-VIVO PERSISTENCE; METASTATIC MELANOMA; T-CELLS; CANCER REGRESSION; GENE-TRANSFER; LAK CELLS; PHASE-I AB Adoptive cell transfer therapy has developed into a potent and effective treatment for patients with metastatic melanoma. Current application of this therapy relies on the ex vivo generation of highly active, highly avid tumor-reactive lymphocyte cultures from endogenous tumor infiltrating lymphocytes or on the genetic engineering of cells using antigen receptor genes to express de novo tumor antigen recognition. When autologous anti-tumor lymphocyte cultures are administered to patients with high-dose interleukin (IL)-2 following a lymphodepleting conditioning regimen, the cells can expand in vivo, traffic to tumor, and mediate tumor regression and durable objective clinical responses. Current investigation seeks to improve the methods for generating and administering the lymphocyte cultures, and future clinical trials aim to improve durable response rates and extend the patient populations that are candidates for treatment. C1 [Dudley, Mark E.; Rosenberg, Steven A.] Natl Inst Hlth, Surg Branch, Natl Canc Inst, Clin Res Ctr, Bethesda, MD 20892 USA. RP Dudley, ME (reprint author), Natl Inst Hlth, Surg Branch, Natl Canc Inst, Clin Res Ctr, 3-5752,10 Ctr Dr, Bethesda, MD 20892 USA. EM Mark_Dudley@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 33 TC 75 Z9 80 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2007 VL 34 IS 6 BP 524 EP 531 DI 10.1053/j.seminoncol.2007.09.002 PG 8 WC Oncology SC Oncology GA 245YM UT WOS:000251974700011 PM 18083376 ER PT J AU Phillips, EM Odunlami, AO Bonham, VL AF Phillips, Elizabeth M. Odunlami, Adebola O. Bonham, Vence L. TI Mixed race: Understanding difference in the genome era SO SOCIAL FORCES LA English DT Article ID HUMAN GENETIC DIVERSITY; HEALTH DISPARITIES RESEARCH; HEART-FAILURE; DISEASE RISK; 2000 CENSUS; RACE/ETHNICITY; COMPLEXITY; ETHNICITY; HISTORY; IDENTITIES AB This article presents the findings of a qualitative study of multiracial individuals' understanding of identity, race and human genetic variation. The debate regarding the correlation between race, genetics and disease has expanded, but limited empirical data has been collected regarding the lay publics perspective. Participants in this study explore their identity and its relationships to their health care interactions. Participants also share their views on race-based therapeutics, health disparities and the connections between race, ancestry and genetics. Their voices highlight the limitations Of racial categories in describing differences within our increasingly diverse communities. The genomic era will be a pivotal period in challenging current understandings and uses of racial categories in health. C1 [Phillips, Elizabeth M.; Odunlami, Adebola O.; Bonham, Vence L.] NHGRI, NIH, Div Intramural Res, Social Behav Res Branch, Bethesda, MD 20892 USA. RP Bonham, VL (reprint author), NHGRI, NIH, Div Intramural Res, Social Behav Res Branch, 31 Ctr Dr,Room B1B55, Bethesda, MD 20892 USA. EM bonhamv@mail.nih.gov FU Intramural NIH HHS [Z99 HG999999] NR 59 TC 6 Z9 6 U1 0 U2 4 PU UNIV NORTH CAROLINA PRESS PI CHAPEL HILL PA BOX 2288, JOURNALS DEPT, CHAPEL HILL, NC 27515-2288 USA SN 0037-7732 J9 SOC FORCES JI Soc. Forces PD DEC PY 2007 VL 86 IS 2 BP 795 EP 820 PG 26 WC Sociology SC Sociology GA 243UW UT WOS:000251823800016 PM 19079741 ER PT J AU Marler, JR AF Marler, John R. TI NINDS clinical trials in stroke - Lessons learned and future directions SO STROKE LA English DT Article DE clinical trials; stroke ID RANDOMIZED CONTROLLED-TRIAL; ACUTE ISCHEMIC-STROKE; CAROTID-ENDARTERECTOMY; ATRIAL-FIBRILLATION; COMATOSE SURVIVORS; CARDIAC-ARREST; PREVENTION; WARFARIN; ASPIRIN; STENOSIS AB Since 1977 the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH) has sponsored 28 phase 3 trials to evaluate treatments of stroke, which when all completed will have randomized a total of 44 862 patients in the United States and other countries. NINDS stroke clinical trials have been successful in finding beneficial and cost-effective treatments for cerebrovascular disease. Future trials are likely to be larger and have simpler designs which allow for the inclusion of more patients and which collect less data for each patient. In addition, measures of cognitive outcomes, particularly timed tests of executive function, disability scales, and quality-of-life outcomes will become more common. The stroke research community can take pride in the solid base of evidence that has been built over the past 2 decades. If we continue to follow the discoveries of science, continue to create new trial methodology, and increase participation in clinical trials, significant advances in the treatment of cerebrovascular disease will continue. C1 Natl Inst Hlth, Natl Inst Neurolog Disorders & Strokes, Rockville, MD 20892 USA. RP Marler, JR (reprint author), Natl Inst Hlth, Natl Inst Neurolog Disorders & Strokes, 6001 Execut Blvd Rm 2216, Rockville, MD 20892 USA. EM marlerj@ninds.nih.gov NR 23 TC 14 Z9 15 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2007 VL 38 IS 12 BP 3302 EP 3307 DI 10.1161/STROKEAHA.107.485144 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 235OG UT WOS:000251243600033 PM 17962606 ER PT J AU Norvell, JC Berg, JM AF Norvell, John C. Berg, Jeremy M. TI Update on the protein structure initiative SO STRUCTURE LA English DT Editorial Material C1 [Norvell, John C.; Berg, Jeremy M.] NIGMS, NIH, Bethesda, MD 20892 USA. RP Norvell, JC (reprint author), NIGMS, NIH, 45 Ctr Dr 6200, Bethesda, MD 20892 USA. EM norvellj@nigms.nih.gov; bergj@mail.nih.gov OI Berg, Jeremy/0000-0003-3022-0963 NR 0 TC 16 Z9 21 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD DEC PY 2007 VL 15 IS 12 BP 1519 EP 1522 DI 10.1016/i.str.2007.11.004 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 241KN UT WOS:000251655400002 PM 18073099 ER PT J AU Blansfield, JA Choyke, L Morita, SY Choyke, PL Pingpank, JF Alexander, HR Seidel, G Shutack, Y Yuldasheva, N Eugeni, M Bartlett, DL Glenn, GM Middelton, L Linehan, WM Libutti, SK AF Blansfield, Joseph A. Choyke, Lynda Morita, Shane Y. Choyke, Peter L. Pingpank, James F. Alexander, H. Richard Seidel, Geoffrey Shutack, Yvonne Yuldasheva, Nargiza Eugeni, Michelle Bartlett, David L. Glenn, Gladys M. Middelton, Lindsay Linehan, W. Marston Libutti, Steven K. TI Clinical, genetic and radiographic analysis of 108 patients with von Hippel-Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs) SO SURGERY LA English DT Article ID TUMORS; PREVALENCE; MANAGEMENT; LESIONS; CANCER AB Background. von Hippel-Lindau (vHL) disease is an autosomal dominant syndrome associated with neoplasms in multiple organs, which includes the pancreas. Here, we report the greatest single center experience in patients with vHL pancreatic endocrine neoplasm (PNETs). Methods. Between December 1998 and November 2006, 633 patients with vHL were evaluated and those with PAETs were enrolled on a prospective protocol. Results. Overall, 108 vHL patients had PAETs (17%). Nine patients had metastatic disease (8.3%) from their PNET. Patients with lesions greater than 3 cm (n = 25) were more likely to develop metastases than patients with lesions less than 3 cm (n = 83) (P < .005). Thirty-nine patients underwent resection. Germline sequencing showed that 78% of patients with metastases (7/9) had exon 3 mutations compared with 46% of patients without metastases (32/98; P < .01). Tumor doubling time was calculated for the largest PNET The group with metastases had an average tumor doubling. time of 337 days (range, 180-463 days) compared with 2630 days (range, 103-9614 days) for those without metastases (P < .0001). Conclusions. By implementing a system Of selective operative resection based on defined criteria, vHL patients with PNETs can be managed safely. For patients with small primary lesions (< 3 cm), without a mutation of exon 3 and slow tumor doubling time (> 500 days), a nonoperative approach may be appropriate for these nonfunctional neoplasms. C1 [Blansfield, Joseph A.; Morita, Shane Y.; Pingpank, James F.; Alexander, H. Richard; Seidel, Geoffrey; Shutack, Yvonne; Yuldasheva, Nargiza; Eugeni, Michelle; Bartlett, David L.; Libutti, Steven K.] NCI, Surg Branch, Tumor Angiogenesis Sect, NIH, Bethesda, MD 20892 USA. [Choyke, Lynda; Glenn, Gladys M.; Middelton, Lindsay; Linehan, W. Marston] NCI, NIH, Urol Oncol Branch, Bethesda, MD 20892 USA. [Choyke, Peter L.] NCI, NIH, Mol Imaging Program, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, Tumor Angiogenesis Sect, NIH, 10 Ctr Dr, CRC 4W-5940, Bethesda, MD 20892 USA. EM libuttis@mail.nih.gov NR 11 TC 89 Z9 92 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2007 VL 142 IS 6 BP 814 EP 818 DI 10.1016/j.surg.2007.09.012 PG 5 WC Surgery SC Surgery GA 242QV UT WOS:000251741500006 PM 18063061 ER PT J AU Bryant, BJ Bianchi, M Wesley, RA Stroncek, DF Leitman, SF AF Bryant, Barbara J. Bianchi, Maria Wesley, Robert A. Stroncek, David F. Leitman, Susan F. TI Leukoreduction filtration of whole-blood units from sickle trait donors: effects of a metered citrate anticoagulant system SO TRANSFUSION LA English DT Article ID CELL TRAIT; WBC REDUCTION; POLYMERIZATION; COMPONENTS AB BACKGROUND: Polymerization of hemoglobin (Hb) S is exacerbated by acidic and hyperosmotic citrate anticoagulant solutions and often results in occlusion of leukoreduction filters by red blood cells (RBCs) from sickle cell trait (Hb AS) donors. This study evaluates a blood collection instrument that adds citrate anticoagulant in a metered fashion, thus mitigating adverse citrate effects. STUDY DESIGN AND METHODS: Collection of whole blood by a metered anticoagulant system was compared to traditional phlebotomy in 12 Hb AS and 12 non-sickle trait (Hb AA) donors. Each donated twice; on one occasion, units were filtered after 4-hour storage at 20 to 24 degrees C, and on the other, units were stored at 1 to 6 degrees C for 24 hours before filtration. RESULTS: Filtration times, RBC recoveries, and residual white blood cell (WBC) counts met defined criteria more often in Hb AS units collected by a metered anticoagulant system (9 of 12, 8 of 12, and 4 of 12, respectively) compared to traditional phlebotomy (1 of 12, 2 of 12, and 0 of 12, respectively). Overall, Hb AS units filtered better after storage at 1 to 6 degrees C for 24 hours, with units collected by a metered anticoagulant system undergoing filtration most effectively (5 of 6 had > 85% RBC recovery, 3 of 6 had < 5 x 10(6) residual WBC). Units exhibited similar changes in RBC storage parameters. CONCLUSION: Use of a metered anticoagulation instrument demonstrates potential for successful leukoreduction and acceptable storage of Hb AS units; however, the system needs further modifications and improvements before it can be utilized to collect and leukoreduce Hb AS blood. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Dept Biostat Serv, Bethesda, MD 20892 USA. RP Bryant, BJ (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. EM bryantb2@cc.nih.gov NR 17 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2007 VL 47 IS 12 BP 2233 EP 2241 DI 10.1111/j.1537-2995.2007.01452.x PG 9 WC Hematology SC Hematology GA 235BD UT WOS:000251207600011 PM 17714416 ER PT J AU Klein, HG Anderson, D Bernardi, MJ Cable, R Carey, W Hoch, JS Robitaille, N Sivilotti, MLA Smaill, F AF Klein, Harvey G. Anderson, David Bernardi, Marie-Josee Cable, Ritchard Carey, William Hoch, Jeffrey S. Robitaille, Nancy Sivilotti, Marco L. A. Smaill, Fiona TI Pathogen inactivation: making decisions about new technologies - Report of a consensus conference SO TRANSFUSION LA English DT Editorial Material ID AMERICAN-RED-CROSS; VERSUS-HOST-DISEASE; FRESH-FROZEN PLASMA; TRANSFUSION-TRANSMITTED INFECTIONS; HUMAN-IMMUNODEFICIENCY-VIRUS; COST-EFFECTIVENESS ANALYSIS; CANADIAN BLOOD SERVICES; HEPATITIS-B-VIRUS; ACUTE LUNG INJURY; BACTERIAL-CONTAMINATION C1 NIH, Bethesda, MD USA. QE II Hlth Sci Ctr, Halifax, NS, Canada. CHUM, Montreal, PQ, Canada. American Red Cross Blood Serv, Farmington, CT USA. St Michaels Hosp, Toronto, ON, Canada. CHU St Justine, Quebec City, PQ, Canada. Queens Univ, Kingston, ON K7L 3N6, Canada. McMaster Univ, Fac Hlth Sci, Hamilton, ON L8S 4L8, Canada. RP Klein, HG (reprint author), NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. EM hklein@dtm.cc.nih.gov OI Hoch, Jeffrey/0000-0002-4880-4281 NR 80 TC 71 Z9 73 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2007 VL 47 IS 12 BP 2338 EP 2347 DI 10.1111/j.1537-2995.2007.01512.x PG 10 WC Hematology SC Hematology GA 235BD UT WOS:000251207600024 PM 18036075 ER PT J AU Stehle, IM AF Stehle, Isa M. TI pEPI: a non-viral episomally replicating vector for gene therapy and animal transgenesis SO TRANSGENIC RESEARCH LA English DT Meeting Abstract C1 NIH, Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. Univ Witten Herdecke, Inst Cell Biol, Witten, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD DEC PY 2007 VL 16 IS 6 BP 846 EP 846 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 228IE UT WOS:000250722800029 ER PT J AU Diatchenko, L Nackley, AG Tchivileva, IE Shabalina, SA Maixner, W AF Diatchenko, Luda Nackley, Andrea G. Tchivileva, Inna E. Shabalina, Svetlana A. Maixner, William TI Genetic architecture of human pain perception SO TRENDS IN GENETICS LA English DT Review ID CATECHOL-O-METHYLTRANSFERASE; VULVAR VESTIBULITIS SYNDROME; 5-HT2A RECEPTOR GENE; CONGENITAL INSENSITIVITY; POSSIBLE ASSOCIATION; T102C POLYMORPHISM; HUMAN BRAIN; COMT; EXPRESSION; ANALGESIA AB Pain is emotionally detrimental and consciously avoided; however, it is absolutely crucial for our survival. Pain perception is one of the most complicated measurable traits because it is an aggregate of several phenotypes associated with peripheral and central nervous system dynamics, stress responsiveness and inflammatory state. As a complex trait, it is expected to have a pollygenic nature shaped by environmental pressures. Here we discuss what is known about these contributing genetic variants, including recent discoveries that show a crucial role of voltage-gated sodium channel Nav1.7 in pain perception and how we can advance our understanding of the pain genetic network. We propose how both rare deleterious genetic variants and common genetic polymorphisms are mediators of human pain perception and clinical pain phenotypes. C1 [Diatchenko, Luda; Nackley, Andrea G.; Tchivileva, Inna E.; Maixner, William] Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA. [Shabalina, Svetlana A.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Diatchenko, L (reprint author), Univ N Carolina, Ctr Neurosensory Disorders, 2190 Old Dent Bldg, Chapel Hill, NC 27599 USA. EM lbdiatch@email.une.edu RI Shabalina, Svetlana/N-8939-2013 OI Shabalina, Svetlana/0000-0003-2272-7473 FU Intramural NIH HHS; NIDCR NIH HHS [R01-DE16558, U01-DE017018]; NINDS NIH HHS [P01 NS045685] NR 81 TC 96 Z9 96 U1 3 U2 13 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD DEC PY 2007 VL 23 IS 12 BP 605 EP 613 DI 10.1016/j.tig.2007.09.004 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 247KT UT WOS:000252078500003 PM 18023497 ER PT J AU Corby, PM Bretz, WA Hart, TC Schork, NJ Wessel, J Lyons-Weiler, J Paster, BJ AF Corby, Patricia M. Bretz, Walter A. Hart, Thomas C. Schork, Nicholas J. Wessel, J. Lyons-Weiler, James Paster, Bruce J. TI Heritability of oral microbial species in caries-active and caries-free twins SO TWIN RESEARCH AND HUMAN GENETICS LA English DT Article ID MUTANS STREPTOCOCCI; MOLECULAR ANALYSIS; DENTAL-CARIES; CHILDHOOD CARIES; BACTERIAL-FLORA; ASSOCIATIONS; DECAY; MICE AB Oral microbes that colonize in the mouths of humans contribute to disease susceptibility, but it is unclear if host genetic factors mediate colonization. We therefore tested the hypothesis that the levels at which oral microbes colonize in the mouth are heritable. Dental plaque biofilms were sampled from intact tooth surfaces of 118 caries-free twins. An additional 86 caries-active twins were sampled for plaque from carious lesions and intact tooth surfaces. Using a reverse capture checkerboard assay the relative abundance of 82 bacterial species was determined. An integrative computational predictive model determined microbial abundance patterns of microbial species in caries-free twins as compared to caries-active twins. Heritability estimates were calculated for the relative microbial abundance levels of the microbial species in both groups. The levels of 10 species were significantly different in healthy individuals than in caries-active individuals, including, A. defectiva, S. parasanguinis, S. mitis/oralis, S. sanguinis, S. cristatus, S. salivarius, Streptococcus sp. clone CHO16, G. morbillorum and G. haemolysans. Moderate to high heritability estimates were found for these species (h(2) = 56%-80 %, p < .0001). Similarity of the overall oral microbial flora was also evident in caries-free twins from multivariate distance matrix regression analysis. It appears that genetic and/or familial factors significantly contribute to the colonization of oral beneficial species in twins. C1 [Corby, Patricia M.; Bretz, Walter A.] NYU, Coll Dent, New York, NY 10010 USA. [Schork, Nicholas J.; Wessel, J.] Univ Calif San Diego, Scripps Res Inst, San Diego, CA 92103 USA. [Schork, Nicholas J.; Wessel, J.] Univ Calif San Diego, Ctr Human Genet & Genom, San Diego, CA 92103 USA. [Hart, Thomas C.] NIDCR, NIH, Div Intramural Clin Res, Bethesda, MD USA. [Lyons-Weiler, James] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Paster, Bruce J.] Forsyth Inst, Boston, MA USA. RP Corby, PM (reprint author), NYU, Coll Dent, 345 E 24th St, New York, NY 10010 USA. EM patricia.corby@nyu.edu OI Wessel, Jennifer/0000-0002-7031-0085 FU NHLBI NIH HHS [U01 HL064777, HL/MH065571-02, HL070137-01, HL074730-02, R01 HL070137, R01 HL074730, U01 HL064777-06]; NIA NIH HHS [U19 AG023122, U19 AG023122-01]; NIDCR NIH HHS [DE14528, DE15351, K12 DE014528, R01 DE015351, R01 DE015351-03] NR 31 TC 21 Z9 22 U1 0 U2 6 PU AUSTRALIAN ACAD PRESS PI BOWEN HILLS PA 32 JEAYS ST, BOWEN HILLS, QLD 4006, AUSTRALIA SN 1832-4274 J9 TWIN RES HUM GENET JI Twin Res. Hum. Genet. PD DEC PY 2007 VL 10 IS 6 BP 821 EP 828 DI 10.1375/twin.10.6.821 PG 8 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 242LW UT WOS:000251727600004 PM 18179393 ER PT J AU Hickey, MJ Held, KS Baum, E Gao, JL Murphy, PM Lane, TE AF Hickey, Michelle J. Held, Katherine S. Baum, Elizabeth Gao, Ji-Liang Murphy, Philip M. Lane, Thomas E. TI CCR1 deficiency increases susceptibility to fatal coronavirus infection of the central nervous system SO VIRAL IMMUNOLOGY LA English DT Article ID MOUSE HEPATITIS-VIRUS; INDUCED DEMYELINATING DISEASE; CHEMOKINE RECEPTOR CCR5; CD4(+) T-CELLS; HOST-DEFENSE; NEUROTROPIC CORONAVIRUS; MACROPHAGE INFILTRATION; FUNCTIONAL EXPRESSION; INDUCIBLE PROTEIN-10; MULTIPLE-SCLEROSIS AB The role of CC chemokine receptor 1 (CCR1) in host defense and disease development was determined in a model of viral-induced neurologic disease. Intracerebral (IC) infection of mice with mouse hepatitis virus (MHV) results in an acute encephalitis followed by a chronic demyelinating disease similar in pathology to the disease multiple sclerosis (MS). No increase in mortality was observed during the acute phase of disease following MHV infection of mice lacking CCR1 (CCR1(-/-)) as compared to wild-type (CCR1(+/+)) mice. However, by 21 d post-infection, 74% of CCR1(-/-) mice had succumbed to death compared to only 32% mortality of CCR1(+/+) mice, indicating that chemokine signaling through CCRl significantly (p <= 0.04) enhanced survival following IC infection with MHV. Increased mortality in CCR1(-/-) mice was not associated with increased viral recovery from the CNS, although CCRl deficiency correlated with reduced T-cell accumulation within the CNS during acute, but not chronic, disease. Despite the reduction in T-cell trafficking into the CNS of CCR1(-/-) mice during acute disease, components of host defense remained unaltered; T-cell effector functions including cytolytic activity and proliferation and the expression of IFN-gamma within the CNS were not significantly different between CCR1(+/+) and CCR1(-/-) infected mice. In addition, macrophage infiltration into the CNS was unaffected in MHV-infected CCR1(-/-) mice when compared to CCR1(+/+) mice. Furthermore, assessment of neuropathology revealed no difference in the severity of demyelination between CCRl-deficient and wild-type mice. Together, these findings reveal that T-cell and macrophage trafficking are not dependent on CCRl and highlight an important role for CCRl signaling in promoting survival during chronic MHV infection. C1 [Hickey, Michelle J.; Held, Katherine S.; Baum, Elizabeth; Lane, Thomas E.] Univ Calif Irvine, Dept Mol Biol & Biochem, Ctr Immunol, Irvine, CA 92697 USA. [Gao, Ji-Liang; Murphy, Philip M.] NIAID, Natl Inst Hlth, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Lane, TE (reprint author), Univ Calif Irvine, Dept Mol Biol & Biochem, Ctr Immunol, 3205 McGaugh Hall, Irvine, CA 92697 USA. EM tlane@uci.edu FU NINDS NIH HHS [NS018146, NS041249] NR 38 TC 5 Z9 5 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PD DEC PY 2007 VL 20 IS 4 BP 599 EP 608 DI 10.1089/vim.2007.0056 PG 10 WC Immunology; Virology SC Immunology; Virology GA 246RL UT WOS:000252024600010 PM 18158733 ER PT J AU Amexis, G Young, NS AF Amexis, Georgios Young, Neal S. TI Multiple antigenic peptides as vaccine platform for the induction of humoral responses against dengue-2 virus SO VIRAL IMMUNOLOGY LA English DT Article ID T-CELL EPITOPES; E-GLYCOPROTEIN; ENVELOPE GLYCOPROTEIN; NEUTRALIZING EPITOPE; RHESUS MACAQUES; A VIRUS; PROTEIN; ANTIBODIES; PREDICTION; SEROTYPES AB Dengue is an important agent of human disease for which no licensed vaccine is available to the public. We used multiple antigenic peptides (MAPS) as an antigen carrier for the development of subunit vaccines against dengue-2 virus (DEN-2). Commercially available software (MacVector (TM) 7.0) was used to identify potential antigenic B-cell epitopes of E-glycoprotein. A total of 60 BALB/c mice were immunized with 12 recombinant DEN-2-specific MAPS and the humoral immune response was assessed by anti-DEN-2 ELISA and PRNT50 assays. Anti-DEN-2 ELISA showed high levels of anti-DEN-2 antibodies and post-immune sera reduced viral infectivity and prevented infection of monkey kidney cells (LLC-MK2) with live DEN-2 virus. Seven neutralizing DEN-2 epitopes were identified that generated PRNT50 titers of up to 1:160. Our findings show that the MAP platform can be used as an antigen-presenting platform for dengue vaccine development. C1 [Amexis, Georgios; Young, Neal S.] NHLBI, Natl Inst Hlth, Hematol Branch, Bethesda, MD 20892 USA. RP Amexis, G (reprint author), NHLBI, Natl Inst Hlth, Hematol Branch, Bldg 10,Room 3-5256,9000 Rockville Pike, Bethesda, MD 20892 USA. EM amexis@nih.gov NR 41 TC 18 Z9 24 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PD DEC PY 2007 VL 20 IS 4 BP 657 EP 663 DI 10.1089/vim.2007.0029 PG 7 WC Immunology; Virology SC Immunology; Virology GA 246RL UT WOS:000252024600015 PM 18158738 ER PT J AU Kerin, TK Kane, EM Glass, R Gentsch, JR AF Kerin, Tara K. Kane, Erin M. Glass, Roger Gentsch, Jon R. TI Characterization of VP6 genes from rotavirus strains collected in the United States from 1996-2002 SO VIRUS GENES LA English DT Article DE rotavirus; VP6 ID POLYMERASE CHAIN-REACTION; GROUP-A ROTAVIRUSES; REVERSE TRANSCRIPTION-PCR; MONOCLONAL-ANTIBODIES; SEQUENCE-ANALYSIS; STOOL SPECIMENS; GASTROENTERITIS; CHILDREN; IDENTIFICATION; SUBSTITUTIONS AB We sequenced 22 VP6 genes from common rotavirus strains P[81, G1; P[4], G2; P[8], G3; P[8], G4 and P[8], G9 and uncommon type P[6], G9 collected in the US over a 6-year period. All strains defined as members of VP6 antigenic subgroup (SG) I according to reactivity patterns with monoclonal antibodies formed a genetic cluster (Genogroup I) with SG I reference strains. Similarly, all strains in antigenic SGII formed a group (Genogroup 11) with corresponding standard strains of the same SG. Most US strains of each genogroup had diverged by 10-15% from the VP6 gene sequence of reference strains collected >20 years earlier and some recent isolates from other countries. Evolutionary analysis demonstrated that recently isolated US strains of both genogroups have diverged into 2-3 related clusters consistent with other recent findings. Unexpectedly, some recent isolates from other countries have diverged greatly from both older reference isolates and from the recent US isolates characterized here. This finding suggests that genetic diversity in human rotavirus VP6 genes may be greater than previously recognized. These sequences will help in the construction of a VP6 gene database to aid in the development of broadly reactive molecular assays and permit identification of regions where primers and probes for existing assays may need to be redesigned. C1 Ctr Dis Control & Prevent, Natl Ctr Immunizat & Res Dis, Coordinat Ctr Infect Dis, Div Viral Dis Gastroenter & Res Viruses Lab Branc, Atlanta, GA 30333 USA. NIH, Forgart Int Ctr, Bethesda, MD 20892 USA. RP Gentsch, JR (reprint author), Ctr Dis Control & Prevent, Natl Ctr Immunizat & Res Dis, Coordinat Ctr Infect Dis, Div Viral Dis Gastroenter & Res Viruses Lab Branc, 1600 Clifton RD,NE MS G04, Atlanta, GA 30333 USA. EM jrg4@cdc.gov NR 37 TC 21 Z9 22 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PD DEC PY 2007 VL 35 IS 3 BP 489 EP 495 DI 10.1007/s11262-007-0119-7 PG 7 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA 232ZM UT WOS:000251060200003 PM 17564821 ER PT J AU McComsey, GA Kendall, MA Tebas, P Swindells, S Hogg, E Alston-Smith, B Suckow, C Gopalakrishnan, G Benson, C Wohl, DA AF McComsey, Grace A. Kendall, Michelle A. Tebas, Pablo Swindells, Susan Hogg, Evelyn Alston-Smith, Beverly Suckow, Carol Gopalakrishnan, Geetha Benson, Constance Wohl, David A. TI Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV SO AIDS LA English DT Article DE alendronate; bisphosphonates; bone markers; decreased bone mineral density; osteopenia; osteoporosis ID ANTIRETROVIRAL THERAPY; RANDOMIZED-TRIAL; FRACTURE RISK; POSTMENOPAUSAL OSTEOPOROSIS; BIOCHEMICAL MARKERS; VERTEBRAL FRACTURE; WOMEN; OSTEOPENIA/OSTEOPOROSIS; INFECTION; MEN AB Background: Decreased bone mineral density (BMD) is prevalent in HIV-infected patients. Bisphosphonates are currently the mainstay of treatment for postmenopausal and male osteoporosis in HIV-uninfected individuals; however, their efficacy and safety in HIV-infected patients remains unclear. Methods: In this prospective, randomized, placebo-controlled multicenter trial, we studied the effectiveness of calcium and vitamin D supplementation with or without alendronate in improving BMD in HIV-infected subjects receiving stable antiretroviral therapy. Subjects with secondary causes of osteoporosis were excluded. The study was powered to detect differences of 3.5% between arms and to detect a moderate sex effect in percentage change in lumbar spine BMD. All dual-energy X-ray absorptiometry scans were analysed centrally, blinded by arm. Results: The 82 subjects enrolled were 71% men, 77% white, with a baseline median age of 48 years, CD4 cell count of 469 cells/mu l, and lumbar spine t-score of less than 2.1; 91 had HIV-RNA levels less than 400 copies/ml, and 99% were taking antiretroviral drugs. Compared with calcium/vitamin D alone, alendronate plus calcium/vitamin D resulted in significant improvements in BMD at the lumbar spine, total hip, and trochanter, but not at the femoral neck, compared with baseline. There were trends towards significant increases in BMD values in the calcium/vitamin D group at the lumbar spine, total hip, and femoral neck. There were no apparent sex differences in the responses to therapy. Alendronate was well tolerated, without significant adverse events. Conclusion: Once-weekly alendronate is safe and effective in the treatment of decreased BMD in HIV-infected patients. (C) 2007 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [McComsey, Grace A.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [Kendall, Michelle A.] Harvard Univ, Harvard Sch Publ Hlth, Stat & Data Management Ctr, Boston, MA USA. [Tebas, Pablo] Univ Penn, Philadelphia, PA 19104 USA. [Swindells, Susan] Univ Nebraska Med Ctr, Omaha, NE USA. [Hogg, Evelyn] Social Sci Syst, Silver Spring, MD USA. [Alston-Smith, Beverly] NIH, Natl Inst Allergy & Infect Dis, Bethesda, MD USA. [Suckow, Carol] Frontier Sci Technol & Res Fdn, Amherst, NY USA. Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Benson, Constance] Univ Calif San Diego, San Diego, CA 92103 USA. [Wohl, David A.] Univ N Carolina, Chapel Hill, NC USA. RP McComsey, GA (reprint author), Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM gam9@case.edu RI Tebas, Pablo/A-7061-2008; Kendall, Michelle/B-7665-2016 OI Kendall, Michelle/0000-0001-9160-4544 FU NCRR NIH HHS [MO1 RR00044, MO1 RR00047, MO1-RR00096, RR00046]; NIAID NIH HHS [AI25868, 01AI046383, 5 UO1 AI027666, 5-P30-AI-045008-07, AI -27665, AI 25915, AI 27664, AI025879, AI25903, AI27658, AI27670, AI46339, AI46386, AI50410, UO1 AI025924, UO1 AI38558, UO1 AI38855, UO1AI32782, UOI-AI 032783-13] NR 27 TC 82 Z9 86 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 30 PY 2007 VL 21 IS 18 BP 2473 EP 2482 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 241DF UT WOS:000251636400013 PM 18025884 ER PT J AU Thiessen, C Ssekubugu, R Wagman, J Kiddugavu, M Wawer, MJ Emanuel, E Gray, R Serwadda, D Grady, C AF Thiessen, Carrie Ssekubugu, Robert Wagman, Jennifer Kiddugavu, Mohammed Wawer, Maria J. Emanuel, Ezekiel Gray, Ronald Serwadda, David Grady, Christine TI Personal and community benefits and harms of research: views from Rakai, Uganda SO AIDS LA English DT Article DE clinical trials; ethics; human experimentation; research; risks and benefits ID PROTECTING COMMUNITIES; CARE RESPONSIBILITIES; MEDICAL RESEARCHERS; AIDS-PREVENTION; CLINICAL CARE; DETERMINANTS; COUNTRIES; WEALTH; TRIAL AB Objectives: To assess what individuals in low-income countries perceive as benefits and harms of population-based HIV/STD research. Design: A total of 811 research participants, research decliners, and community opinion leaders in the Rakai District, Uganda were surveyed. Types of personal and community benefits and harms, as well as rates of reporting great personal and community benefit were assessed. Methods: Using logistic regression, demographic characteristics, participant and opinion leader status, use of Rakai Health Sciences Program (RHSP) services, and perceived research effects were entered as predictors of reported great personal and great community benefit. Results: Most respondents thought that RHSP research was of great personal (85%) and community (88%) benefit. The perception that the RHSP was a great personal benefit was correlated with female sex, post-secondary education, frequent use of RHSP-sponsored medical services, health knowledge gains, and increased hope for future health improvements. Persons of non-Baganda ethnicity and 30-39 year-olds were less likely to believe research was personally beneficial. Regarding research as a great community benefit was associated with reported health knowledge gains, greater hope for Rakai residents' future health, and local economic benefit. Decliners were the most likely to report a personal harm, while community opinion leaders identified community harms at the highest rates. Conclusions: The majority of Rakai residents report that HIV/STD research has enhanced their own and their communities' welfare. Different factors were associated with the belief that research is a personal versus community benefit. Variations in participant, decliner, and community opinion leader perceptions highlight inadequacies of current community consultation mechanisms. (C) 2007 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Thiessen, Carrie; Emanuel, Ezekiel; Grady, Christine] NIH, Dept Clin Bioeth, Sect Human Subject Res, Bethesda, MD 20892 USA. [Ssekubugu, Robert; Wagman, Jennifer; Kiddugavu, Mohammed] Uganda Virus Res Inst, Rakai Hlth Sci Program, Entebbe, Uganda. [Wawer, Maria J.] Johns Hopkins Bloomberg Sch Publ Hlth, Populat & Family Hlth Sci, Baltimore, MD USA. [Serwadda, David] Makerere Univ, Inst Publ Hlth, Kampala, Uganda. RP Grady, C (reprint author), NIH, Dept Clin Bioeth, Sect Human Subject Res, Bldg 10,Rm 1C118, Bethesda, MD 20892 USA. EM cgrady@cc.nih.gov OI Wagman, Jennifer/0000-0002-9957-1932 NR 29 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 30 PY 2007 VL 21 IS 18 BP 2493 EP 2501 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 241DF UT WOS:000251636400015 PM 18025886 ER PT J AU Hadigan, C Mazza, S Crum, D Grinspoon, S AF Hadigan, Colleen Mazza, Sasha Crum, Dana Grinspoon, Steven TI Rosiglitazone increases small dense low-density lipoprotein concentration and decreases high-density lipoprotein particle size in HIV-infected patients SO AIDS LA English DT Article ID DOUBLE-BLIND; ANTIRETROVIRAL THERAPY; RANDOMIZED-TRIAL; RISK-FACTORS; LIPODYSTROPHY; PIOGLITAZONE; RESISTANCE; METFORMIN; DISEASE; TYPE-2 AB After 12 weeks of rosiglitazone treatment, significant increases in total and small dense low-density lipoprotein, and the total: high-density lipoprotein (HDL)-cholesterol ratio were found. The large HDL concentration and HDL particle size decreased significantly with rosiglitazone compared with placebo. These data indicate the production of a more atherogenic lipid profile with rosiglitazone, a consideration when selecting treatment for the growing population of HIV-infected patients with type 2 diabetes and dyslipidemia. C1 [Hadigan, Colleen; Crum, Dana] NIH, Natl Inst All & Infect Dis, Lab Immunoregulat, Bethesda, MD 20892 USA. [Mazza, Sasha; Grinspoon, Steven] Harvard Univ, Harvard Med Sch, Program Nutr Met, Boston, MA 02115 USA. RP Hadigan, C (reprint author), NIH, Natl Inst All & Infect Dis, Lab Immunoregulat, Bldg 10, Bethesda, MD 20892 USA. FU NCRR NIH HHS [M01 RR002635, M01 RR000088, MO1 RR 02635, MO1 RR 300088]; NIDDK NIH HHS [R01 DK059535, P30 DK040561-12, K23 DK002844, P30 DK040561, R01 DK 59535, K23 DK 20844] NR 20 TC 10 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 30 PY 2007 VL 21 IS 18 BP 2543 EP 2546 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 241DF UT WOS:000251636400025 PM 18025896 ER PT J AU Barski, A Cuddapah, S Cui, KR Roh, TY Schones, DE Wang, ZB Wei, G Chepelev, I Zhao, KJ AF Barski, Artem Cuddapah, Suresh Cui, Kairong Roh, Tae-Young Schones, Dustin E. Wang, Zhibin Wei, Gang Chepelev, Iouri Zhao, Keji TI Response: Mapping nucleosome positions using ChIP-Seq data SO CELL LA English DT Letter ID PROMOTER; GENOME C1 [Barski, Artem; Cuddapah, Suresh; Cui, Kairong; Roh, Tae-Young; Schones, Dustin E.; Wang, Zhibin; Wei, Gang; Zhao, Keji] NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. [Chepelev, Iouri] Univ Calif Los Angeles, Gonda Neurosci & Genet Res Ctr, Dept Human Genet, Los Angeles, CA 90095 USA. RP Zhao, KJ (reprint author), NHLBI, Lab Mol Immunol, Bldg 10, Bethesda, MD 20892 USA. EM zhaok@nhlbi.nih.gov OI Barski, Artem/0000-0002-1861-5316 NR 4 TC 5 Z9 5 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 30 PY 2007 VL 131 IS 5 BP 832 EP 833 DI 10.1016/j.cell.2007.11.018 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 243MG UT WOS:000251800900002 ER PT J AU Wan, FY Anderson, DE Barnitz, RA Snow, A Bidere, N Zheng, LX Hegde, V Lam, LT Staudt, LM Levens, D Deutsch, WA Lenardo, MJ AF Wan, Fengyi Anderson, D. Eric Barnitz, Robert A. Snow, Andrew Bidere, Nicolas Zheng, Lixin Hegde, Vijay Lam, Lloyd T. Staudt, Louis M. Levens, David Deutsch, Walter A. Lenardo, Michael J. TI Ribosomal protein S3: A KH domain subunit in NF-kappa B complexes that mediates selective gene regulation SO CELL LA English DT Article ID RIBOSOMAL-PROTEIN S3; NUCLEAR RIBONUCLEOPROTEIN-K; TRANSCRIPTION FACTOR; GENOTOXIC STRESS; BINDING SITES; DNA-BINDING; HUMAN-CELLS; INDUCTION; ACTIVATION; MECHANISM AB NF-kappa B is a DNA-binding protein complex that transduces a variety of activating signals from the cytoplasm to specific sets of target genes. To understand the preferential recruitment of NF-kappa B to specific gene regulatory sites, we used NF-kappa B p65 in a tandem affinity purification and mass spectrometry proteomic screen. We identified ribosomal protein S3 (RPS3), a KH domain protein, as a non-Rel subunit of p65 homodimer and p65-p50 heterodimer DNA-binding complexes that synergistically enhances DNA binding. RPS3 knockdown impaired NF-kappa B-mediated transcription of selected p65 target genes but not nuclear shuttling or global protein translation. Rather, lymphocyte-activating stimuli caused nuclear translocation of RPS3, parallel to p65, to form part of NF-kappa B bound to specific regulatory sites in chromatin. Thus, RPS3 is an essential but previously unknown subunit of NF-kappa B involved in the regulation of key genes in rapid cellular activation responses. Our observations provide insight into how NF-kappa B selectively controls gene expression. C1 [Wan, Fengyi; Barnitz, Robert A.; Snow, Andrew; Bidere, Nicolas; Zheng, Lixin; Lenardo, Michael J.] NIAID, Immunol Lab, Bethesda, MD 20892 USA. [Anderson, D. Eric] Natl Inst Diabet & Digesti & Kidney Dis, Prot & Mass Spectrometry Facil, Bethesda, MD 20892 USA. [Lam, Lloyd T.; Staudt, Louis M.] Ctr Canc Res, Natl Canc Inst, Metabolism Branch, Bethesda, MD 20892 USA. [Levens, David] Ctr Canc Res, Natl Canc Inst, Pathol Lab, Bethesda, MD 20892 USA. [Hegde, Vijay; Deutsch, Walter A.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, Bethesda, MD 20892 USA. EM lenardo@nih.gov RI Levens, David/C-9216-2009; bidere, nicolas/K-8887-2015; OI Levens, David/0000-0002-7616-922X; bidere, nicolas/0000-0001-9177-0008; Barnitz, Tony/0000-0002-9634-4558 FU Intramural NIH HHS; NCI NIH HHS [CA 109798] NR 34 TC 164 Z9 177 U1 2 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 30 PY 2007 VL 131 IS 5 BP 927 EP 939 DI 10.1016/j.cell.2007.10.009 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 243MG UT WOS:000251800900015 PM 18045535 ER PT J AU Nguyen, MQ Zhou, ZS Marks, CA Ryba, NJP Belluscio, L AF Nguyen, Minh Q. Zhou, Zhishang Marks, Carolyn A. Ryba, Nicholas J. P. Belluscio, Leonardo TI Prominent roles for odorant receptor coding sequences in allelic exclusion SO CELL LA English DT Article ID OLFACTORY MARKER PROTEIN; MOLECULAR-CLONING; TOPOGRAPHIC MAP; AXON GUIDANCE; SENSORY MAP; EXPRESSION; MOUSE; BULB; NEURONS; SYSTEM AB Mammalian odorant receptors (ORs) are crucial for establishing the functional organization of the olfactory system, but the mechanisms controlling their expression remain largely unexplained. Here, we utilized a transgenic approach to explore OR gene regulation. We determined that although olfactory sensory neurons (OSNs) are capable of supporting expression of multiple functional ORs, several levels of control ensure that each neuron normally expresses only a single odorant receptor. Surprisingly, this regulation extends beyond endogenous ORs even preventing expression of transgenes consisting of OR-coding sequences driven by synthetic promoters. Thus, part of the intrinsic feedback system must rely on elements present in the OR-coding sequence. Notably, by expressing the same transgenic ORs precociously in immature neurons, we have overcome this suppression and established a generic method to express any OR in similar to 90% of OSNs. These results provide important insights into the hierarchy of OR gene expression and the vital role of the OR-coding sequence in this regulation. C1 [Nguyen, Minh Q.; Ryba, Nicholas J. P.] Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. [Zhou, Zhishang; Marks, Carolyn A.; Belluscio, Leonardo] NIH, NINDS, Bethesda, MD 20892 USA. RP Ryba, NJP (reprint author), Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. EM nick.ryba@nih.gov FU Intramural NIH HHS [Z01 DE000561-15, Z01 NS003002-05] NR 40 TC 83 Z9 86 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 30 PY 2007 VL 131 IS 5 BP 1009 EP 1017 DI 10.1016/j.cell.2007.10.050 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 243MG UT WOS:000251800900021 PM 18045541 ER PT J AU Wei, L Laurence, A Elias, KM O'Shea, JJ AF Wei, Lai Laurence, Arian Elias, Kevin M. O'Shea, John J. TI IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELLS; GENE-EXPRESSION; RECEPTOR; DIFFERENTIATION; CYTOKINE; INTERLEUKIN-21; INFLAMMATION; INTERFERON; ACTIVATION; MECHANISMS AB CD4(+) helper T cells can differentiate into several possible fates including: Th1, Th2, T regulatory, and Th17 cells. Although, cytokine production by non-T cells is an important factor in helper T cell differentiation, a characteristic feature of both Th1 and Th2 lineages is their ability to secrete cytokines that promote their respective differentiation. However, cytokines produced by T cells that help to sustain Th17 cells have not yet been identified. Here we show that IL-21 is a product of Th17 cells, which is induced in a Stat3-dependent manner. Additionally, Stat3 can directly bind the Il21 promoter. IL-21 also induces IL-17 production and expression of the transcription factor, ROR gamma t. Furthermore, generation of Th17 cells in the conventional manner is attenuated by blocking IL-21. IL-21 is known to activate Stat3 and its ability to induce Th17 differentiation is abrogated in the absence of Stat3. These data argue that IL-21 serves as an autocrine factor secreted by Th17 cells that promotes or sustains Th17 lineage commitment. C1 NIH, NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA. RP Wei, L (reprint author), NIH, NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. EM weil2@mail.nih.gov RI Laurence, Arian/A-8770-2009; Wei, Lai/D-1088-2014; OI Laurence, Arian/0000-0003-0942-8292; Elias, Kevin/0000-0003-1502-5553 FU Intramural NIH HHS [Z01 AR041106-13] NR 28 TC 328 Z9 350 U1 2 U2 14 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 NOV 30 PY 2007 VL 282 IS 48 BP 34605 EP 34610 DI 10.1074/jbc.M705100200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 234IR UT WOS:000251155200002 PM 17884812 ER PT J AU Basile, JR Gavard, J Gutkind, JS AF Basile, John R. Gavard, Julie Gutkind, J. Silvio TI Plexin-B1 utilizes RhoA and Rho kinase to promote the integrin-dependent activation of Akt and ERK and endothelial cell motility SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; HETEROTRIMERIC G-PROTEINS; LEUKEMIA-ASSOCIATED RHO; FOCAL ADHESION KINASE; PDZ-RHOGEF; RECEPTOR PLEXIN-B1; AXON GUIDANCE; R-RAS; SEMAPHORIN; MECHANISM AB The semaphorins are a family of proteins originally identified as axon-guiding molecules in the developing nervous system that have been recently shown to regulate many cellular functions, including motility, in a variety of cell types. We have previously shown that in endothelial cells Semaphorin 4D acts through its receptor, Plexin-B1, to elicit a pro-angiogenic phenotype that involves the activation of the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. Here we show through the use of a receptor chimeric approach, Plexin-B1 mutants, and dominant negative and pharmacological inhibitors that this response is dependent upon the activation of RhoA and its downstream target, Rho kinase (ROK). Indeed, we demonstrate that in endothelial cells, Semaphorin 4D promotes the formation of focal adhesion complexes, stress fibers, and the phosphorylation of myosin light chain, a response that was abolished by the use of ROK inhibitors and absent from cells expressing Plexin-B1 mutant constructs incapable of signaling to RhoA. Stress fiber polymerization and contraction are in turn necessary for RhoA-dependent pro-angiogenic signaling through Plexin-B1. Furthermore, we observed that in endothelial cells Plexin-B1 promotes the integrin-mediated activation of Pyk2, resulting in the stimulation of PI3K, Akt, and ERK. These findings provide evidence that Plexin-B1 promotes endothelial cell motility through RhoA and ROK by regulating the integrin-dependent signaling networks that result in the activation of PI3K and Akt. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Rm 211, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Gavard, Julie/I-5487-2012 OI Gavard, Julie/0000-0002-7985-9007 NR 54 TC 69 Z9 73 U1 0 U2 12 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 NOV 30 PY 2007 VL 282 IS 48 BP 34888 EP 34895 DI 10.1074/jbc.M705467200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 234IR UT WOS:000251155200031 PM 17855350 ER PT J AU Li, JL Wei, H Chesley, A Moon, C Krawczyk, M Volkova, M Ziman, B Margulies, KB Talan, M Crow, MT Boheler, KR AF Li, Jinliang Wei, Hong Chesley, Alan Moon, Chanil Krawczyk, Melissa Volkova, Maria Ziman, Bruce Margulies, Kenneth B. Talan, Mark Crow, Michael T. Boheler, Kenneth R. TI The pro-angiogenic cytokine pleiotrophin potentiates cardiomyocyte apoptosis through inhibition of endogenous AKT/PKB activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-ASSOCIATED MOLECULE; ANAPLASTIC LYMPHOMA KINASE; GENE-EXPRESSION; PROTEIN-KINASE; BREAST-CANCER; IN-VITRO; HB-GAM; BINDING; RECEPTOR; CELLS AB Pleiotrophin is a development-regulated cytokine and growth factor that can promote angiogenesis, cell proliferation, or differentiation, and it has been reported to have neovasculogenic effects in damaged heart. Developmentally, it is prominently expressed in fetal and neonatal hearts, but it is minimally expressed in normal adult heart. Conversely, we show in a rat model of myocardial infarction and in human dilated cardiomyopathy that pleiotrophin is markedly up-regulated. To elucidate the effects of pleiotrophin on cardiac contractile cells, we employed primary cultures of rat neonatal and adult cardiomyocytes. We show that pleiotrophin is released from cardiomyocytes in vitro in response to hypoxia and that the addition of recombinant pleiotrophin promotes caspase-mediated genomic DNA fragmentation in a dose-and time-dependent manner. Functionally, it potentiates the apoptotic response of neonatal cardiomyocytes to hypoxic stress and to ultraviolet irradiation and of adult cardiomyocytes to hypoxia-reoxygenation. Moreover, UV-induced apoptosis in neonatal cardiomyocytes can be partially inhibited by small interfering RNA-mediated knockdown of endogenous pleiotrophin. Mechanistically, pleiotrophin antagonizes IGF-1 associated Ser-473 phosphorylation of AKT/PKB, and it concomitantly decreases both BAD and GSK3 beta phosphorylation. Adenoviral expression of constitutively active AKT and lithium chloride-mediated inhibition of GSK3 beta reduce the potentiated programmed cell death elicited by pleiotrophin. These latter data indicate that pleiotrophin potentiates cardiomyocyte cell death, at least partially, through inhibition of AKT signaling. In conclusion, we have uncovered a novel function for pleiotrophin on heart cells following injury. It fosters cardiomyocyte programmed cell death in response to pro-apoptotic stress, which may be critical to myocardial injury repair. C1 NIA, NIH, GRC LCS, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Boheler, KR (reprint author), NIA, NIH, GRC LCS, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bohelerk@grc.nia.nih.gov FU NHLBI NIH HHS [HL-073935]; NIA NIH HHS [R01-AG017022] NR 43 TC 20 Z9 21 U1 4 U2 10 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 NOV 30 PY 2007 VL 282 IS 48 BP 34984 EP 34993 DI 10.1074/jbc.M703513200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 234IR UT WOS:000251155200043 PM 17925408 ER PT J AU Mans, J Natarajan, K Balbo, A Schuck, P Eikel, D Hess, S Robinson, H Simic, H Jonjic, S Tiemessen, CT Margulies, DH AF Mans, Janet Natarajan, Kannan Balbo, Andrea Schuck, Peter Eikel, Daniel Hess, Sonja Robinson, Howard Simic, Hrvoje Jonjic, Stipan Tiemessen, Caroline T. Margulies, David H. TI Cellular expression and crystal structure of the murine cytomegalovirus major histocompatibility complex class I-like glycoprotein, m153 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COMPLETE DNA-SEQUENCE; NATURAL-KILLER-CELLS; MOUSE CYTOMEGALOVIRUS; IMMUNOGLOBULIN SUPERFAMILY; IMMUNE EVASION; MOLECULES; RECEPTOR; LIGAND; ACTIVATION; HOMOLOG AB Mouse cytomegalovirus (MCMV), a beta-herpesvirus that establishes latent and persistent infections in mice, is a valuable model for studying complex virus-host interactions. MCMV encodes the m145 family of putative immunoevasins with predicted major histocompatibility complex, class I (MHC-I) structure. Functions attributed to some family members include down-regulation of host MHC-I (m152) and NKG2D ligands (m145, m152, and m155) and interaction with inhibitory or activating NK receptors (m157). We present the cellular, biochemical, and structural characterization of m153, which is a heavily glycosylated homodimer, that does not require beta 2m or peptide and is expressed at the surface of MCMV-infected cells. Its 2.4-angstrom crystal structure confirms that this compact molecule preserves an MHC-I-like fold and reveals a novel mode of dimerization, confirmed by site-directed mutagenesis, and a distinctive disulfide-stabilized extended N terminus. The structure provides a useful framework for comparative analysis of the divergent members of the m145 family. C1 NIAID, Immunol Lab, Mol Biol Sect, Bethesda, MD 20892 USA. NIH, Off Director, Bethesda, MD 20892 USA. Prod Appl Lab, Ithaca, NY 14850 USA. CALTECH, Beckman Inst, Proteome Explorat Lab, Pasadena, CA 91125 USA. Brookhaven Natl Lab, Upton, NY 11973 USA. Univ Rijeka, Dept Histol & Embryol, Fac Med, Rijeka 51000, Croatia. Univ Witwatersrand, Dept Virol, ZA-2050 Johannesburg, South Africa. Natl Inst Communicable Dis, ZA-2131 Johannesburg, South Africa. RP Margulies, DH (reprint author), NIAID, Immunol Lab, Mol Biol Sect, 10 Ctr Dr, Bethesda, MD 20892 USA. EM dhm@nih.gov RI Margulies, David/H-7089-2013; Hess, Sonja/K-4842-2013; OI Hess, Sonja/0000-0002-5904-9816; Schuck, Peter/0000-0002-8859-6966; Margulies, David/0000-0001-8530-7375; Mans, Janet/0000-0001-6721-1177 FU Intramural NIH HHS [Z01 AI000622-16]; Wellcome Trust [, 076352] NR 49 TC 15 Z9 15 U1 0 U2 2 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 NOV 30 PY 2007 VL 282 IS 48 BP 35247 EP 35258 DI 10.1074/jbc.M706782200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 234IR UT WOS:000251155200069 PM 17897947 ER PT J AU Hassoun, AT Erdelyi, F Szabo, G Davis, MI AF Hassoun, Amani T. Erdelyi, Ferenc Szabo, Gabor Davis, Margaret I. TI A rapid screening method for population-specific neuronal motogens, substrates and associated signaling pathways SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE migration; Boyden chamber; brain-derived neurotrophic factor; NT4; cerebellum; TrkB; interneurons; green fluorescent protein ID CEREBELLAR GRANULE NEURONS; ACTIVATED PROTEIN-KINASE; CELL-MIGRATION; TYROSINE PHOSPHORYLATION; MESSENGER-RNA; ADHESION; GROWTH; PROLIFERATION; BRAIN; INHIBITION AB We developed and characterized an assay that allows for rapid examination of migration of specific neuronal populations within a mixed population using the Boyden chamber principle. Migration of cerebellar interneurons and granule cells was examined using mice expressing enhanced green fluorescent protein (eGFP) under the glutamate decarboxylase (GAD(65)) and growth-associated protein-43 (GAP43) promoters, respectively. Brain-derived neurotrophic factor (BDNF) was used as the prototypic motogen for both populations. Fluorescent light-blocking inserts (FluoroBlok (TM)) with different pore sizes and densities were compared in a two-compartment assay. Immunodetection of polarity markers and nuclear staining indicated that dendrites and somata are preferentially extended through the pores in response to BDNF. Inserts coated with extracellular matrix (ECM) proteins were used to examine interactions between BDNF and the ECM during migration. ECM proteins alone stimulated migration when the lower side of the insert was coated, however coating of both sides of the insert slowed migration when compared to poly-D-lysine. Addition of a PI 3-kinase inhibitor to the lower compartment blocked BDNF-stimulated migration of both populations while a Src inhibitor reduced laminin-stimulated migration of interneurons, but not granule cells. We also examined use of neurons cultured from GAD(65)-eGFP mice as a reporter system for promoter activity. GAD(65)-eGFP mice may also be useful as a model for promoter regulation and the potential confounding effects of eGFP induction by the stimuli are also addressed. This assay allows for rapid analysis of motogens, substrates and signaling pathways that regulate migration of selected neuronal populations. (c) 2007 Elsevier B.V All rights reserved. C1 NIAAA, Lab Integrat Neurosci, Sect Synapt Pharmacol, NIH, Bethesda, MD 20892 USA. Hungarian Acad Sci, Inst Expt Med, Dept Gene Technol & Dev Neurobiol, H-1450 Budapest, Hungary. HAS, Inst Expt Med, Transgen Facil, Med Gene Technol Unit, H-1083 Budapest, Hungary. HAS, Inst Expt Med, Lab Mol Biol & Genet, H-1083 Budapest, Hungary. RP Davis, MI (reprint author), NIAAA, Lab Integrat Neurosci, Sect Synapt Pharmacol, NIH, 5625 Fishers Lane,MSC 9411, Bethesda, MD 20892 USA. EM hassouna@mail.nih.gov; erdelyi@koki.hu; szabog@koki.hu; midavis@mail.nih.gov RI Davis, Margaret/F-4165-2010; OI Davis, Margaret/0000-0002-0489-8351 FU Intramural NIH HHS [Z99 AA999999] NR 46 TC 2 Z9 2 U1 0 U2 1 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 NOV 30 PY 2007 VL 166 IS 2 BP 178 EP 194 DI 10.1016/j.jneumeth.2007.07.008 PG 17 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 239AP UT WOS:000251490300003 PM 17826844 ER PT J AU Wang, J Yang, C Wang, E Li, SH Zaveri, N Liu, P AF Wang, Jennie Yang, Chun Wang, Euphemia Li, Shihong Zaveri, Nurulain Liu, Paul TI Chromatographic analysis and decomposition product characterization of compound SR16157 (NSC 732011) SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE SR16157; NSC 732011; forced decomposition; HPLC assay; validation; impurity characterization ID PERFORMANCE LIQUID-CHROMATOGRAPHY; HUMAN-BREAST-CANCER; STEROID SULFATASE; ESTROGEN PRODUCTION; MASS SPECTROMETRY; AROMATASE; METABOLITES; ESTRADIOL; THERAPY; DRUGS AB SR16157 (21-(2-N,N-diethylaminoethyl)oxy-7 alpha-methyl-19-norprena-1,3,5(10)-triene-3-O-sulfamate) is a novel, dual-acting estrone sulfatase inhibitor currently in preclinical development for use in breast cancer therapy. The compound has a dual mechanism of action: the sulfamate-containing parent compound SR16157 inhibits estrogen biosynthesis by irreversibly inhibiting the enzyme estrone sulfatase. The phenolic metabolite, SR16137, generated by the suffatase enzyme is a potent antiestrogen in breast tissues and has beneficial effects in bone and the cardiovascular system. As part of the ongoing preclinical studies, an HPLC assay method has been developed and validated for SR16157. The assay method is specific, accurate (recovery = 99.4-101.1), linear (r(2) >= 0.9999), precise (intraday R.S.D. <= 1.1%, intermediate R.S.D. <= 0.8%), and sensitive (limit of detection = 1.0 1.0 mu g/ml). It separates SR16157 from its impurities and forced decomposition products, which have been characterized by LC coupled with mass and UV spectral data. Major decomposition pathways are hydrolysis, hydroxylation, and oxidation. (c) 2007 Elsevier B.V. All rights reserved. C1 SRI Int, Menlo Pk, CA 94025 USA. NCI, Pharmaceut Resources Branch, DCTD, Bethesda, MD 20892 USA. RP Wang, J (reprint author), SRI Int, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA. EM jennie.wang@sri.com RI Li, Shihong/A-3589-2014 FU NCI NIH HHS [N01-CM-27134, N02-CM-72203] NR 22 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD NOV 30 PY 2007 VL 45 IS 4 BP 572 EP 582 PG 11 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 237VR UT WOS:000251405000005 PM 17913430 ER PT J AU Lengsfeld, BM Rattray, AJ Bhaskara, V Ghirlando, R Paull, TT AF Lengsfeld, Bettina M. Rattray, Alison J. Bhaskara, Venugopal Ghirlando, Rodolfo Paull, Tanya T. TI Sae2 is an endonuclease that processes hairpin DNA cooperatively with the Mre11/Rad50/Xrs2 complex SO MOLECULAR CELL LA English DT Article ID DOUBLE-STRAND BREAKS; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; NUCLEASE ACTIVITY; DAMAGE RESPONSE; REPAIR PROTEINS; RECOMBINATION; YEAST; MRE11; MAINTENANCE AB Mre11/Rad50 complexes in all organisms function in the repair of DNA double-strand breaks. In budding yeast, genetic evidence suggests that the Sae2 protein is essential for the processing of hairpin DNA intermediates and meiotic double-strand breaks by Mre11/Rac50 complexes, but the biochemical basis of this functional relationship is not known. Here we demonstrate that recombinant Sae2 binds DNA and exhibits endonuclease activity on single-stranded DNA independently of Mre11/Rad50 complexes, but hairpin DNA structures are cleaved cooperatively in the presence of Mre11/Rad50 or Mre11/Rad50/Xrs2. Hairpin structures are not processed at the tip by Sae2 but rather at single-stranded DNA regions adjacent to the hairpin. Truncation and missense mutants of Sae2 inactivate this endonuclease activity in vitro and fail to complement Delta sae2 strains in vivo for meiosis and recombination involving hairpin intermediates, suggesting that the catalytic activities of Sae2 are important for its biological functions. C1 Univ Texas Austin, Dept Mol Genet & Microbiol, Austin, TX 78712 USA. Univ Texas, Dept Chem & Biochem, Austin, TX 78712 USA. Univ Texas, Inst Cellular & Mol Biol, Austin, TX 78712 USA. NCI, Frederick Canc Res & Dev Ctr, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. NIH, NIDDK, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Paull, TT (reprint author), Univ Texas Austin, Dept Mol Genet & Microbiol, Austin, TX 78712 USA. EM tpaull@mail.utexas.edu RI Rattray, Alison/A-4847-2008; Ghirlando, Rodolfo/A-8880-2009 FU Intramural NIH HHS; NCI NIH HHS [R01 CA094008, R01 CA094008-06] NR 36 TC 179 Z9 183 U1 0 U2 2 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 NOV 30 PY 2007 VL 28 IS 4 BP 638 EP 651 DI 10.1016/j.molcel.2007.11.001 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 238TK UT WOS:000251470300014 PM 18042458 ER PT J AU Li, P Jiang, S Lee, SL Lin, CY Johnson, MD Dickson, RB Michejda, CJ Roller, PP AF Li, Peng Jiang, Sheng Lee, Sheau-Ling Lin, Cheng Yong Johnson, Michael D. Dickson, Robert B. Michejda, Christopher J. Roller, Peter P. TI Design and synthesis of novel and potent inhibitors of the type II transmembrane serine protease, matriptase, based upon the sunflower trypsin inhibitor-1 SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; BREAST-CANCER CELLS; FACTOR ACTIVATOR INHIBITOR-1; CLINICOPATHOLOGICAL PARAMETERS; RECEPTOR-BINDING; OVARIAN-CANCER; IN-VITRO; EXPRESSION; SEEDS; SFTI-1 AB Matriptase, initially isolated from human breast cancer cells in culture, is a member of the emerging class of type II transmembrane serine proteases. Matriptase blockade could potentially modulate tumorigenesis and metastasis in vivo. Sunflower trypsin inhibitor-1 (1, SFTI-1), isolated from sunflower seeds, exhibits very potent matriptase inhibitory activity. On the basis of these findings, we designed and synthesized 13 analogues of the naturally occurring peptide I with the intention to explore the structure-activity relationships of this type of bicyclic peptides and to improve inhibitory selectivity and metabolic stability of the disulfide-bridge-containing peptide 1. We discovered that the methylenedithioether-bridged compound 14 demonstrates very potent binding affinity to matriptase. Compound 8 exhibits much better selectivity for inhibition of matriptase versus thrombin, whereas compound 2 becomes a more potent thrombin inhibitor, which can be potentially used as an anticoagulant for prophylaxis and therapy of thromboembolism. C1 Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. NIH, NCI, Struct Biophys Lab, Mol Aspects Drug Design Sect, Ft Detrick, MD 21702 USA. NIH, NCI, Med Chem Lab, Ft Detrick, MD 21702 USA. RP Roller, PP (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. EM proll@helix.nih.gov FU Intramural NIH HHS; NCI NIH HHS [R01 CA 096851, R01 CA 104944-01] NR 51 TC 34 Z9 35 U1 0 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 29 PY 2007 VL 50 IS 24 BP 5976 EP 5983 DI 10.1021/jm0704898 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 234RR UT WOS:000251181900014 PM 17985858 ER PT J AU Qiao, CH Gupte, A Boshoff, HI Wilson, DJ Bennett, EM Somu, RV Barry, CE Aldrich, CC AF Qiao, Chunhua Gupte, Amol Boshoff, Helena I. Wilson, Daniel J. Bennett, Eric M. Somu, Ravindranadh V. Barry, Clifton E., III Aldrich, Courtney C. TI 5 '-O-[(N-Acyl)sulfamoyl]adenosines as antitubercular agents that inhibit MbtA: An adenylation enzyme required for siderophore biosynthesis of the mycobactins SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NONRIBOSOMAL PEPTIDE SYNTHETASES; TRANSFER-RNA SYNTHETASES; BACILLUS-ANTHRACIS; IRON; TUBERCULOSIS; ANALOGS; GROWTH; ENTEROBACTIN; ANTIBIOTICS; NUCLEOSIDES AB A study of the structure-activity relationships of 5'-O-[N-(salicyl)sulfamoyl]adenosine (6), a potent inhibitor of the bifunctional enzyme salicyl-AMP ligase (MbtA, encoded by the gene Rv2384) in Mycobacterium tuberculosis, is described, targeting the salicyl moiety. A systematic series of analogues was prepared exploring the importance of substitution at the C-2 position revealing that a hydroxy group is required for optimal activity. Examination of a series of substituted salicyl derivatives indicated that substitution at C-4 was tolerated. Consequently, a series of analogues at this position provided 4-fluoro derivative, which displayed an impressive MIC99 of 0.098 mu M against whole-cell M. tuberculosis under iron-limiting conditions. Examination of other heterocyclic, cycloalkyl, alkyl, and aminoacyl replacements of the salicyl moiety demonstrated that these nonconserative modifications were poorly tolerated, a result consistent with the fairly strict substrate specificities of related non-ribosomal peptide synthetase adenylation enzymes. C1 Univ Minnesota, Ctr Drug Design, Acad Hlth Ctr, Minneapolis, MN 55455 USA. NIAID, TB Res Sect, Bethesda, MD 20892 USA. RP Aldrich, CC (reprint author), Univ Minnesota, Ctr Drug Design, Acad Hlth Ctr, Minneapolis, MN 55455 USA. EM aldri015@umn.edu RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000693-15]; NIAID NIH HHS [R01 AI070219, R01 AI 070219, R01 AI070219-02] NR 33 TC 59 Z9 64 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 29 PY 2007 VL 50 IS 24 BP 6080 EP 6094 DI 10.1021/jm070905o PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 234RR UT WOS:000251181900025 PM 17967002 ER PT J AU Jozwiak, K Ravichandran, S Collins, JR Moaddel, R Wainer, IW AF Jozwiak, Krzysztof Ravichandran, Sarangan Collins, Jack R. Moaddel, Ruin Wainer, Irving W. TI Interaction of noncompetitive inhibitors with the alpha 3 beta 2 nicotinic acetylcholine receptor investigated by affinity chromatography and molecular docking SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NONLINEAR CHROMATOGRAPHY; BINDING-SITES; CHANNELS AB A molecular model of the alpha 3 beta 2 nAChR lumen channel was constructed and hydrophobic clefts were observed near the receptor gate. Docking simulations indicated that ligand-nAChR complexes were formed by hydrophobic interactions with the cleft and hydrogen bond interactions. The equilibrium constants and association and dissociation constant rates associated with the binding interactions were determined using nonlinear chromatography on an immobilized alpha 3 beta 2 nAChR column. The computational-chromatography approach can be used to predict and describe ligand-nAChR interactions. C1 Med Univ Lublin, Dept Chem, PL-20081 Lublin, Poland. NIH, NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NCI, SAIC, Adv Biomed Comp Ctr, Ft Detrick, MD 21702 USA. RP Jozwiak, K (reprint author), Med Univ Lublin, Dept Chem, Staszicn 6, PL-20081 Lublin, Poland. EM krzysztof.jozwiak@am.lublin.pl FU Intramural NIH HHS NR 15 TC 18 Z9 18 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 29 PY 2007 VL 50 IS 24 BP 6279 EP 6283 DI 10.1021/jm070784s PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 234RR UT WOS:000251181900043 PM 17973360 ER PT J AU Cisneros, GA Elking, D Piquemal, JP Darden, TA AF Cisneros, G. Andres Elking, Dennis Piquemal, Jean-Philip Darden, Thomas A. TI Numerical fitting of molecular properties to Hermite Gaussians SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID INTERMOLECULAR INTERACTION ENERGY; ELECTROSTATIC POTENTIALS; BIOMOLECULAR SIMULATION; CHARGE-DISTRIBUTION; MODEL; MECHANICS; DENSITY; COMPUTATIONS AB A procedure is presented to fit gridded molecular properties to auxiliary basis sets (ABSs) of Hermite Gaussians, analogous to the density fitting (DF) method (Dunlap; et al. J. Chem. Phys. 1979, 71, 4993). In this procedure, the ab initio calculated properties (density, electrostatic potential, and/or electric field) are fitted via a linear- or nonlinear-least-squares procedure to auxiliary basis sets (ABS). The calculated fitting coefficients from the numerical grids are shown to be more robust than analytic density fitting due to the neglect of the core contributions. The fitting coefficients are tested by calculating intermolecular Coulomb and exchange interactions for a set of dimers. It is shown that the numerical instabilities observed in DF are caused by the attempt of the ABS to fit the core contributions. In addition, this new approach allows us to reduce the number of functions required to obtain an accurate fit. This results in decreased computational cost, which is shown by calculating the Coulomb energy of a 4096 water box in periodic boundary conditions. Using atom centered Hermite Gaussians, this calculation is only I order of magnitude slower than conventional atom-centered point charges. C1 Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ Paris 06, CNRS, UMR 7616, Chim Theor Lab, F-75252 Paris, France. RP Cisneros, GA (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RI Cisneros, Gerardo/B-3128-2010; Piquemal, Jean-Philip/B-9901-2009 OI Piquemal, Jean-Philip/0000-0001-6615-9426 FU Intramural NIH HHS [NIH0011757912, Z01 ES043010-22] NR 40 TC 16 Z9 16 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD NOV 29 PY 2007 VL 111 IS 47 BP 12049 EP 12056 DI 10.1021/jp074817r PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 234DK UT WOS:000251140700015 PM 17973464 ER PT J AU Rouse, DJ Thom, EA Spong, CY AF Rouse, Dwight J. Thom, Elizabeth A. Spong, Catherine Y. TI Progesterone and preterm birth - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CAPROATE C1 Univ Alabama, Birmingham, AL 35249 USA. George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. NICHHD, Bethesda, MD 20892 USA. RP Rouse, DJ (reprint author), Univ Alabama, Birmingham, AL 35249 USA. EM drouse@uab.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 29 PY 2007 VL 357 IS 22 BP 2307 EP 2307 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 234PQ UT WOS:000251176400020 ER PT J AU Satoh, K Hovey, RC Malewski, T Warri, A Goldhar, AS Ginsburg, E Saito, K Lydon, JP Vonderhaar, BK AF Satoh, K. Hovey, R. C. Malewski, T. Warri, A. Goldhar, A. S. Ginsburg, E. Saito, K. Lydon, J. P. Vonderhaar, B. K. TI Progesterone enhances branching morphogenesis in the mouse mammary gland by increased expression of Msx2 SO ONCOGENE LA English DT Article DE progesterone; mammary gland; msx2; homeo-box genes; branching morphogenesis ID EPITHELIAL-CELL PROLIFERATION; HEPATOCYTE GROWTH-FACTOR; SERUM-FREE CULTURE; HOMEOBOX GENES; BREAST-CANCER; RECEPTOR-B; IN-VITRO; HORMONE; MICE; PROLACTIN AB Branching morphogenesis within the peripubertal mouse mammary gland is directed by progesterone (P). A role for the homeobox-containing transcription factor, Msx2, during branching morphogenesis is suggested from its ontogenic expression pro. le and hormonal regulation. Herein, we de. ne the spatio-temporal control of Msx2 expression, the regulation of its expression by P and its direct role in ductal branching morphogenesis. P induces Msx2 in the presence of estrogen (E) both in vitro and in vivo while absence of the P receptor (PR) decreased Msx2 expression. Stable transfection of PR into mouse mammary epithelial cells increased the endogenous expression of Msx2 and their ability to undergo branching morphogenesis in vitro. Furthermore, normal mammary cells stably-transfected with Msx2 demonstrated increased branching morphogenesis in vitro while transgenic mice expressing Msx2 in their mammary glands demonstrated enhanced lateral branching during early development. The action of P on branching morphogenesis appears to involve Bmp2/4. Together, these data demonstrate that P, acting through PR-A and the Bmp2/4 pathway, induces Msx2 to enhance ductal branching in the mammary glands. C1 Natl Canc Inst, Ctr Canc Res, Mammary Biol & Tumorigenesis Lab, Bethesda, MD USA. Baylor Coll Med, Dept Cell Biol, Houston, TX USA. RP Vonderhaar, BK (reprint author), NIH, Mol & Cellular Endocrinol Sect, Mammary Biol & Tumorigenesis Lab, Bldg 37 Room 1106a1,37 Convent Dr, Bethesda, MD 20892 USA. EM bv10w@nih.gov RI Malewski, Tadeusz/H-2915-2012; Malewski, Tadeusz/J-4930-2015 OI Malewski, Tadeusz/0000-0001-8061-435X FU Intramural NIH HHS NR 38 TC 24 Z9 27 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 29 PY 2007 VL 26 IS 54 BP 7526 EP 7534 DI 10.1038/sj.onc.1210555 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 236DB UT WOS:000251282100004 PM 17546050 ER PT J AU Nomoto, M Miyata, M Shimada, M Yoshinari, K Gonzalez, FJ Shibasaki, S Kurosawa, T Shindo, Y Yamazoe, Y AF Nomoto, Masahiro Miyata, Masaaki Shimada, Miki Yoshinari, Kouichi Gonzalez, Frank J. Shibasaki, Shigeki Kurosawa, Tohru Shindo, Yasuhiro Yamazoe, Yasushi TI ME3738 protects against lithocholic acid-induced hepatotoxicity, which is associated with enhancement of biliary bile acid and cholesterol output SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ATP-binding cassette g5/8 (Abcg5/8); bile salt export pump (Bsep; abcb11); cholesterol; farnesoid x receptor (Fxr); lithocholic acid ID INDUCED LIVER TOXICITY; HYDROXYSTEROID SULFOTRANSFERASE; CANALICULAR MEMBRANE; INDUCED CHOLESTASIS; X-RECEPTOR; RAT-LIVER; DETOXIFICATION; METABOLISM; DIOSGENIN; FAILURE AB ME3738 (22 beta-methoxyolean-12-ere-3 beta, 24(4 beta)-diol), a derivative of soyasapogenol, attenuates liver disease in several models of chronic liver inflammation. In the present study, we have investigated a protective effect of ME3738 in a typical bile acid-induced cholestatic liver model, lithocholate (LCA) feeding mouse. Co-administration of ME3738 resulted in decreases in plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and hepatic bile acid level, and increases in biliary outputs of bile acid and cholesterol, as compared with the results in mice treated with LCA alone. LCA sulfation by hydroxysteroid sulfotransferase 2a and hydroxylation have been reported to be involved in protection against LCA-induced hepatotoxicity. ME3738-treattnent, however, had no clear influence on the hydroxysteroid sulfotransferase 2a protein level and LCA 6 alpha-. 6 beta- and 7 alpha-hydroxylase activities, but increased biliary cholesterol output. Cholate (CA)-treatment has been shown to induce hepatotoxicity in farnesoid X receptor-null mice, which is scarcely dependent on bile acid sulfation and hydroxylation but associated with decreased biliary bile acid output. Co-administration of ME3738 decreased the ALT and ALP activities and hepatic bile acid level, and increased biliary outputs of bile acid and cholesterol in farnesoid X receptor-null mice, as compared with the results in the mice treated with CA. Moreover, a clear correlation between biliary outputs of cholesterol and bile acid was observed in these two bile acid-induced hepatotoxicity mouse models. These results suggest that ME3738 protects against bile acid-induced hepatotoxicity through increased biliary bile acid output that is not related to bile acid metabolism but associated with cholesterol output. (c) 2007 Elsevier B.V All rights reserved. C1 Tohoku Univ, Grad Sch Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Aoba Ku, Sendai, Miyagi 9808578, Japan. Meiji Seika Kaisha Ltd, Pharmaceut Res Ctr, Toxicol & Pharmacokinet Res Labs, Yokohama, Kanagawa 2228567, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Tohoku Univ, Ctr Excellence Program 21st, CRESCENDO, Sendai, Miyagi 9808578, Japan. RP Miyata, M (reprint author), Tohoku Univ, Grad Sch Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Aoba Ku, Sendai, Miyagi 9808578, Japan. EM nuyata@mail.phann.tohoku.ac.jp NR 29 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 28 PY 2007 VL 574 IS 2-3 BP 192 EP 200 DI 10.1016/i.ejphar.2007.07.004 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 231JK UT WOS:000250942800014 PM 17651726 ER PT J AU Wasko, MCM Hubert, HB Lingala, VB Elliott, JR Luggen, ME AF Wasko, Mary Chester M. Hubert, Helen B. Lingala, Vijaya Bharathi Elliott, Jennifer Rae Luggen, Michael E. TI Risk of diabetes in patients with rheumatoid arthritis taking hydroxychloroquine - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID LOW-DOSE PREDNISOLONE; CONTROLLED-TRIAL; DOUBLE-BLIND; THERAPY C1 Univ Pittsburgh, Div Clin Immunol & Rheumatol, Pittsburgh, PA 15260 USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. Univ Cincinnati, Div Immunol, Cincinnati, OH USA. NIAMSD, Bethesda, MD 20892 USA. RP Wasko, MCM (reprint author), Univ Pittsburgh, Div Clin Immunol & Rheumatol, Pittsburgh, PA 15260 USA. EM wasko@pitt.edu NR 6 TC 0 Z9 0 U1 0 U2 0 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 NOV 28 PY 2007 VL 298 IS 20 BP 2369 EP 2370 DI 10.1001/jama.298.20.2369 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 234KR UT WOS:000251163400015 ER PT J AU Gifondorwa, DJ Robinson, MB Hayes, CD Taylor, AR Prevette, DM Oppenheim, RW Caress, J Milligan, CE AF Gifondorwa, David J. Robinson, Mac B. Hayes, Crystal D. Taylor, Anna R. Prevette, David M. Oppenheim, Ronald W. Caress, James Milligan, Carolanne E. TI Exogenous delivery of heat shock protein 70 increases lifespan in a mouse model of amyotrophic lateral sclerosis SO JOURNAL OF NEUROSCIENCE LA English DT Article DE motoneuron; denervation; NMJ; axonopathy; neurodegeneration; SOD1 ID HEAT-SHOCK PROTEINS; SUPEROXIDE-DISMUTASE; MOTOR-NEURONS; TRANSGENIC MODEL; PROLONGS SURVIVAL; STRESS-RESPONSE; DISEASE ONSET; SPINAL-CORD; IN-VIVO; ALS AB Amyotrophic lateral sclerosis ( ALS) is a debilitating neurodegenerative disorder that results in the progressive loss of motoneurons ( MNs) in the CNS. Several survival and death mechanisms of MNs have been characterized and it has been determined that MNs do not appear to mount a complete stress response, as determined by the lack of heat shock protein 70 ( Hsp70) upregulation after several stress paradigms. Hsp70 has been shown to confer neuroprotection and the insufficient availability of Hsp70 may contribute to MNs' susceptibility to death in ALS mice. In this study, recombinant human Hsp70 ( rhHsp70) was intraperitoneally injected three times weekly, beginning at postnatal day 50 until endstage, to G93A mutant SOD1 ( G93A SOD1) mice. The administration of rhHsp70 was effective at increasing lifespan, delaying symptom onset, preserving motor function and prolonging MN survival. Interestingly, injected rhHsp70 localized to skeletal muscle and was not readily detected in the CNS. Treatment with rhHsp70 also resulted in an increased number of innervated neuromuscular junctions compared with control tissue. Together these results suggest rhHsp70 may delay disease progression in the G93A SOD1 mouse via a yet to be identified peripheral mechanism. C1 Wake Forest Univ, Sch Med, Dept Neurobiol & Anat, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Neurol, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Program Neurosci, Winston Salem, NC 27157 USA. Natl Inst Neurol Disorder & Stroke, Bethesda, MD 20892 USA. RP Milligan, CE (reprint author), Wake Forest Univ, Sch Med, Dept Neurobiol & Anat, Winston Salem, NC 27157 USA. EM milligan@wfubmc.edu OI Taylor, Anna/0000-0002-6501-3393; Caress, James/0000-0002-5814-6083 FU NINDS NIH HHS [NS36081, NS46615] NR 67 TC 73 Z9 76 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 28 PY 2007 VL 27 IS 48 BP 13173 EP 13180 DI 10.1523/JNEUROSCI.4057-07.2007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 236IO UT WOS:000251296700014 PM 18045911 ER PT J AU Cellmer, T Henry, ER Kubelka, J Hofrichter, J Eaton, WA AF Cellmer, Troy Henry, Eric R. Kubelka, Jan Hofrichter, James Eaton, William A. TI Relaxation rate for an ultrafast folding protein is independent of chemical denaturant concentration SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID TRANSITION-STATE; DIFFUSION; DYNAMICS; KINETICS; MODEL AB The connection between free-energy surfaces and chevron plots has been investigated in a laser temperature jump kinetic study of a small ultrafast folding protein, the 35-residue subdomain from the villin headpiece. Unlike all other proteins that have been studied so far, no measurable dependence of the unfolding/refolding relaxation rate on denaturant concentration was observed over a wide range of guanidinium chloride concentration. Analysis with a simple Ising-like theoretical model shows that this denaturant-invariant relaxation rate can be explained by a large movement of the major free energy barrier, together with a denaturant- and reaction coordinate-dependent diffusion coefficient. C1 NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. Univ Wyoming, Dept Chem, Laramie, WY 82071 USA. RP Eaton, WA (reprint author), NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. EM eaton@helix.nih.gov RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 FU Intramural NIH HHS NR 16 TC 35 Z9 35 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 28 PY 2007 VL 129 IS 47 BP 14564 EP + DI 10.1021/ja0761939 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 234DZ UT WOS:000251142200018 PM 17983235 ER PT J AU Hanna, MC Calkins, DJ AF Hanna, Michael C. Calkins, David J. TI Expression of genes encoding glutamate receptors and transporters in rod and cone bipolar cells of the primate retina determined by single-cell polymerase chain reaction SO MOLECULAR VISION LA English DT Article ID MACAQUE MONKEY RETINA; PARASOL GANGLION-CELLS; RAT RETINA; MAMMALIAN RETINA; KAINATE RECEPTORS; VERTEBRATE RETINA; MESSENGER-RNA; IMMUNOCYTOCHEMICAL ANALYSIS; DIFFERENTIAL EXPRESSION; FUNCTIONAL-ORGANIZATION AB Purpose: Light signals from rod and cone photoreceptors traverse distinct types of second-order, bipolar neurons that carry these signals from the outer to inner retina. Anatomical and physiological studies suggest that the specialization of rod and cone bipolar cells involves the differential expression of proteins involved in glutamatergic signaling. In a previous study, we compared the expression of genes for the AMPA- (GluR1-4) and kainate-sensitive (GluR5-7, KA1-2) ionotropic glutamate receptors, the metabotropic glutamate receptors (mGluR1-8), and five non-vesicular glutamate transporters (EAAT1-5) in full-complement cDNA constructed from fresh and aldehyde-fixed macaque retina using a technique suitable for amplification of a variety of differentially expressed transcripts. Here we apply the same protocol to compare expression of these genes in cDNA constructed from single rod and cone bipolar cells previously-labeled for morphological identification in fixed slices of macaque retina. Methods: We used immunocytochemical labeling and unique morphological features in lightly fixed slices of macaque retina to target the rod bipolar or the DB3 cone OFF bipolar cell. Under visual control, we used a micropipette to target and extract labeled cells, and we isolated mRNA from each through enzymatic digestion. Full-length cDNA was synthesized using 3'-end amplification (TPEA) PCR, in which the highly diverse 3' regions were amplified indiscriminately to ensure detection of both high and low abundance genes. We used gene-specific RT-PCR to probe the cDNA of each bipolar cell both for expression of known genes to confirm cell identification as well as expression of genes encoding glutamate receptors GluR1-7, KA1-2, and mGluR1-8 and for transporters EAAT1-5. Results: Of 27 rod bipolar cells confirmed to express the genes for the a subunit of protein kinase C, mGluR6, and its G protein G alpha(o), 26 expressed at least one AMPA GluR subunit gene, 16 expressed at least two, and nine expressed three or more. Nearly every cell expressed the GluR4 gene (23/27), followed by GluR2 (16/27) and GluR1 (11/27). In addition to mGluR6, 20/27 cells also expressed the mGluR3 gene. Nearly every rod bipolar cell also expressed the genes for the EAAT2 (23/27) and EAAT4 (21/27) transporters. Of 26 DB3 cells confirmed by expression of calbindin D-28 and absence of GAD-65/67, each expressed the gene for the AMPA subunit GluR4, followed by GluR2 (22/26), and GluR1 (15/26), the only kainate subunit gene expressed was GluR6 (18/26). Nearly every DB3 cell also expressed the gene for the EAAT2 transporter (25/26), but no others. Conclusions: Rod bipolar cells in the Macaca monkey retina expressed not only the mGluR6 gene, a subunit necessary for transmission of light-ON signals, but also nearly always GluR4 in combination with the glutamate transporter EAAT4 (21/27 cells). The DB3 cell involved in processing light-OFF signals from cones expressed most highly the combination of GluR4 and the transporter EAAT2 (25/26). These results suggest that glutamatergic signaling in rod and cone circuits in the primate retina depends upon complex molecular interactions, involving not only multiple glutamate receptor sub-units, but also glutamate transporters. Our data demonstrate a consistent primary pattern for each cell type with subtle variability involving other genes. Thus, like neuronal cell types in other brain regions, morphological and physiological homogeneity among retinal bipolar cell types does not exclude variations in expression that could serve to adjust the stimulus-response profile of each cell. C1 [Calkins, David J.] Vanderbilt Univ, Vanderbilt Eye Inst, Dept Ophthalmol & Visual Sci, Med Ctr, Nashville, TN 37232 USA. [Hanna, Michael C.] Natl Inst Neurol Disorders & Stroke, NIH, Cellular Neurol Unit, Bethesda, MD USA. RP Calkins, DJ (reprint author), Vanderbilt Univ, Vanderbilt Eye Inst, Dept Ophthalmol & Visual Sci, Med Ctr, 8000 Med Ctr E, Nashville, TN 37232 USA. EM david.j.calkins@vanderbilt.edu FU NEI NIH HHS [EY12480]; NIA NIH HHS [AG024258] NR 79 TC 11 Z9 11 U1 0 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD NOV 28 PY 2007 VL 13 IS 249-51 BP 2194 EP 2208 PG 15 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 310RA UT WOS:000256546500001 PM 18087239 ER PT J AU Iser, WB Wolkow, CA AF Iser, Wendy B. Wolkow, Catherine A. TI DAF-2/Insulin-Like Signaling in C. elegans Modifies Effects of Dietary Restriction and Nutrient Stress on Aging, Stress and Growth SO PLOS ONE LA English DT Article AB Background. Dietary restriction (DR) and reduced insulin/IGF-I-like signaling (IIS) are two regimens that promote longevity in a variety of organisms. Genetic analysis in C. elegans nematodes has shown that DR and IIS couple to distinct cellular signaling pathways. However, it is not known whether these pathways ultimately converge on overlapping or distinct targets to extend lifespan. Principal Findings. We investigated this question by examining additional effects of DR in wildtype animals and in daf-2 mutants with either moderate or severe IIS deficits. Surprisingly, DR and IIS had opposing effects on these physiological processes. First, DR induced a stress-related change in intestinal vesicle trafficking, termed the FIRE response, which was suppressed in daf-2 mutants. Second, DR did not strongly affect expression of a daf-2- and stress-responsive transcriptional reporter. Finally, DR-related growth impairment was suppressed in daf-2 mutants. Conclusions. These findings reveal that an important biological function of DAF-2/IIS is to enhance growth and survival under nutrient-limited conditions. However, we also discovered that levels of DAF-2 pathway activity modified the effects of DR on longevity. Thus, while DR and IIS clearly affect lifespan through independent targets, there may also be some prolongevity targets that are convergently regulated by these pathways. C1 [Iser, Wendy B.; Wolkow, Catherine A.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Wolkow, CA (reprint author), NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM wolkowca@grc.nia.nih.gov FU NIA Intramural Research Program; New Scholar in Aging Award from the Ellison Medical Foundation FX This work was funded by the NIA Intramural Research Program and by a New Scholar in Aging Award from the Ellison Medical Foundation (CAW). Funding sources were not involved in any aspect of the study or manuscript preparation and submission. NR 44 TC 14 Z9 21 U1 2 U2 11 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 NOV 28 PY 2007 VL 2 IS 11 AR e1240 DI 10.1371/journal.pone.0001240 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JC UT WOS:000207459300021 PM 18043747 ER PT J AU Luca, S Yau, WM Leapman, R Tycko, R AF Luca, Sorin Yau, Wai-Ming Leapman, Richard Tycko, Robert TI Peptide conformation and supramolecular organization in amylin fibrils: Constraints from solid-state NMR SO BIOCHEMISTRY LA English DT Article ID ISLET AMYLOID POLYPEPTIDE; NUCLEAR-MAGNETIC-RESONANCE; PARALLEL BETA-SHEET; TYPE-2 DIABETES-MELLITUS; ANGLE-SPINNING NMR; SECONDARY-STRUCTURE; FULL-LENGTH; STRUCTURAL MODEL; DISTANCE MEASUREMENTS; ROTATIONAL RESONANCE AB The 37-residue amylin peptide, also known as islet amyloid polypeptide, forms fibrils that are the main peptide or protein component of amyloid that develops in the pancreas of type 2 diabetes patients. Amylin also readily forms amyloid fibrils in vitro that are highly polymorphic under typical experimental conditions. We describe a protocol for the preparation of synthetic amylin fibrils that exhibit a single predominant morphology, which we call a striated ribbon, in electron microscopy and atomic force microscopy images. Solid-state nuclear magnetic resonance (NMR) measurements on a series of isotopically labeled samples indicate a single molecular structure within the striated ribbons. We use scanning transmission electron microscopy and several types of one- and two-dimensional solid-state NMR techniques to obtain constraints on the peptide conformation and supramolecular structure in these amylin fibrils and to derive molecular structural models that are consistent with the experimental data. The basic structural unit in amylin striated ribbons, which we call the protofilament, contains four layers of parallel beta-sheets, formed by two symmetric layers of amylin molecules. The molecular structure of amylin protofilaments in striated ribbons closely resembles the protofilament in amyloid fibrils with a similar morphology formed by the 40-residue beta-amyloid peptide that is associated with Alzheimer's disease. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Biomed Imaging & Bioengn, Div Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU Intramural NIH HHS [Z01 DK029062-01] NR 97 TC 290 Z9 293 U1 5 U2 61 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 27 PY 2007 VL 46 IS 47 BP 13505 EP 13522 DI 10.1021/bi701427q PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 234GZ UT WOS:000251150000005 PM 17979302 ER PT J AU Makarova, KS Sorokin, AV Novichkov, PS Wolf, YI Koonin, EV AF Makarova, Kira S. Sorokin, Alexander V. Novichkov, Pavel S. Wolf, Yuri I. Koonin, Eugene V. TI Clusters of orthologous genes for 41 archaeal genomes and implications for evolutionary genomics of archaea SO BIOLOGY DIRECT LA English DT Article ID METHANOSARCINA-MAZEI; FUNCTIONAL GENOMICS; PROTEIN FAMILIES; COG DATABASE; SEQUENCE; PROKARYOTES; REVEALS; CRENARCHAEON; BACTERIAL; PHYLOGENY AB Background: An evolutionary classification of genes from sequenced genomes that distinguishes between orthologs and paralogs is indispensable for genome annotation and evolutionary reconstruction. Shortly after multiple genome sequences of bacteria, archaea, and unicellular eukaryotes became available, an attempt on such a classification was implemented in Clusters of Orthologous Groups of proteins (COGs). Rapid accumulation of genome sequences creates opportunities for refining COGs but also represents a challenge because of error amplification. One of the practical strategies involves construction of refined COGs for phylogenetically compact subsets of genomes. Results: New Archaeal Clusters of Orthologous Genes (arCOGs) were constructed for 41 archaeal genomes (13 Crenarchaeota, 27 Euryarchaeota and one Nanoarchaeon) using an improved procedure that employs a similarity tree between smaller, group-specific clusters, semi-automatically partitions orthology domains in multidomain proteins, and uses profile searches for identification of remote orthologs. The annotation of arCOGs is a consensus between three assignments based on the COGs, the CDD database, and the annotations of homologs in the NR database. The 7538 arCOGs, on average, cover similar to 88% of the genes in a genome compared to a similar to 76% coverage in COGs. The finer granularity of ortholog identification in the arCOGs is apparent from the fact that 4538 arCOGs correspond to 2362 COGs; similar to 40% of the arCOGs are new. The archaeal gene core (protein-coding genes found in all 41 genome) consists of 166 arCOGs. The arCOGs were used to reconstruct gene loss and gene gain events during archaeal evolution and gene sets of ancestral forms. The Last Archaeal Common Ancestor (LACA) is conservatively estimated to possess 996 genes compared to 1245 and 1335 genes for the last common ancestors of Crenarchaeota and Euryarchaeota, respectively. It is inferred that LACA was a chemoautotrophic hyperthermophile that, in addition to the core archaeal functions, encoded more idiosyncratic systems, e. g., the CASS systems of antivirus defense and some toxin-antitoxin systems. Conclusion: The arCOGs provide a convenient, flexible framework for functional annotation of archaeal genomes, comparative genomics and evolutionary reconstructions. Genomic reconstructions suggest that the last common ancestor of archaea might have been (nearly) as advanced as the modern archaeal hyperthermophiles. ArCOGs and related information are available at: ftp://ftp.ncbi.nih.gov/pub/koonin/arCOGs/. C1 [Makarova, Kira S.; Sorokin, Alexander V.; Novichkov, Pavel S.; Wolf, Yuri I.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM makarova@ncbi.nlm.nih.gov; sorokin@ncbi.nlm.nih.gov; novichko@ncbi.nlm.nih.gov; wolf@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 83 TC 107 Z9 109 U1 1 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD NOV 27 PY 2007 VL 2 AR 33 DI 10.1186/1745-6150-2-33 PG 20 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 259FF UT WOS:000252923800001 PM 18042280 ER PT J AU Koshiol, J Qiao, YL Mark, SD Dawsey, SM Abnet, CC Kamangar, F Lennette, ET Dong, ZW Taylor, PR AF Koshiol, J. Qiao, Y-L Mark, S. D. Dawsey, S. M. Abnet, C. C. Kamangar, F. Lennette, E. T. Dong, Z-W Taylor, P. R. TI Epstein-Barr virus serology and gastric cancer incidence and survival SO BRITISH JOURNAL OF CANCER LA English DT Article DE eBV; gastric cancer; incidence; survival ID GENERAL-POPULATION; INVOLVEMENT; ESOPHAGEAL; CARCINOMA; LINXIAN; CHINA AB Among 185 cases of gastric cancer and 200 controls in Linxian, China, Epstein - Barr virus (EBV) seropositivity was not associated with increased risk of gastric cancer. High EBV nuclear antigen titres were associated with longer survival in cardia cancer cases, possibly due to chance. C1 Natl Canc Inst, Div Canc Prevent, Canc Prevent Fellowship, Bethesda, MD 20892 USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. Univ Colorado, Med Ctr, Dept Prevent Med & Biometr, Boulder, CO 80309 USA. Nectandra Inst, San Ramon, CA USA. RP Koshiol, J (reprint author), Natl Canc Inst, Div Canc Prevent, Canc Prevent Fellowship, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM koshiolj@mail.nih.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 9 TC 7 Z9 7 U1 0 U2 3 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 NOV 27 PY 2007 VL 97 IS 11 BP 1567 EP 1569 DI 10.1038/sj.bjc.6604063 PG 3 WC Oncology SC Oncology GA 234OF UT WOS:000251172700016 PM 17987041 ER PT J AU Hsing, AW Gao, YT Han, TQ Rashid, A Sakoda, LC Wang, BS Shen, MC Zhang, BH Niwa, S Chen, J Fraumeni, JF AF Hsing, A. W. Gao, Y-T Han, T-Q Rashid, A. Sakoda, L. C. Wang, B-S Shen, M-C Zhang, B-H Niwa, S. Chen, J. Fraumeni, J. F., Jr. TI Gallstones and the risk of biliary tract cancer: a population-based study in China SO BRITISH JOURNAL OF CANCER LA English DT Article DE biliary tract cancer; gallstones; cholecystitis; China ID GALLBLADDER CANCER; BILE-ACIDS; EPIDEMIOLOGY; CARCINOMA; SHANGHAI; DISEASE; CHOLESTEROL; BACTERIA; SERUM; DUCT AB We conducted a population-based study of 627 patients with biliary tract cancers (368 of gallbladder, 191 bile duct, and 68 ampulla of Vater), 1037 with biliary stones, and 959 healthy controls randomly selected from the Shanghai population, all personally interviewed. Gallstone status was based on information from self-reports, imaging procedures, surgical notes, and medical records. Among controls, a transabdominal ultrasound was performed to detect asymptomatic gallstones. Gallstones removed from cancer cases and gallstone patients were classified by size, weight, colour, pattern, and content of cholesterol, bilirubin, and bile acids. Of the cancer patients, 69% had gallstones compared with 23% of the population controls. Compared with subjects without gallstones, odds ratios associated with gallstones were 23.8 (95% confidence interval (CI), 17.0-33.4), 8.0 (95% CI 5.6-11.4), and 4.2 (95% CI 2.5-7.0) for cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, respectively, persisting when restricted to those with gallstones at least 10 years prior to cancer. Biliary cancer risks were higher among subjects with both gallstones and self-reported cholecystitis, particularly for gallbladder cancer (OR = 34.3, 95% CI 19.9-59.2). Subjects with bile duct cancer were more likely to have pigment stones, and with gallbladder cancer to have cholesterol stones (P < 0.001). Gallstone weight in gallbladder cancer was significantly higher than in gallstone patients (4.9 vs 2.8 grams; P = 0.001). We estimate that in Shanghai 80% (95% CI 75-84%), 59% (56-61%), and 41% (29-59%) of gallbladder, bile duct, and ampulla of Vater cancers, respectively, could be attributed to gallstones. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. Shanghai Canc Inst, Shanghai, Peoples R China. Shanghai Med Univ 2, Ruijin Hosp, Shanghai, Peoples R China. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. Shanghai Tumor Hosp, Shanghai, Peoples R China. Second Mil Med Univ, Inst Oriental Hepatobiliary Surg, Shanghai, Peoples R China. Westat Corp, Rockville, MD USA. Univ Penn, Philadelphia, PA 19104 USA. RP Hsing, AW (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, EPS 5024,MSC7234,6120 Execut Blvd, Bethesda, MD 20852 USA. EM hsinga@mail.nih.gov FU Intramural NIH HHS NR 31 TC 80 Z9 85 U1 4 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 27 PY 2007 VL 97 IS 11 BP 1577 EP 1582 DI 10.1038/sj.bjc.6604047 PG 6 WC Oncology SC Oncology GA 234OF UT WOS:000251172700018 PM 18000509 ER PT J AU McMahon, A Jackson, SN Woods, AS Kedzierski, W AF McMahon, Anne Jackson, Shelley N. Woods, Amina S. Kedzierski, Wojciech TI A Stargardt disease-3 mutation in the mouse Elovl4 gene causes retinal deficiency of C32-C36 acyl phosphatidylcholines SO FEBS LETTERS LA English DT Article DE Stargardt disease-3; retina; very long chain fatty acid; phosphatidylcholine; unfolded-protein response; mass spectrometry ID PERMEABILITY BARRIER FUNCTION; MACULAR DYSTROPHY; LONG-CHAIN; FATTY-ACIDS; WILD-TYPE; PROTEIN; MICE; DEGENERATION; MECHANISM; DISEASE AB Stargardt disease-3 (STGD3) is a juvenile dominant macular degeneration caused by mutations in elongase of very long chain fatty acid-4. All identified mutations produce a truncated protein which lacks a motif for protein retention in endoplasmic reticulum, the site of fatty acid synthesis. In these studies of Stgd3-knockin mice carrying a human pathogenic mutation, we examined two potential pathogenic mechanisms: truncated protein-induced cellular stress and lipid product deficiency. Analysis of mutant retinas detected no cellular stress but demonstrated selective deficiency of C32-C36 acyl phosphatidylcholines. We conclude that this deficit leads to the human STGD3 pathology. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 [McMahon, Anne; Kedzierski, Wojciech] Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 USA. [Jackson, Shelley N.; Woods, Amina S.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Kedzierski, W (reprint author), Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Wojciech.Kedzierski@UTSouthwestern.edu FU Intramural NIH HHS; NEI NIH HHS [R03 EY015409, EY 15409, R03 EY015409-01, R03 EY015409-02, R03 EY015409-03] NR 23 TC 43 Z9 44 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 27 PY 2007 VL 581 IS 28 BP 5459 EP 5463 DI 10.1016/j.febslet.2007.10.050 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 267CV UT WOS:000253487900021 PM 17983602 ER PT J AU Best, RB Merchant, KA Gopich, IV Schuler, B Bax, A Eaton, WA AF Best, Robert B. Merchant, Kusai A. Gopich, Irina V. Schuler, Benjamin Bax, Ad Eaton, William A. TI Effect of flexibility and cis residues in single-molecule FRET studies of polyproline SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fluorescence; molecular dynamics; persistence length; polypeptide; proteins ID RESONANCE ENERGY-TRANSFER; TRANSFER CONFOCAL MICROSCOPY; POLY-L-PROLINE; FLUORESCENCE SPECTROSCOPY; PHOTON STATISTICS; PROTEIN COLLAPSE; DYNAMICS; RULER; DISTRIBUTIONS; SIMULATIONS AB Polyproline has recently been used as a spacer between donor and acceptor chromophores to help establish the accuracy of distances determined from single-molecule Forster resonance energy transfer (FRET) measurements. This work showed that the FRET efficiency in water is higher than expected for a rigid spacer and was attributed to the flexibility of the polypeptide. Here, we investi gate this issue further, using a combination of single-molecule fluorescence intensity and lifetime measurements, NMR, theory, and molecular dynamics simulations of polyproline-20 that include the dyes and their linkers to the polypepticle. NMR shows that in water approximate to 30% of the molecules contain internal cis prolines, whereas none are detectable in trifluoroethanol. Simulations suggest that the all-trans form of polyproline is relatively stiff, with persistence lengths of 9-13 nm using different established force fields, and that the kinks arising from internal cis prolines are primarily responsible for the higher mean FRET efficiency in water. We show that the observed efficiency histograms and distributions of donor fluorescence lifetimes are explained by the presence of multiple species with efficiencies consistent with the simulations and populations determined by NMR. In calculating FRET efficiencies from the simulation, we find that the fluctuations of the chromophores, attached to long flexible linkers, also play an important role. A similar simulation approach suggests that the flexibility of the chromophore linkers is largely responsible forthe previously unexplained high value of R-0 required to fit the data in the classic study of Stryer and Haugland. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland. RP Best, RB (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England. EM rbb24@cam.ac.uk; eaton@helix.nih.gov RI Schuler, Benjamin/E-7342-2011 OI Schuler, Benjamin/0000-0002-5970-4251 FU Intramural NIH HHS NR 34 TC 116 Z9 117 U1 2 U2 55 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 NOV 27 PY 2007 VL 104 IS 48 BP 18964 EP 18969 DI 10.1073/pnas.0709567104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 239DK UT WOS:000251498700019 PM 18029448 ER PT J AU Ramon-Maiques, S Kuo, AJ Carney, D Matthews, AGW Oettinger, MA Gozani, O Yang, W AF Ramon-Maiques, Santiago Kuo, Alex J. Carney, Dylan Matthews, Adam G. W. Oettinger, Marjorie A. Gozani, Or Yang, Wei TI The plant homeodomain finger of RAG2 recognizes histone H3 methylated at both lysine-4 and arginine-2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE H3K4me; regulation; V(D)J recombination; H3R2me; SCID ID V(D)J RECOMBINATION; PHD FINGER; STRUCTURAL BASIS; C-TERMINUS; CHROMATIN MODIFICATIONS; MOLECULAR-BASIS; B-CELL; GENE; DOMAIN; CHROMODOMAIN AB Recombination activating gene (RAG) 1 and RAG2 together catalyze V(D)J gene rearrangement in lymphocytes as the first step in the assembly and maturation of antigen receptors. RAG2 contains a plant homeodomain (PHD) near its C terminus (RAG2-PHD) that recognizes histone H3 methylated at lysine 4 (H3K4me) and influences V(D)J recombination. We report here crystal structures of RAG2-PHD alone and complexed with five modified H3 peptides. Two aspects of RAG2-PHD are unique. First, in the absence of the modified peptide, a peptide N-terminal to RAG2-PHD occupies the substrate-binding site, which may reflect an autoregulatory mechanism. Second, in contrast to other H3K4me3-binding PHD domains, RAG2-PHD substitutes a carboxylate that interacts with arginine 2 (112) with a Tyr, resulting in binding to H3K4me3 that is enhanced rather than inhibited by dimethylation of R2. Five residues involved in histone H3 recognition were found mutated in severe combined immunodeficiency (SCID) patients. Disruption of the RAG2-PHD structure appears to lead to the absence of T and B lymphocytes, whereas failure to bind H3K4me3 is linked to Omenn Syndrome. This work provides a molecular basis for chromatin-dependent gene recombination and presents a single protein domain that simultaneously recognizes two distinct histone modifications, revealing added complexity in the read-out of combinatorial histone modifications. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Yang, W (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM wei.yang@nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU Intramural NIH HHS NR 50 TC 131 Z9 132 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 27 PY 2007 VL 104 IS 48 BP 18993 EP 18998 DI 10.1073/pnas.0709170104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 239DK UT WOS:000251498700024 PM 18025461 ER PT J AU Best, RB Merchant, KA Gopich, IV Schuler, B Bax, A Eaton, WA AF Best, Robert B. Merchant, Kusai A. Gopich, Irina V. Schuler, Benjamin Bax, Ad Eaton, William A. TI Effect of flexibility and cis residues in single-molecule FRET studies of polyproline SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fluorescence; molecular dynamics; persistence length; polypeptide; proteins ID DENDRITIC CELL-POPULATIONS; LANGERHANS CELLS; STEADY-STATE; T-CELLS; CONTACT HYPERSENSITIVITY; LYMPH-NODES; BONE-MARROW; IN-VIVO; EPITHELIAL-CELLS; ESTROUS-CYCLE AB Polyproline has recently been used as a spacer between donor and acceptor chromophores to help establish the accuracy of distances determined from single-molecule Forster resonance energy transfer (FRET) measurements. This work showed that the FRET efficiency in water is higher than expected for a rigid spacer and was attributed to the flexibility of the polypeptide. Here, we investigate this issue further, using a combination of single-molecule fluorescence intensity and lifetime measurements, NMR, theory, and molecular dynamics simulations of polyproline-20 that include the dyes and their linkers to the polypeptide. NMR shows that in water approximate to 30% of the molecules contain internal cis prolines, whereas none are detectable in trifluoroethanol. Simulations suggest that the all-trans form of polyproline is relatively stiff, with persistence lengths of 9 - 13 nm using different established force fields, and that the kinks arising from internal cis prolines are primarily responsible for the higher mean FRET efficiency in water. We show that the observed efficiency histograms and distributions of donor fluorescence lifetimes are explained by the presence of multiple species with efficiencies consistent with the simulations and populations determined by NMR. In calculating FRET efficiencies from the simulation, we find that the fluctuations of the chromophores, attached to long flexible linkers, also play an important role. A similar simulation approach suggests that the flexibility of the chromophore linkers is largely responsible for the previously unexplained high value of R-0 required to fit the data in the classic study of Stryer and Haugland. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland. RP Best, RB (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England. EM rbb24@cam.ac.uk RI Schuler, Benjamin/E-7342-2011; Best, Robert/H-7588-2016 OI Schuler, Benjamin/0000-0002-5970-4251; Best, Robert/0000-0002-7893-3543 NR 42 TC 2 Z9 2 U1 0 U2 11 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 NOV 27 PY 2007 VL 104 IS 48 BP 19064 EP 19066 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 239DK UT WOS:000251498700037 ER PT J AU Santomasso, BD Roberts, WK Thomas, A Williams, T Blachere, NE Dudley, ME Houghton, AN Posner, JB Darnell, RB AF Santomasso, Bianca D. Roberts, Wendy K. Thomas, Ashby Williams, Travis Blachere, Nathalie E. Dudley, Mark E. Houghton, Alan N. Posner, Jerome B. Darnell, Robert B. TI A T cell receptor associated with naturally occurring human tumor immunity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene therapy; gynecologic cancer; paraneoplastic cerebellar degeneration ID PARANEOPLASTIC CEREBELLAR DEGENERATION; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I; TRANSGENIC MICE; INTERFERON-GAMMA; GENE-TRANSFER; HIGH-AFFINITY; HIGH AVIDITY; ANTIGEN; TCR AB The onconeural antigens appear to serve as tumor rejection antigens in the paraneoplastic neurologic disorders. Here, we used an unbiased peptide binding screen, followed by studies in HLA-A2.1 transgenic mice to identify naturally processed HLA-A2.1 restricted epitopes of the paraneoplastic cerebellar degeneration breast/ ovarian cancer antigen cdr2. These mice were used to clone high-avidity cdr2-specific CD8(+) T cells that recognize human tumor cells presenting endogenously loaded MHC class I-cdr2 peptide. T cells with this specificity were detected in the peripheral blood of two HLA-A2.1(+) paraneoplastic cerebellar degeneration patients. We cloned T cell receptor (TCR) alpha and beta genes from cdr2-specific T cells; electroporation of RNA encoding this TCR turned nonreactive donor T cells into efficient killers of human cdr2-expressing tumor cells. Cloned cdr2-specific TCR genes provide a clinically relevant means for immunologic targeting of human gynecologic cancers. C1 Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. Rockefeller Univ, Mol Neurooncol Lab, New York, NY 10065 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Lab Tumor Immunol, New York, NY 10065 USA. RP Darnell, RB (reprint author), Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. EM darnelr@rockefeller.edu RI Darnell, Robert/B-9022-2008 OI Darnell, Robert/0000-0002-5134-8088 FU NCI NIH HHS [R01 CA085784, R01 CA085784-01A2, R01 CA085784-02, R01 CA085784-03, R01 CA085784-04, R01 CA085784-05, R01 CA85784]; NCRR NIH HHS [M01 RR000102-410316, 1UL1RR024143, M01 RR000102, M01 RR000102-36A10316, M01 RR000102-36A10361, M01 RR000102-370316, M01 RR000102-370361, M01 RR000102-380316, M01 RR000102-380361, M01 RR000102-390316, M01 RR000102-400316, M01-RR00102, UL1 RR024143]; NIGMS NIH HHS [GM07739, T32 GM007739] NR 47 TC 22 Z9 22 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 27 PY 2007 VL 104 IS 48 BP 19073 EP 19078 DI 10.1073/pnas.0704336104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 239DK UT WOS:000251498700039 PM 18045792 ER PT J AU Chen, HY Di Mascio, M Perelson, AS Ho, DD Zhang, LQ AF Chen, Hannah Yuan Di Mascio, Michele Perelson, Alan S. Ho, David D. Zhang, Linqi TI Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dynamic; HIV; highly active antiretroviral therapy; half-life; modeling ID SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; POLYMERASE CHAIN-REACTION; HIV-1 INFECTION; CLEARANCE RATE; LYMPHOCYTES; PLASMA; INTEGRATION; ASSAY; TRANSMISSION AB A single-cycle simian immunodeficiency virus (scSIV) that undergoes only one round of infection and replication was constructed to calculate the total number of virons produced by an SIV-infected cell in vivo. Four Mamu-A*01 rhesus macaques were inoculated on two occasions 11 weeks apart with the scSIV by ex vivo infection and i.v. reinfusion of autologous cells. After each inoculation, plasma viral loads peaked between 1 and 2.5 days and then declined exponentially in one or two phases to below detection limits within 2 weeks. Although higher levels of SIV-specific cytotoxic T lymphocytes and modest increases in antibody responses were observed for each animal after the second inoculation, decay rates of the infected cells were only minimally affected. Analyzing the viral load data with a mathematical model, the in vivo viral burst size averaged 4.0 x 10(4) and 5.5 x 10(4) virions per cell for the first and second inoculations, respectively, with no significant difference between the two inoculations. This estimate, in conjunction with our prior understanding of other quantitative viral and cellular parameters during SIV and HIV infection, provides critical insights into the dynamic process of viral production and its interplay with the infected host in vivo. C1 Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. NIAID, NIH, Bethesda, MD 20892 USA. Los Alamos Natl Lab, Div Theoret, Los Alamos, NM 87545 USA. Chinese Acad Med Sci, Inst Pathogen Biol, AIDS Res Ctr, Beijing 100730, Peoples R China. Tsing Hua Univ, Peking Union Med Coll, Beijing 100730, Peoples R China. RP Zhang, LQ (reprint author), Rockefeller Univ, Aaron Diamond AIDS Res Ctr, 455 1st Ave, New York, NY 10016 USA. EM lzhang@adarc.org FU NCRR NIH HHS [R01 RR006555, RR06555]; NIAID NIH HHS [AI28433, AI42669, AI46964, R01 AI028433, R01 AI046964, R37 AI028433] NR 29 TC 62 Z9 62 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 27 PY 2007 VL 104 IS 48 BP 19079 EP 19084 DI 10.1073/pnas.0707449104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 239DK UT WOS:000251498700040 PM 18025463 ER PT J AU Welch, HG Woloshin, S Schwartz, LM Gordis, L Gotzsche, PC Harris, R Kramer, BS Ransohoff, DF AF Welch, H. Gilbert Woloshin, Steven Schwartz, Lisa M. Gordis, Leon Gotzsche, Peter C. Harris, Russell Kramer, Barnett S. Ransohoff, David F. TI Overstating the evidence for lung cancer screening - The international early lung cancer action program (I-ELCAP) study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID NEEDLE ASPIRATION BIOPSY; COMPUTED-TOMOGRAPHY SCANNER; FOLLOW-UP; BREAST-CANCER; PNEUMOTHORAX RATE; TRIAL; OVERDIAGNOSIS; SURVIVAL; PROJECT; RISK AB Last year, the New England Journal of Medicine ran a lead article reporting that patients with lung cancer had a 10-year survival approaching 90% if detected by screening spiral computed tomography. The publication garnered considerable media attention, and some felt that its findings provided a persuasive case for the immediate initiation of lung cancer screening. We strongly disagree. In this article, we highlight 4 reasons why the publication does not make a persuasive case for screening: the study had no control group, it lacked an unbiased outcome measure, it did not consider what is already known about this topic from previous studies, and it did not address the harms of screening. We conclude with 2 fundamental principles that physicians should remember when thinking about screening: (1) survival is always, prolonged by early detection, even when deaths are not delayed nor any lives saved, and (2) randomized trials are the only way to reliably determine whether screening does more good than harm. C1 White River Junct VA Med Ctr, VA Outcomes Grp, Hanover, NH USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. Rigshosp, Nordic Cochrane Ctr, Copenhagen, Denmark. Univ N Carolina, Sch Med, Chapel Hill, NC 27515 USA. Natl Inst Hlth, Off Dis Prevent, Bethesda, MD USA. RP Schwartz, LM (reprint author), White River Junct VA Med Ctr, VA Outcomes Grp, 215 N Main St,11B, Hanover, NH USA. EM lisa.schwartz@dartmouth.edu NR 49 TC 45 Z9 47 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 26 PY 2007 VL 167 IS 21 BP 2289 EP 2295 DI 10.1001/archinte.167.21.2289 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 235EU UT WOS:000251217100003 PM 18039986 ER PT J AU Eskandari, F Martinez, PE Torvik, S Phillips, TM Sternberg, EM Mistry, S Ronsaville, D Wesley, R Toomey, C Sebring, NG Reynolds, JC Blackman, MR Calis, KA Gold, PW Cizza, G AF Eskandari, Farideh Martinez, Pedro E. Torvik, Sara Phillips, Terry M. Sternberg, Esther M. Mistry, Sejal Ronsaville, Donna Wesley, Robert Toomey, Caitlin Sebring, Nancy G. Reynolds, James C. Blackman, Marc R. Calis, Karim A. Gold, Philip W. Cizza, Giovanni CA POWER Study Grp TI Low bone mass in premenopausal women with depression SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID EARLY POSTMENOPAUSAL WOMEN; MINERAL DENSITY; MAJOR DEPRESSION; RISK-FACTOR; DISORDER; OSTEOPOROSIS; MENOPAUSE; PLASMA; CYTOKINES; MARKERS AB Background: An increased prevalence of low bone mineral density (BMD) has been reported in patients with major depressive disorder (MDD), mostly women. Methods: Study recruitment was conducted from July 1, 2001, to February 29, 2003. We report baseline BMD measurements in 89 premenopausal women with MDD and 44 healthy control women enrolled in a prospective study of bone turnover. The BMD was measured by dual-energy x-ray absorptiometry at the spine, hip, and forearm. Mean hourly levels of plasma 24-hour cytokines, 24-hour urinary free cortisol, and catecholamine excretion were measured in a subset of women. We defined MDD according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Results: The prevalence of low BMD, defined as a T score of less than -1, was greater in women with MDD vs controls at the femoral neck (17% vs 2%; P=.02) and total hip (15% vs 2%; P=.03) and tended to be greater at the lumbar spine (20% vs 9%; P=.14). The mean +/- SD BMD, expressed as grams per square centimeters, was lower in women with MDD at the femoral neck (0.849 +/- 0.121 vs 0.866 +/- 0.094; P=.05) and at the lumbar spine (1.024 +/- 0.117 vs 1.043 +/- 0.092; P=.05) and tended to be lower at the radius (0.696 +/- 0.049 vs 0.710 +/- 0.055; P=.07). Women with MDD had increased mean levels of 24-hour proinflammatory cytokines and decreased levels of anti-inflammatory cytokines. Conclusions: Low BMD is more prevalent in premenopausal women with MDD. The BMD deficits are of clinical significance and comparable in magnitude to those resulting from established risk factors for osteoporosis, such as smoking and reduced calcium intake. The possible contribution of immune or inflammatory imbalance to low BMD in premenopausal women with MDD remains to be clarified. C1 Case Western Reserve Univ, Dept Med, Div Clin & Mol Endocrinol, Cleveland, OH USA. Sect Neuroendocrine Immunol, Behav Integrat Neural Program, Bethesda, MD USA. Clin Neuroendocrinol Branch, Bethesda, MD USA. Behav Endocrinol Branch, Bethesda, MD USA. NIDDK, NIMH, Clin Endocrinol Branch, Bethesda, MD USA. Dept & Clin Epidemiol Serv, Bethesda, MD USA. Dept Nutr, Bethesda, MD USA. Dept Nucl Med, Bethesda, MD USA. Dept Pharm, Drug Informat Serv, Bethesda, MD USA. Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD USA. Natl Ctr Complementary & Alternative Med, Clin Invest Lab, Endocrinol Sect, Bethesda, MD USA. Mark O Hatfield Clin Res Ctr, Bethesda, MD USA. Natl Inst Hlth, Bethesda, MD USA. RP Cizza, G (reprint author), Clin Res Ctr, Bldg 10,Room 6-3940, Bethesda, MD 20892 USA. EM cizzag@intra.niddk.nih.gov FU Intramural NIH HHS NR 35 TC 89 Z9 94 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 26 PY 2007 VL 167 IS 21 BP 2329 EP 2336 DI 10.1001/archinte.167.21.2329 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 235EU UT WOS:000251217100009 PM 18039992 ER PT J AU Guo, XM Chen, KH Guo, YH Liao, H Tang, J Xiao, RP AF Guo, Xiaomei Chen, Kuang-Hueih Guo, Yanhong Liao, Hua Tang, Jian Xiao, Rui-Ping TI Mitofusin 2 triggers vascular smooth muscle cell apoptosis via mitochondrial death pathway SO CIRCULATION RESEARCH LA English DT Article DE PI3K-Akt; apoptosis; HSG; Mfn-2; vascular smooth muscle cells ID IN-VIVO; RAS; PROLIFERATION; INHIBITION; ANGIOPLASTY; PROTEINS; RESTENOSIS; SURVIVAL; BINDING; CANCER AB Previous studies have shown that mitofusin 2 (Mfn-2) (or hyperplasia suppressor gene [HSG]) inhibits vascular smooth muscle cell (VSMC) proliferation. Here, we demonstrate that Mfn-2 is a primary determinant of VSMC apoptosis. First, oxidative stress with H2O2, inhibition of protein kinase C with staurosporine, activation of protein kinase A with forskolin, and serum deprivation concurrently elevate Mfn-2 expression and induce VSMC apoptosis. Second, overexpression of Mfn-2 also triggers apoptosis of VSMCs in culture and in balloon- injured rat carotid arteries, thus contributing to Mfn-2-mediated prevention of neointima formation after angioplasty. Third, Mfn-2 silencing protects VSMCs against H2O2 or Mfn-2 overexpression-induced apoptosis, indicating that upregulation of Mfn-2 is necessary and sufficient for oxidative stress-mediated VSMC apoptosis. The Mfn-2 proapoptotic effect is independent of its role in mitochondrial fusion but mainly mediated by inhibition of Akt signaling and the resultant activation of the mitochondrial apoptotic pathway, as manifested by decreased Akt phosphorylation, increased mitochondrial Bax/Bcl-2 ratio, cytochrome c release, and activation of caspases-9 and caspase-3. Furthermore, Mfn-2-induced apoptosis was blocked by overexpression of an active phosphoinositide 3-kinase mutant or Bcl-xL or inhibition of caspase-9 but not caspases-8. Thus, in addition to its antiproliferative effects, Mfn-2 constitutes a primary determinant of VSMC apoptosis. C1 NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. Peking Univ, Inst Cardiovasc Sci, Beijing 100871, Peoples R China. Huazhong Univ Sci & Technol, Tongji Med Coll, Ctr Mol Cardiol, Tongji Hosp,Dept Cardiol, Wuhan 430074, Peoples R China. RP Chen, KH (reprint author), NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM chenku@grc.nia.nih.gov RI GUO, Yanhong/B-5325-2012; Guo, Yanhong/D-9764-2012 FU Intramural NIH HHS NR 40 TC 87 Z9 114 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV 26 PY 2007 VL 101 IS 11 BP 1113 EP 1122 DI 10.1161/CIRCRESAHA.107.157644 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 235HS UT WOS:000251225000009 PM 17901359 ER PT J AU Sun, JH Morgan, M Shen, RF Steenbergen, C Murphy, E AF Sun, Junhui Morgan, Meghan Shen, Rong-Fong Steenbergen, Charles Murphy, Elizabeth TI Preconditioning results in S-nitrosylation of proteins involved in regulation of mitochondrial energetics and calcium transport SO CIRCULATION RESEARCH LA English DT Article DE preconditioning; S-nitrosylation; cardioprotection ID K-ATP CHANNELS; NITRIC-OXIDE; SARCOPLASMIC-RETICULUM; CARDIOVASCULAR-SYSTEM; MYOCARDIAL-ISCHEMIA; RAT HEARTS; COMPLEX-I; INJURY; CARDIOPROTECTION; GLUTATHIOLATION AB Nitric oxide has been shown to be an important signaling messenger in ischemic preconditioning (IPC). Accordingly, we investigated whether protein S-nitrosylation occurs in IPC hearts and whether S-nitrosoglutathione (GSNO) elicits similar effects on S-nitrosylation and cardioprotection. Preceding 20 minutes of no-flow ischemia and reperfusion, hearts from C57BL/6J mice were perfused in the Langendorff mode and subjected to the following conditions: (1) control perfusion; (2) IPC; or (3) 0.1 mmol/L GSNO treatment. Compared with control, IPC and GSNO significantly improved postischemic recovery of left ventricular developed pressure and reduced infarct size. IPC and GSNO both significantly increased S-nitrosothiol contents and S-nitrosylation levels of the L-type Ca2(+) channel alpha 1 subunit in heart membrane fractions. We identified several candidate S-nitrosylated proteins by proteomic analysis following the biotin switch method, including the cardiac sarcoplasmic reticulum Ca2(+)-ATPase, alpha-ketoglutarate dehydrogenase, and the mitochondrial F1-ATPase alpha 1 subunit. The activities of these enzymes were altered in a concentration-dependent manner by GSNO treatment. We further developed a 2D DyLight fluorescence difference gel electrophoresis proteomic method that used DyLight fluors and a modified biotin switch method to identify S-nitrosylated proteins. IPC and GSNO produced a similar pattern of S-nitrosylation modification and cardiac protection against ischemia/reperfusion injury, suggesting that protein S-nitrosylation may play an important cardioprotective role in heart. C1 NHLBI, NIH, Vasc Med Branch, Bethesda, MD 20892 USA. NHLBI, NIH, Proteom Core Facil, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. RP Murphy, E (reprint author), NHLBI, NIH, Vasc Med Branch, Room 7N112,Bldg 10,Magnuson CC,10 Ctr Dr, Bethesda, MD 20892 USA. EM murphy1@mail.nih.gov RI Sun, Junhui/C-3499-2011 FU Intramural NIH HHS; NHLBI NIH HHS [HL-39752, R01 HL039752] NR 44 TC 227 Z9 233 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV 26 PY 2007 VL 101 IS 11 BP 1155 EP 1163 DI 10.1161/CIRCRESAHA.107.155879 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 235HS UT WOS:000251225000014 PM 17916778 ER PT J AU Najjar, SS Willer, CJ Sanna, S Jackson, AU Scuteri, A Clarke, R Galan, P Meneton, P Zelenika, D Sundvall, J Watanabe, RM Shuldiner, AR Collins, R Bergman, RN Uda, M Tuomilehto, J Collins, FS Lathrop, GM Boehnke, M Schlessinger, D Abecasis, GR Cao, A Mohlke, KL Lakatta, EG AF Najjar, Samer S. Willer, Cristen J. Sanna, Serena Jackson, Anne U. Scuteri, Angelo Clarke, Robert Galan, Pilar Meneton, Pierre Zelenika, Diana Sundvall, Jouko Watanabe, Richard M. Shuldiner, Alan R. Collins, Rory Bergman, Richard N. Uda, Manuela Tuomilehto, Jaakko Collins, Francis S. Lathrop, G. M. Boehnke, Michael Schlessinger, David Abecasis, Goncalo R. Cao, Antonio Mohlke, Karen L. Lakatta, Edward G. TI Genome-wide association scans identify novel loci that influence lipid levels and risk of coronary artery disease SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association (AHA) CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc (AHA) C1 NIH, NIA, Baltimore, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Oxford, Oxford, England. Fac Med Rene Descartes, Paris, France. INSERM, U557, Bobigny, France. Cntr Natl Genotypage, Evry, France. Natl Publ Hlth Inst, Helsinki, Finland. Univ So Calif, Los Angeles, CA USA. Univ Maryland, Baltimore, MD 21201 USA. Cittadella Univ Monserrato, Cagliari, Italy. Univ Helsinki, Helsinki, Finland. NHGRI, Bethesda, MD 20892 USA. NIH, NIA, Cntr Natl Genotypage, Baltimore, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD NOV 26 PY 2007 VL 101 IS 11 MA 4010 BP 1207 EP 1207 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 235HS UT WOS:000251225000030 ER PT J AU Kovalchuk, AL Dubois, W Mushinski, E McNeil, NE Hirt, C Qi, CF Li, ZY Janz, S Honjo, T Muramatsu, M Ried, T Behrens, T Potter, M AF Kovalchuk, Alexander L. Dubois, Wendy Mushinski, Elizabeth McNeil, Nicole E. Hirt, Carsten Qi, Chen-Feng Li, Zhaoyang Janz, Siegfried Honjo, Tasuku Muramatsu, Masamichi Ried, Thomas Behrens, Timothy Potter, Michael TI AID-deficient Bcl-xL transgenic mice develop delayed atypical plasma cell tumors with unusual Ig/Myc chromosomal rearrangements SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION; DOUBLE-STRAND BREAKS; WILD-TYPE P53; C-MYC; DNA-DAMAGE; GENE AMPLIFICATION; MURINE PLASMACYTOMA; MOUSE PLASMACYTOMA; B-CELLS AB Activation-induced cytidine deaminase (AID) is required for immunoglobulin (Ig) class switch recombination and somatic hypermutation, and has also been implicated in translocations between Ig switch regions and c-Myc in plasma cell tumors in mice. We asked if AID is required for accelerated tumor development in pristane-treated Bcl-xL transgenic BALB/c mice deficient in AID (pBxAicda-/-). pBxAicda-/- mice developed tumors with a lower frequency (24 vs. 62%) and a longer mean latency (108 vs. 36 d) than AID-sufficient mice. The tumors appeared in oil granuloma tissue and did not form ascites. By interphase fluorescence in situ hybridization, six out of nine pBx Aicda-/- primary tumors had T(12; 15) and one had T(6; 15) chromosomal translocations. Two tumors were transplantable and established as stable cell lines. Molecular and cytogenetic analyses showed that one had an unusual unbalanced T(12; 15) translocation, with IgH C mu and Pvt-1 oriented head to tail at the breakpoint, resulting in an elevated expression of c-Myc. In contrast, the second was T(12; 15) negative, but had an elevated N-Myc expression caused by a paracentric inversion of chromosome 12. Thus, novel mechanisms juxtapose Ig and Myc-family genes in AID-deficient plasma cell tumors. C1 Natl Inst Hlth, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. Natl Inst Hlth, Natl Canc Inst, Canc Genom Sect, Genet Branch, Bethesda, MD 20892 USA. Ernst Moritz Arndt Univ Greifswald, D-17487 Greifswald, Germany. Natl Inst Hlth, NIAID, Immunopathol Lab, Rockville, MD 20852 USA. Univ Iowa, Carver Roy J & Lucille A Carver Coll Med, Dept Pathol, Iowa City, IA 52242 USA. Kyoto Univ, Grad Sch Med, Dept Immunol & Genom Med, Kyoto 6068501, Japan. Kanazawa Univ, Grad Sch Med Sci, Dept Mol Genet, Kanazawa, Ishikawa 9208640, Japan. Genentech Inc, San Francisco, CA 94080 USA. RP Potter, M (reprint author), Natl Inst Hlth, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. EM potter@helix.nih.gov RI Muramatsu, Masamichi/C-4339-2015; Honjo, Tasuku/N-4470-2016 OI Muramatsu, Masamichi/0000-0002-0153-3533; FU Intramural NIH HHS NR 70 TC 32 Z9 33 U1 0 U2 1 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 NOV 26 PY 2007 VL 204 IS 12 BP 2989 EP 3001 DI 10.1084/jem.20070882 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 236RE UT WOS:000251320300022 PM 17998390 ER PT J AU Albu, DI Feng, DY Bhattacharya, D Jenkins, NA Copeland, NG Liu, PT Avram, D AF Albu, Diana I. Feng, Dongyun Bhattacharya, Debarati Jenkins, Nancy A. Copeland, Neal G. Liu, Pentao Avram, Dorina TI BCL11B is required for positive selection and survival of double-positive thymocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL DEVELOPMENT; NEGATIVE SELECTION; LINEAGE COMMITMENT; CD4+8+ THYMOCYTES; TRANSGENIC MICE; EXPRESSION; DIFFERENTIATION; ACTIVATION; GENE; LYMPHOCYTES AB Transcriptional control of gene expression in double-positive (DP) thymocytes remains poorly understood. We show that the transcription factor BCL11B plays a critical role in DP thymocytes by controlling positive selection of both CD4 and CD8 lineages. BCL11B-deficient DP thymocytes rearrange T cell receptor (TCR) alpha; however, they display impaired proximal TCR signaling and attenuated extracellular signal-regulated kinase phosphorylation and calcium flux, which are all required for initiation of positive selection. Further, provision of transgenic TCRs did not improve positive selection of BCL11B-deficient DP thymocytes. BCL11B-deficient DP thymocytes have altered expression of genes with a role in positive selection, TCR signaling, and other signaling pathways intersecting the TCR, which may account for the defect. BCL11B-deficient DP thymocytes also presented increased susceptibility to spontaneous apoptosis associated with high levels of cleaved caspase-3 and an altered balance of proapoptotic/prosurvival factors. This latter susceptibility was manifested even in the absence of TCR signaling and was only partially rescued by provision of the BCL2 transgene, indicating that control of DP thymocyte survival by BCL11B is nonredundant and, at least in part, independent of BCL2 prosurvival factors. C1 Albany Med Coll, Ctr Cell Biol & Canc Res, Albany, NY 12208 USA. Natl Inst Hlth, Natl Canc Inst, Mouse Canc Genet Program, Frederick, MD 21702 USA. Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. RP Avram, D (reprint author), Albany Med Coll, Ctr Cell Biol & Canc Res, Albany, NY 12208 USA. EM avramd@mail.amc.edu FU NHLBI NIH HHS [T32-HL-07194, T32 HL007194]; NIAID NIH HHS [R01 AI067846, R01 AI067846-01A2]; NIAMS NIH HHS [K01 AR-02194, K01 AR002194] NR 63 TC 70 Z9 71 U1 1 U2 5 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 NOV 26 PY 2007 VL 204 IS 12 BP 3003 EP 3015 DI 10.1084/jem.20070863 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 236RE UT WOS:000251320300023 PM 17998389 ER PT J AU Marzi, A Mitchell, DA Chaipan, C Fisch, T Doms, RW Carrington, M Desrosiers, RC Pohlmann, S AF Marzi, Andrea Mitchell, Daniel A. Chaipan, Chawaree Fisch, Tanja Doms, Robert W. Carrington, Mary Desrosiers, Ronald C. Poehlmann, Stefan TI Modulation of HIV and SIV neutralization sensitivity by DC-SIGN and mannose-binding lectin SO VIROLOGY LA English DT Article DE SIV; DC-SIGN; MBL; neutralization; attachment; antibody ID HUMAN-IMMUNODEFICIENCY-VIRUS; C-TYPE LECTIN; ADHESION MOLECULE-3-GRABBING NONINTEGRIN; DENDRITIC CELLS; T-CELLS; ENDOTHELIAL-CELLS; RHESUS MACAQUE; MEDIATED INTERNALIZATION; MONOCLONAL-ANTIBODIES; ANTIGEN PRESENTATION AB The C-type lectin DC-SIGN binds to oligosaccharides on the human and simian immunodeficiency virus (HIV, SIV) envelope glycoproteins and promotes infection of susceptible cells. Here, we show that DC-SIGN recognizes glycans involved in SIV sensitivity to neutralizing antibodies and that binding to DC-SIGN confers neutralization resistance to an otherwise sensitive SIV variant. Moreover, we provide evidence that mannosebinding lectin (MBL) can interfere with HIV-1 neutralization by the carbohydrate-specific antibody 2GI2. (c) 2007 Elsevier Inc. All rights reserved. C1 Hannover Med Sch, Inst Virol, D-30625 Hannover, Germany. Univ Hosp Erlangen, Inst Clin & Mol Virol, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, D-91054 Erlangen, Germany. Warwick Med Sch, Clin Sci Res Inst, Coventry CV2 2DX, W Midlands, England. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. SAIC Frederick Inc, NCI, Lab Genom Divers, Ft Detrick, MD 21702 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. RP Pohlmann, S (reprint author), Hannover Med Sch, Inst Virol, OE 5230,Carl Neuberg Str 1, D-30625 Hannover, Germany. EM poehlmann.stefan@mh-harinover.de RI Mitchell, Daniel/A-6580-2009; OI Mitchell, Daniel/0000-0003-0936-6212; Pohlmann, Stefan/0000-0001-6086-9136 FU NCI NIH HHS [N01-CO-12400] NR 63 TC 17 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 0042-6822 J9 VIROLOGY JI Virology PD NOV 25 PY 2007 VL 368 IS 2 BP 322 EP 330 DI 10.1016/j.virol.2007.07.004 PG 9 WC Virology SC Virology GA 230QQ UT WOS:000250891400012 PM 17659761 ER PT J AU Su, HP Golden, JW Gittis, AG Hooper, JW Garboczi, DN AF Su, Hua-Poo Golden, Joseph W. Gittis, Apostolos G. Hooper, Jay W. Garboczi, David N. TI Structural basis for the binding of the neutralizing antibody, 7D11, to the poxvirus L1 protein SO VIROLOGY LA English DT Article DE conformational epitope; vaccinia; poxvirus L1R; neutralizing antibody; fab structure ID VACCINIA VIRUS L1R; MEMBRANE-PROTEIN; SMALLPOX VACCINE; MONOCLONAL-ANTIBODIES; PENETRATION PROTEIN; NONHUMAN-PRIMATES; DISULFIDE BRIDGES; MICE; CHALLENGE; PROTECTION AB Medical countermeasures to prevent or treat smallpox are needed due to the potential use of poxviruses as biological weapons. Safety concerns with the currently available smallpox vaccine indicate a need for research on alternative poxvirus vaccine strategies. Molecular vaccines involving the use of proteins and/or genes and recombinant antibodies are among the strategies under current investigation. The poxvirus L I protein, encoded by the L I R open reading frame, is the target of neutralizing antibodies and has been successfully used as a component of both protein subunit and DNA vaccines. L1-specific monoclonal antibodies (e.g., mouse monoclonal antibody mAb-7D 11, mAb- 10F5) with potent neutralizing activity bind L I in a conformation -specific manner. This suggests that proper folding of the L1 protein used in molecular vaccines will affect the production of neutralizing antibodies and protection. Here, we co-crystallized the Fab fragment of mAb-7D11 with the L1 protein. The crystal structure of the complex between Fab-7D11 and L1 reveals the basis for the conformation-specific binding as recognition of a discontinuous epitope containing two loops that are held together by a disulfide bond. The structure of this important conformational epitope of L I will contribute to the development of molecular poxvirus vaccines and also provides a novel target for anti-poxvirus drugs. In addition, the sequence and structure of Fab-7D11 will contribute to the development of L1-targeted immunotherapeutics. Published by Elsevier Inc. C1 NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. RP Garboczi, DN (reprint author), NIAID, Struct Biol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM dgarboczi@niaid.nih.gov OI Hooper, Jay/0000-0002-4475-0415 FU Intramural NIH HHS [Z01 AI000956-03] NR 47 TC 23 Z9 24 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 25 PY 2007 VL 368 IS 2 BP 331 EP 341 DI 10.1016/j.virol.2007.06.042 PG 11 WC Virology SC Virology GA 230QQ UT WOS:000250891400013 PM 17688903 ER PT J AU Sundaravaradan, V Das, SR Ramakrishnan, R Sehgal, S Gopalan, S Ahmad, N Jameel, S AF Sundaravaradan, Vasudha Das, Suman R. Ramakrishnan, Rajesh Sehgal, Shobha Gopalan, Sarla Ahmad, Nafees Jameel, Shahid TI Role of HIV-I subtype C envelope V3 to V5 regions in viral entry, coreceptor utilization and replication efficiency in primary T-lymphocytes and monocyte-derived macrophages SO VIROLOGY JOURNAL LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; V3 LOOP; PERINATAL TRANSMISSION; NEUTRALIZING ANTIBODY; SYNCYTIUM FORMATION; GENETIC-ANALYSIS; CELL TROPISM; TYPE-1; INDIA; IDENTIFICATION AB Background: Several subtypes of HIV-I circulate in infected people worldwide, including subtype B in the United States and subtype C in Africa and India. To understand the biological properties of HIV-I subtype C, including cellular tropism, virus entry, replication efficiency and cytopathic effects, we reciprocally inserted our previously characterized envelope V3-V5 regions derived from 9 subtype C infected patients from India into a subtype B molecular clone, pNL4-3. Equal amounts of the chimeric viruses were used to infect T-lymphocyte cell lines (A3.01 and MT-2), coreceptor cell lines (U373-MAGI-CCR5/CXCR4), primary blood T-lymphocytes (PBL) and monocyte-derived macrophages (MDM). Results: We found that subtype C envelope V3-V5 region chimeras failed to replicate in T-lymphocyte cell lines but replicated in PBL and MDM. In addition, these chimeras were able to infect U373MAGI-CD4(+)-CCR5(+) but not U373MAGI-CD4(+)-CXCR4(+) cell line, suggesting CCR5 coreceptor utilization and R5 phenotypes. These subtype C chimeras were unable to induce syncytia in MT-2 cells, indicative of non-syncytium inducing (NSI) phenotypes. More importantly, the subtype C envelope chimeras replicated at higher levels in PBL and MDM compared with subtype B chimeras and isolates. Furthermore, the higher levels subtype C chimeras replication in PBL and MDM correlated with increased virus entry in U373MAGI-CD4(+)-CCR5(+). Conclusion: Taken together, these results suggest that the envelope V3 to V5 regions of subtype C contributed to higher levels of HIV-I replication compared with subtype B chimeras, which may contribute to higher viral loads and faster disease progression in subtype C infected individuals than other subtypes as well as rapid HIV-I subtype C spread in India. C1 [Sundaravaradan, Vasudha; Ramakrishnan, Rajesh; Ahmad, Nafees] Univ Arizona, Coll Med, Dept Immunobiol, Tucson, AZ 85724 USA. [Das, Suman R.; Jameel, Shahid] Int Ctr Genet Engn & Biotechnol, Virol Grp, New Delhi, India. [Sehgal, Shobha; Gopalan, Sarla] Post Grad Inst Med Educ & Res, Dept Pathol, Chandigarh, India. [Sehgal, Shobha; Gopalan, Sarla] Post Grad Inst Med Educ & Res, Dept Obstet & Ginecol, Chandigarh, India. [Das, Suman R.] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. [Ramakrishnan, Rajesh] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Ahmad, N (reprint author), Univ Arizona, Coll Med, Dept Immunobiol, Tucson, AZ 85724 USA. EM vsvaradan@yahoo.com; dassr@niaid.nih.gov; ramakris@bcm.tmc.edu; sehgal@hotmail.com; Gopalan@hotmail.com; nafees@u.arizona.edu; jameelshahid@gmail.com RI Das, Suman/C-8760-2009 FU FIC NIH HHS [R03 TW001345, TW 01345]; NIAID NIH HHS [AI 40378, R21 AI040378] NR 51 TC 12 Z9 14 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD NOV 24 PY 2007 VL 4 AR 126 DI 10.1186/1743-422X-4-126 PG 12 WC Virology SC Virology GA 255JW UT WOS:000252655300001 PM 18036244 ER PT J AU Das, S Ise, T Nagata, S Maeda, H Bera, TK Pastan, I AF Das, Sudipto Ise, Tomoko Nagata, Satoshi Maeda, Hiroshi Bera, Tapan K. Pastan, Ira TI Palmitoylation of POTE family proteins for plasma membrane targeting SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE prostate; evolution; protein modification; plasma membrane; palmitoylation; S-acylation; subcellular localization; spectrin; ankyrin ID SIGNALING PROTEINS; ANKYRIN REPEAT; LOCALIZATION; PREDICTION; ACYLATION; PROSTATE; PARALOGS; PALM AB The POTE gene family is composed of 13 paralogs and likely evolved by duplications and remodeling of the human genome. One common property of POTE proteins is their localization on the inner aspect of the plasma membrane. To determine the structural elements required for membrane localization, we expressed mutants of different POTEs in 293T cells as EGFP fusion proteins. We also tested their palmitoylation by a biotin-switch assay. Our data indicate that the membrane localizations of different POTEs are mediated by similar 3-4 short cysteine rich repeats (CRRs) near the amino-terminuses and that palmitoylation on paired cysteine residues in each CRR motif is responsible for the localization. Multiple palmitoylation in the small CRRs can result in the strong association of whole POTEs with plasma membrane. Published by Elsevier Inc. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov FU Intramural NIH HHS [Z01 BC010298-09] NR 27 TC 4 Z9 5 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 23 PY 2007 VL 363 IS 3 BP 751 EP 756 DI 10.1016/j.bbrc.2007.09.045 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 223HA UT WOS:000250359400050 PM 17904529 ER PT J AU Le Stunff, H Giussani, P Maceyka, M Lepine, S Milstien, S Spiegel, S AF Le Stunff, Herve Giussani, Paola Maceyka, Michael Lepine, Sandrine Milstien, Sheldon Spiegel, Sarah TI Recycling of sphingosine is regulated by the concerted actions of sphingosine-1-phosphate phosphohydrolase 1 and sphingosine kinase 2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIPID PHOSPHATE PHOSPHATASES; EPIDERMAL-GROWTH-FACTOR; SPHINGOLIPID METABOLISM; GLUCOSYLCERAMIDE SYNTHASE; SACCHAROMYCES-CEREVISIAE; CERAMIDE GENERATION; MAMMALIAN-CELLS; KEY REGULATOR; RAT-LIVER; DE-NOVO AB In yeast, the long-chain sphingoid base phosphate phosphohydrolase Lcb3p is required for efficient ceramide synthesis from exogenous sphingoid bases. Similarly, in this study, we found that incorporation of exogenous sphingosine into ceramide in mammalian cells was regulated by the homologue of Lcb3p, sphingosine-1-phosphate phosphohydrolase 1 (SPP-1), an endoplasmic reticulum resident protein. Sphingosine incorporation into endogenous long-chain ceramides was increased by SPP-1 overexpression, whereas recycling of C-6-ceramide into long-chain ceramides was not altered. The increase in ceramide was inhibited by fumonisin B-1, an inhibitor of ceramide synthase, but not by ISP-1, an inhibitor of serine palmitoyltransferase, the rate-limiting step in the de novo biosynthesis of ceramide. Mass spectrometry analysis revealed that SPP-1 expression increased the incorporation of sphingosine into all ceramide acyl chain species, particularly enhancing C16:0, C18:0, and C20:0 long-chain ceramides. The increased recycling of sphingosine into ceramide was accompanied by increased hexosylceramides and, to a lesser extent, sphingomyelins. Sphingosine kinase 2, but not sphingosine kinase 1, acted in concert with SPP-1 to regulate recycling of sphingosine into ceramide. Collectively, our results suggest that an evolutionarily conserved cycle of phosphorylation-dephosphorylation regulates recycling and salvage of sphingosine to ceramide and more complex sphingolipids. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM sspiegel@vcu.edu RI Maceyka, Michael/B-9277-2008 FU Intramural NIH HHS; NIGMS NIH HHS [GM 069338, GM 43880] NR 52 TC 44 Z9 48 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 NOV 23 PY 2007 VL 282 IS 47 BP 34372 EP 34380 DI 10.1074/jbc.M703329200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 234FI UT WOS:000251145700053 PM 17895250 ER PT J AU Martin, MJ Tanos, T Garcia, AB Martin, D Gutkind, JS Coso, OA Marinissen, MJ AF Martin, Maria Jose Tanos, Tamara Garcia, Ana Belen Martin, Daniel Gutkind, J. Silvio Coso, Omar A. Marinissen, Maria Julia TI The G alpha(12/13) family of heterotrimeric G proteins and the small GTPase RhoA link the Kaposi Sarcoma-associated herpes virus G protein-coupled receptor to heme oxygenase-1 expression and tumorigenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; LEUKEMIA-ASSOCIATED RHO; RENAL-CELL CARCINOMA; SMOOTH-MUSCLE-CELLS; FACTOR-KAPPA-B; GENE-EXPRESSION; UP-REGULATION; CANCER CELLS; IN-VITRO; NEONATAL HYPERBILIRUBINEMIA AB Heme oxygenase-1 (HO-1), an inducible enzyme that metabolizes the heme group, is highly expressed in human Kaposi sarcoma lesions. Its expression is up-regulated by the G protein-coupled receptor from the Kaposi sarcoma-associated herpes virus (vGPCR). Although recent evidence shows that HO-1 contributes to vGPCR-induced tumorigenesis and vascular endothelial growth factor (VEGF) expression, the molecular steps that link vGPCR to HO-1 remain unknown. Here we show that vGPCR induces HO-1 expression and transformation through the G alpha(12/13) family of heterotrimeric G proteins and the small GTPase RhoA. Targeted small hairpin RNA knockdown expression of G alpha(12), G alpha(13), or RhoA and inhibition of RhoA activity impair vGPCR- induced transformation and ho-1 promoter activity. Knockdown expression of RhoA also reduces vGPCR-induced VEFG-A secretion and blocks tumor growth in a murine allograft tumor model. NIH-3T3 cells expressing constitutively activated G alpha(13) or RhoA implanted in nude mice develop tumors displaying spindle-shaped cells that express HO-1 and VEGF-A, similarly to vGPCR-derived tumors. RhoAQL-induced tumor growth is reduced 80% by small hairpin RNA-mediated knockdown expression of HO-1 in the implanted cells. Likewise, inhibition of HO-1 activity by chronic administration of the HO-1 inhibitor tin protoporphyrin IX to mice reduces RhoAQL-induced tumor growth by 70%. Our study shows that vGPCR induces HO-1 expression through the G alpha(12/13)/RhoA axes and shows for the first time a potential role for HO-1 as a therapeutic target in tumors where RhoA has oncogenic activity. C1 Univ Autonoma Madrid, Fac Med, Dept Bioquim, Inst Invest Biomed A Sols, E-28029 Madrid, Spain. Univ Buenos Aires, IFYBYNE CONICET, Fac Ciencias Exactas & Nat, Dept Fisiol & Biol Mol, RA-1428 Buenos Aires, DF, Argentina. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Marinissen, MJ (reprint author), Univ Autonoma Madrid, Fac Med, Dept Bioquim, Inst Invest Biomed A Sols, Arzobispo Morcillo 4, E-28029 Madrid, Spain. EM mjmarinissen@iib.uam.es RI Gutkind, J. Silvio/A-1053-2009; Martin, Maria Jose/E-5105-2011; OI Martin, Maria Jose/0000-0002-0202-7309; Martin, Maria Jose/0000-0001-6988-0761 NR 89 TC 13 Z9 15 U1 1 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 NOV 23 PY 2007 VL 282 IS 47 BP 34510 EP 34524 DI 10.1074/jbc.M703043200 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 234FI UT WOS:000251145700066 PM 17881360 ER PT J AU Ito, Y Clary, R Sharpnak, F Metger, H Powell, J AF Ito, Yoichiro Clary, Robert Sharpnak, Frank Metger, Howard Powell, Jimmie TI Mixer-settler counter-current chromatography with multiple spiral disk assembly SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE mixer-settler counter-current chromatography; barricaded spiral channel; polymer phase system; lysozyme; myoglobin AB A novel system for performing high-speed counter-current chromatography has been developed for separation of biopolymers using polymer phase systems. The spiral disk assembly consisting of eight units, each equipped with over 300 mixer-settler sets, was constructed and performance evaluated in terms of retention of the stationary phase and separation efficiency. A series of experiments was performed with a polymer phase system composed of polyethylene glycol 1000 (12.5%, w/w) and dibasic potassium phosphate (12.5%, w/w) using two stable protein samples of myoglobin and lysozyme at various experimental conditions of flow rates and revolution speeds. The best results were obtained with revolution speeds of 800-1000 rpm at flow rates of 0.25-0.5 mi/min where the partition efficiency of several 100 theoretical plates was achieved with over 50% stationary phase retention. Published by Elsevier B.V. C1 NIH, NHLBI, Ctr Biochem & Biophys, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NIH, NHLBI, Ctr Biochem & Biophys, Bldg 50,Room 3334,50 S Dr, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov NR 5 TC 19 Z9 19 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD NOV 23 PY 2007 VL 1172 IS 2 BP 151 EP 159 DI 10.1016/j.chroma.2007.09.078 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 236WY UT WOS:000251335300007 PM 17961580 ER PT J AU Daar, AS Singer, PA Persad, DL Pramming, SK Matthews, DR Beaglehole, R Bernstein, A Borysiewicz, LK Colagiuri, S Ganguly, N Glass, RI Finegood, DT Koplan, J Nabel, EG Sarna, G Sarrafzadegan, N Smith, R Yach, D Bell, J AF Daar, Abdallah S. Singer, Peter A. Persad, Deepa Leah Pramming, Stig K. Matthews, David R. Beaglehole, Robert Bernstein, Alan Borysiewicz, Leszek K. Colagiuri, Stephen Ganguly, Nirmal Glass, Roger I. Finegood, Diane T. Koplan, Jeffrey Nabel, Elizabeth G. Sarna, George Sarrafzadegan, Nizal Smith, Richard Yach, Derek Bell, John TI Grand challenges in chronic non-communicable diseases SO NATURE LA English DT Article ID GLOBAL HEALTH C1 Univ Toronto, Univ Hlth Network, Program Life Sci Eth & Policy, Toronto, ON M5G 1L7, Canada. Oxford Hlth Alliance, London W1W 8RZ, England. Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. Univ Auckland, Fac Med & Hlth Sci, Auckland 1142, New Zealand. Canadian Inst Hlth Res, Ottawa, ON K1A 0W9, Canada. MRC, London W1B 1AL, England. Univ Sydney, Prince Wales Hosp, Ctr Diabet, Randwick, NSW 2031, Australia. Univ Sydney, Prince Wales Hosp, Dept Diabet Endocrinol & Metab, Randwick, NSW 2031, Australia. Indian Council Med Res, New Delhi 110029, India. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Canadian Inst Hlth Res, Inst Nutr Metab & Diabet, Ottawa, ON K1A 0W9, Canada. Emory Univ, Global Hlth Inst, Atlanta, GA 30322 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Isfahan Univ Med Sci, Seddigheh Tahereh Res & Treatment Hosp, Isfahan Cardiovasc Res Ctr, Esfahan, Iran. Unitedhlth Europe, Ovat Chron Dis Initiat, London SW1P 1SB, England. PepsiCo, Purchase, NY 10577 USA. Univ Oxford, John Radcliffe Hosp, Oxford OX3 9DU, England. RP Daar, AS (reprint author), Univ Toronto, Univ Hlth Network, Program Life Sci Eth & Policy, 101 Coll St, Toronto, ON M5G 1L7, Canada. NR 16 TC 283 Z9 292 U1 5 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD NOV 22 PY 2007 VL 450 IS 7169 BP 494 EP 496 DI 10.1038/450494a PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 234JW UT WOS:000251158500032 PM 18033288 ER PT J AU Kim, HJ Hwang, IK Won, MH AF Kim, Hyeon Ju Hwang, In Koo Won, Moo Ho TI Vanillin, 4-hydroxybenzyl aldehyde and 4-hydroxybenzyl alcohol prevent hippocampal CA1 cell death following global ischemia SO BRAIN RESEARCH LA English DT Article DE 4-hydroxybenzyl alcohol; 4-hydoryxybenzyl aldehyde; ischemia; neuroprotection; vanillin ID P-HYDROXYBENZYL ALCOHOL; GASTRODIA-ELATA BLUME; ETHER FRACTION; TRANSIENT ISCHEMIA; METHANOL EXTRACTS; NEURONAL DEATH; MEDICINAL HERB; FREE-RADICALS; BRAIN-INJURY; IN-VIVO AB Mongolian gerbils subjected to transient global ischemia exhibit neuroprotection against ischemic neuronal cell death in the hippocampal CA1 region when treated with vanillin, 4-hydroxybenzyl aldehyde (4-HBAL) and 4-hydroxybenzyl alcohol (4-HBA), which are active components of Gastrodia elata Blume. Pre- and post-insult vanillin, 4-HBAL and 4-HBA treated-animals showed a significant increase in neuronal survival (66.32%, 43.21% and 64.58%, respectively) compared to vehicle-treated animals. Animals exhibited a gender difference in this neuroprotective effect. To study the neuroprotective mechanism of 4-HBA, we investigated N-methyl-D-aspartate (NMDA) receptor 1 (NR1), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and gamma-aminobutyric acid transaminase (GABA-T) immunoreactivity at various times after ischemic insults. Treatment with 4-HBA did not affect NR1 expression levels, down-regulated 8-OHdG immunoreactivity, and increased GABA-T expression levels after global ischemia, suggesting that 4-HBA inhibited NR1 stimulation. Moreover, GABA-T was rapidly increased in the early stage after ischemia, which might enhance the survival of cells by supplying energy to the CA1 region. These results suggest that 4-HBA inhibits oxidative stress and excitotoxicity for at least 12 h and suppresses neuronal death in CA1 region. Diethyl ether fractions of GE scavenged hydroxyl radical (OH) and showed antioxidant activity on lipid peroxidation. Vanillin and 4-HBA treatment blocked oxidative damage in PC12 cells. The neuroprotective effect has therapeutic significance and these compounds need to be evaluated for potential use in protecting against neuronal cell damage during stroke. Published by Elsevier B.V. C1 [Kim, Hyeon Ju] Seoul Natl Univ, Coll Pharm, Dept Pharmacol, Seoul 110799, South Korea. [Hwang, In Koo; Won, Moo Ho] Hallym Univ, Coll Life Sci, Dept Anat, Chunchon 200702, South Korea. RP Kim, HJ (reprint author), NIMH, Mol Neurobiol Sect, NIH, RM 3D-56,10 Ctr Dr,MSC-1363, Bethesda, MD 20892 USA. EM Kimhyunju@mail.nih.gov NR 35 TC 43 Z9 43 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 21 PY 2007 VL 1181 BP 130 EP 141 DI 10.1016/j.brainres.2007.08.066 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 240DR UT WOS:000251567900014 PM 17945203 ER PT J AU Hirota, Y Ohshima, T Kaneko, N Ikeda, M Iwasato, T Kulkarni, AB Mikoshiba, K Okano, H Sawamoto, K AF Hirota, Yuki Ohshima, Toshio Kaneko, Naoko Ikeda, Makiko Iwasato, Takuji Kulkarni, Ashok B. Mikoshiba, Katsuhiko Okano, Hideyuki Sawamoto, Kazunobu TI Cyclin-dependent kinase 5 is required for control of neuroblast migration in the postnatal subventricular zone SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Cdk5; neuroblast; migration; subventricular zone; rostral migratory stream; postnatal neurogenesis ID ADULT MAMMALIAN BRAIN; NEURAL STEM-CELLS; NEURONAL MIGRATION; OLFACTORY-BULB; REGULATORY SUBUNIT; MOUSE FOREBRAIN; CEREBRAL-CORTEX; CDK5; PHOSPHORYLATION; NEUROGENESIS AB At the lateral wall of the lateral ventricles in the adult rodent brain, neuroblasts form an extensive network of elongated cell aggregates called chains in the subventricular zone and migrate toward the olfactory bulb. The molecular mechanisms regulating this migration of neuroblasts are essentially unknown. Here, we report a novel role for cyclin-dependent kinase 5 (Cdk5), a neuronal protein kinase, in this process. Using in vitro and in vivo conditional knock-out experiments, we found that Cdk5 deletion impaired the chain formation, speed, directionality, and leading process extension of the neuroblasts in a cell-autonomous manner. These findings suggest that Cdk5 plays an important role in neuroblast migration in the postnatal subventricular zone. C1 Nagoya City Univ, Grad Sch Med Sci, Inst Mol Med, Dept Dev & Regenerat Biol, Nagoya, Aichi 4678601, Japan. Keio Univ, Sch Med, Bridgestone Lab Dev & Regenerat Neurobiol, Tokyo 1608582, Japan. Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan. Waseda Univ, Dept Life Sci & Med Biosci, Tokyo 1698555, Japan. RIKEN, Brain Sci Inst, Dev Neurobiol Lab, Wako, Saitama 3510198, Japan. RIKEN, Brain Sci Inst, Lab Behav Genet, Wako, Saitama 3510198, Japan. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, Funct Genom Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. Japan Sci & Technol Corp, Solut Oriented Res Sci & Technol, Kawaguchi, Saitama 3320012, Japan. RP Sawamoto, K (reprint author), Nagoya City Univ, Grad Sch Med Sci, Inst Mol Med, Dept Dev & Regenerat Biol, Nagoya, Aichi 4678601, Japan. EM sawamoto@med.nagoya-cu.ac.jp RI Hidokano, Hideyuki/J-5973-2013; Mikoshiba, Katsuhiko/N-7943-2015; OI Sawamoto, Kazunobu/0000-0003-1984-5129 NR 60 TC 42 Z9 47 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 21 PY 2007 VL 27 IS 47 BP 12829 EP 12838 DI 10.1523/JNEUROSCI.1014-07.2007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 234JK UT WOS:000251157200009 PM 18032654 ER PT J AU Gail, MH Anderson, WF Garcia-Closas, M Sherman, ME AF Gail, Mitchell H. Anderson, William F. Garcia-Closas, Montserrat Sherman, Mark E. TI Absolute risk models for subtypes of breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PROGESTERONE-RECEPTOR STATUS; ESTROGEN; VALIDATION C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Gail, MH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Pl S,Room 8032, Bethesda, MD 20892 USA. EM gailm@mail.nih.gov RI Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 NR 13 TC 12 Z9 12 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 NOV 21 PY 2007 VL 99 IS 22 BP 1657 EP 1659 DI 10.1093/jnci/djm228 PG 3 WC Oncology SC Oncology GA 233EA UT WOS:000251072000004 PM 18000214 ER PT J AU Lusa, L McShane, LM Reid, JF De Cecco, L Ambrogi, F Biganzoli, E Gariboldi, M Pierotti, MA AF Lusa, Lara McShane, Lisa M. Reid, James F. De Cecco, Loris Ambrogi, Federico Biganzoli, Elia Gariboldi, Manuela Pierotti, Marco A. TI Challenges in projecting clustering results across gene expression-profiling datasets SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CANCER MOLECULAR SUBTYPES; BREAST-TUMOR SUBTYPES; CLASSIFICATION; SIGNATURE; CARCINOMAS; PORTRAITS; PATTERNS; SURVIVAL; IDENTIFICATION; CHEMOTHERAPY AB Background Gene expression microarray studies for several types of cancer have been reported to identify previously unknown subtypes of tumors. For breast cancer, a molecular classification consisting of five subtypes based on gene expression microarray data has been proposed. These subtypes have been reported to exist across several breast cancer microarray studies, and they have demonstrated some association with clinical outcome. A classification rule based on the method of centroids has been proposed for identifying the subtypes in new collections of breast cancer samples; the method is based on the similarity of the new profiles to the mean expression profile of the previously identified subtypes. Methods Previously identified centroids of five breast cancer subtypes were used to assign 99 breast cancer samples, including a subset of 65 estrogen receptor-positive (ER+) samples, to five breast cancer subtypes based on microarray data for the samples. The effect of mean centering the genes (i. e., transforming the expression of each gene so that its mean expression is equal to 0) on subtype assignment by method of centroids was assessed. Further studies of the effect of mean centering and of class prevalence in the test set on the accuracy of method of centroids classifications of ER status were carried out using training and test sets for which ER status had been independently determined by ligand-binding assay and for which the proportion of ER+ and ER-samples were systematically varied. Results When all 99 samples were considered, mean centering before application of the method of centroids appeared to be helpful for correctly assigning samples to subtypes, as evidenced by the expression of genes that had previously been used as markers to identify the subtypes. However, when only the 65 ER+ samples were considered for classification, many samples appeared to be misclassified, as evidenced by an unexpected distribution of ER+ samples among the resultant subtypes. When genes were mean centered before classification of samples for ER status, the accuracy of the ER subgroup assignments was highly dependent on the proportion of ER+ samples in the test set; this effect of subtype prevalence was not seen when gene expression data were not mean centered. Conclusions Simple corrections such as mean centering of genes aimed at microarray platform or batch effect correction can have undesirable consequences because patient population effects can easily be confused with these assay-related effects. Careful thought should be given to the comparability of the patient populations before attempting to force data comparability for purposes of assigning subtypes to independent subjects. C1 IFOM Fdn Inst, FIRC Oncol Mol, Mol Genet Canc Grp, I-20139 Milan, Italy. IRCCS, Inst Nazl Tumori, Dept Expt Oncol, Milan, Italy. IRCCS, Inst Nazl Tumori, Unit Med Stat & Biometry, Milan, Italy. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Univ Milan, Inst Med Stat & Biometry, Milan, Italy. RP Lusa, L (reprint author), IFOM Fdn Inst, FIRC Oncol Mol, Mol Genet Canc Grp, Via Adamello 16, I-20139 Milan, Italy. EM lusa@ifom-ieo-campus.it RI Reid, James/G-2496-2010; Lusa, Lara/C-6692-2015; De Cecco, Loris/K-7036-2016; gariboldi, manuela/K-4744-2016; OI Lusa, Lara/0000-0002-8981-2421; De Cecco, Loris/0000-0002-7066-473X; gariboldi, manuela/0000-0001-8406-165X; Reid, James/0000-0001-6997-2850; Ambrogi, Federico/0000-0001-9358-011X; Pierotti, Marco Alessandro/0000-0002-7431-8332; Biganzoli, Elia/0000-0003-1202-5873 NR 45 TC 62 Z9 62 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 21 PY 2007 VL 99 IS 22 BP 1715 EP 1723 DI 10.1093/jnci/djm216 PG 9 WC Oncology SC Oncology GA 233EA UT WOS:000251072000013 PM 18000217 ER PT J AU Tschritter, O Hennige, AM Preissl, H Porubska, K Schafer, SA Lutzenberger, W Machicao, F Birbaumer, N Fritsche, A Haring, HU AF Tschritter, Otto Hennige, Anita M. Preissl, Hubert Porubska, Katarina Schaefer, Silke A. Lutzenberger, Werner Machicao, Fausto Birbaumer, Niels Fritsche, Andreas Haering, Hans-Ulrich TI Cerebrocortical Beta Activity in Overweight Humans Responds to Insulin Detemir SO PLOS ONE LA English DT Article AB Background. Insulin stimulates cerebrocortical beta and theta activity in lean humans. This effect is reduced in obese individuals indicating cerebrocortical insulin resistance. In the present study we tested whether insulin detemir is a suitable tool to restore the cerebral insulin response in overweight humans. This approach is based on studies in mice where we could recently demonstrate increased brain tissue concentrations of insulin and increased insulin signaling in the hypothalamus and cerebral cortex following peripheral injection of insulin detemir. Methodology/Principal Findings. We studied activity of the cerebral cortex using magnetoencephalography in 12 lean and 34 overweight non-diabetic humans during a 2-step hyperinsulinemic euglycemic clamp (each step 90 min) with human insulin (HI) and saline infusion (S). In 10 overweight subjects we additionally performed the euglycemic clamp with insulin detemir (D). While human insulin administration did not change cerebrocortical activity relative to saline (p = 0.90) in overweight subjects, beta activity increased during D administration (basal 59 +/- 3 fT, 1(st) step 62 +/- 3 fT, 2(nd) step 66 +/- 5, p = 0.001, D vs. HI). As under this condition glucose infusion rates were lower with D than with HI (p = 0.003), it can be excluded that the cerebral effect is the consequence of a systemic effect. The total effect of insulin detemir on beta activity was not different from the human insulin effect in lean subjects (p = 0.78). Conclusions/Significance. Despite cerebrocortical resistance to human insulin, insulin detemir increased beta activity in overweight human subjects similarly as human insulin in lean subjects. These data suggest that the decreased cerebral beta activity response in overweight subjects can be restored by insulin detemir. C1 [Tschritter, Otto; Hennige, Anita M.; Schaefer, Silke A.; Machicao, Fausto; Fritsche, Andreas; Haering, Hans-Ulrich] Univ Tubingen, Dept Internal Med 4, Tubingen, Germany. [Preissl, Hubert; Porubska, Katarina; Lutzenberger, Werner; Birbaumer, Niels] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany. [Preissl, Hubert] Univ Arkansas Med Sci, Coll Med, Dept Obstet & Gynecol, Little Rock, AR 72205 USA. [Porubska, Katarina] Univ Eye Hosp, Dept Neuroophthalmol, Tubingen, Germany. [Birbaumer, Niels] NINDS, NIH, Bethesda, MD 20892 USA. RP Haring, HU (reprint author), Univ Tubingen, Dept Internal Med 4, Tubingen, Germany. EM hans-ulrich.haering@med.uni-tuebingen.de RI PreiSSl, Hubert/E-9070-2012 OI PreiSSl, Hubert/0000-0002-8859-4661 FU Deutsche Forschungsgemeinschaft ( DFG) [KFO114]; NovoNordisk, Copenhagen, Denmark FX This is an investigator initiated study. The study has been supported by a grant of the Deutsche Forschungsgemeinschaft ( DFG) as a part of the project "Klinische Forschergruppe 114'' ( KFO114) and by a research grant of NovoNordisk, Copenhagen, Denmark. NovoNordisk provided information about pharmacokinetics of insulin detemir for intravenous application. The funders had no further role in study design, collection and analysis of data, decision to publish, or preparation of the manuscript. NR 30 TC 27 Z9 33 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 21 PY 2007 VL 2 IS 11 AR e1196 DI 10.1371/journal.pone.0001196 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JB UT WOS:000207459200010 PM 18030331 ER PT J AU Aravind, L AF Aravind, L. TI Opening Pandora's Box: making biological discoveries through computational data exploration SO BIOLOGY DIRECT LA English DT Editorial Material ID DNA-BINDING PROTEINS; SEQUENCE; DOMAIN; HOMOLOGY; PAS C1 Natl Inst Hlth, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Inst Hlth, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov NR 14 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD NOV 20 PY 2007 VL 2 AR 29 DI 10.1186/1745-6150-2 PG 2 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 236NI UT WOS:000251309300001 PM 18028542 ER PT J AU Ranjit, N Diez-Roux, AV Shea, S Cushman, M Ni, H Seeman, T AF Ranjit, Nalini Diez-Roux, Ana V. Shea, Steven Cushman, Mary Ni, Hanyu Seeman, Teresa TI Socioeconomic position, race/ethnicity, and inflammation in the multi-ethnic study of atherosclerosis SO CIRCULATION LA English DT Article DE inflammation; race; ethnicity; risk factors; socioeconomic factors ID C-REACTIVE PROTEIN; DISEASE RISK-FACTORS; CARDIOVASCULAR-DISEASE; MARKERS; ASSOCIATION; STRESS; POPULATION; MECHANISMS; RESISTANCE; CYTOKINES AB Background - Low socioeconomic position is known to be associated with cardiovascular events and atherosclerosis. Reasons for these associations remain a topic of research. Inflammation could be an important mediating mechanism linking socioeconomic position to cardiovascular risk. Methods and Results - This cross-sectional study used data from the baseline examination of the Multi-Ethnic Study of Atherosclerosis (MESA), a study of 6814 men and women 45 to 84 years of age. Race- and ethnicity-stratified regression analyses were used to estimate associations of household income and education with C-reactive protein and interleukin-6 before and after adjustment for infection and medication use, psychosocial factors, behaviors, adiposity, and diabetes mellitus. Low income was associated with higher concentrations of interleukin-6 in all race/ethnic groups. Percent differences associated with 1-SD-lower income were 9% (95% confidence interval [CI], 7 to 11), 6% (95% CI, 1 to 10), 8% (95% CI, 4 to 11), and 8% (95% CI, 3 to 13) for whites, Chinese, blacks, and Hispanics. Low levels of education were associated with higher levels of interleukin-6 only among whites and blacks (percent difference in interleukin-6 associated with 1-SD-lower education: 9% [95% CI, 6 to 12] among Whites, and 7% [95% CI, 3 to 10] among blacks). Similar patterns were observed for C-reactive protein. Adiposity was the single most important factor explaining socioeconomic position associations, especially among blacks and whites. A smaller effect was seen for psychosocial factors and behaviors in all race groups. Conclusions - Both household income and education are associated with inflammation, but associations vary across race/ethnic groups. Associations likely result from socioeconomic position patterning of adiposity and other factors. C1 Univ Michigan, Ctr Social Epidemiol & Populat Hlth, Ann Arbor, MI 48104 USA. Columbia Univ, Dept Med, New York, NY USA. Columbia Univ, Dept Epidemiol, New York, NY USA. Univ Vermont, Dept Med, Birmingham, W Midlands, England. NIH, NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA USA. RP Ranjit, N (reprint author), Univ Michigan, Ctr Social Epidemiol & Populat Hlth, 1214 S Univ, Ann Arbor, MI 48104 USA. EM nranjit@umich.edu FU NHLBI NIH HHS [R01 HL076831, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95169]; NICHD NIH HHS [R24 HD047861] NR 30 TC 71 Z9 72 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 20 PY 2007 VL 116 IS 21 BP 2383 EP 2390 DI 10.1161/CIRCULATIONAHA.107.706226 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 233GU UT WOS:000251079300005 PM 18025402 ER PT J AU Nabel, EG AF Nabel, Elizabeth G. TI Notes from the director of the national heart, lung, and blood institute: Shaping the future of research: The NHLBI strategic plan SO CIRCULATION LA English DT Article DE cardiovascular diseases; health and welfare planning; research priorities C1 NIH, NHLBI, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NIH, NHLBI, Bldg 31-5A48,31 Ctr Dr, Bethesda, MD 20892 USA. EM nabele@nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 20 PY 2007 VL 116 IS 21 BP 2479 EP 2480 DI 10.1161/CIRCULATIONAHA.107.740951 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 233GU UT WOS:000251079300015 PM 18025405 ER PT J AU Harris, L Fritsche, H Mennel, R Norton, L Ravdin, P Taube, S Somerfield, MR Hayes, DF Bast, RC AF Harris, Lyndsay Fritsche, Herbert Mennel, Robert Norton, Larry Ravdin, Peter Taube, Sheila Somerfield, Mark R. Hayes, Daniel F. Bast, Robert C., Jr. TI American society of clinical oncology 2007 update of recommendations for the use of tumor markers in breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CARCINOMA-IN-SITU; POLYMERASE-CHAIN-REACTION; BONE-MARROW MICROMETASTASES; UROKINASE-PLASMINOGEN-ACTIVATOR; NIPPLE ASPIRATE FLUID; SURGICAL ADJUVANT BREAST; ESTROGEN-RECEPTOR STATUS; CYTOKERATIN-19 MESSENGER-RNA; GENE-EXPRESSION PATTERNS; TOPOISOMERASE-II-ALPHA AB Purpose To update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast cancer. Methods For the 2007 update, an Update Committee composed of members from the full Panel was formed to complete the review and analysis of data published since 1999. Computerized literature searches of MEDLINE and the Cochrane Collaboration Library were performed. The Update Committee's literature review focused attention on available systematic reviews and meta-analyses of published tumor marker studies. In general, significant health outcomes (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used for making recommendations. Recommendations and Conclusions Thirteen categories of breast tumor markers were considered, six of which were new for the guideline. The following categories showed evidence of clinical utility and were recommended for use in practice: CA 15-3, CA 27.29, carcinoembryonic antigen, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, urokinase plasminogen activator, plasminogen activator inhibitor 1, and certain multiparameter gene expression assays. Not all applications for these markers were supported, however. The following categories demonstrated insufficient evidence to support routine use in clinical practice: DNA/ploidy by flow cytometry, p53, cathepsin D, cyclin E, proteomics, certain multiparameter assays, detection of bone marrow micrometastases, and circulating tumor cells. C1 Soc Clin Oncol, Alexandria, VA 22314 USA. Yale Univ, Yale Canc Ctr, New Haven, CT USA. MD Anderson Canc Ctr, Houston, TX USA. Texas Oncol PA, Dallas, TX USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Bethesda, MD 20892 USA. Amer Soc Clin Oncol, Alexandria, VA USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. RP Harris, L (reprint author), Soc Clin Oncol, 1900 Duke St,Suite 200, Alexandria, VA 22314 USA. RI Bast, Robert/E-6585-2011; OI Bast, Robert/0000-0003-4621-8462; Norton, Larry/0000-0003-3701-9250 NR 323 TC 1226 Z9 1283 U1 24 U2 202 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2007 VL 25 IS 33 BP 5287 EP 5312 DI 10.1200/JCO.2007.14.2364 PG 26 WC Oncology SC Oncology GA 233EY UT WOS:000251074400024 PM 17954709 ER PT J AU Vaccarino, V Johnson, BD Sheps, DS Reis, SE Kelsey, SF Bittner, V Rutledge, T Shaw, LJ Sopko, G Metz, CNB AF Vaccarino, Viola Johnson, B. Delia Sheps, David S. Reis, Steven E. Kelsey, Sheryl F. Bittner, Vera Rutledge, Thomas Shaw, Leslee J. Sopko, George Metz, C. Noel Bairey TI Depression, inflammation and incident cardiovascular disease in women with suspected coronary ischemia - The national heart, lung, and blood institute-sponsored WISE study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; ACUTE-PHASE PROTEINS; MYOCARDIAL-INFARCTION; MAJOR DEPRESSION; ARTERY-DISEASE; RISK-FACTOR; MORTALITY; MARKERS; SYMPTOMS; PREDICTION AB Objectives The purpose of this study was to examine prospectively whether inflammation explains the relationship between depression and cardiovascular disease (CVD). Background It is unclear whether inflammation is a mechanism linking depression to CVD. Methods We measured C-reactive protein (CRP) and interleukin (IL)-6 in 559 women with suspected coronary ischemia who completed the Beck Depression Inventory (BDI) at baseline and were followed over 5.9 years. We considered indicators of past and current depression to classify women into 3 groups: 1) depression, having both elevated depressive symptoms (BDI >= 10) and a previous diagnosis of depression requiring treatment; 2) possible depression, having either indicator but not both; and 3) no depression, having neither indicator of depression. The main outcome was incidence of CVD events (hospital stays for nonfatal myocardial infarction, stroke, congestive heart failure, and CVD-related mortality). Results Compared with women without depression, women with depression had a 70% higher CRP (p = 0.0008) and a 25% higher IL-6 (p = 0.04), whereas women with possible depression had 30% higher CRP (p = 0.02) and 28% higher IL-6 (p = 0.01). Depression was a significant predictor of CVD (hazard ratio 2.58, p = 0.0009), but possible depression was not (hazard ratio 1.12, p = 0.68). Adjustment for other patient factors did not substantially affect the results. Addition of CRP decreased the estimate for depression by 13% and addition of IL-6 decreased it by 4%. Both depression and inflammatory biomarkers remained independent predictors of outcome. Conclusions Despite their robust association with depression, inflammatory biomarkers explain only a small portion of the association between depression and CVD incidence. C1 Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA 30322 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Cardiovasc Inst, Dept Med, Pittsburgh, PA 15261 USA. Univ Florida, Div Cardiovasc Med, Dept Med, Gainesville, FL USA. Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Div Cardiol, Dept Med, Los Angeles, CA 90048 USA. NIH, NHLBI, Bethesda, MD 20892 USA. RP Vaccarino, V (reprint author), Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA 30322 USA. EM viola.vaccarino@emory.edu RI Reis, Steven/J-3957-2014; OI Bittner, Vera/0000-0001-9456-850X FU NCRR NIH HHS [M01-RR00425]; NHLBI NIH HHS [N01-HV-68164, K24HL077506, N01-HV-68161, N01-HV-68162, N01-HV-68163] NR 45 TC 132 Z9 138 U1 1 U2 8 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 NOV 20 PY 2007 VL 50 IS 21 BP 2044 EP 2050 DI 10.1016/j.jacc.2007.07.069 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 234PY UT WOS:000251177200005 PM 18021871 ER PT J AU Holmes, EC AF Holmes, Edward C. TI When HIV spread afar SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; ORIGIN C1 Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. EM echl5@psu.edu OI Holmes, Edward/0000-0001-9596-3552 NR 10 TC 5 Z9 6 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2007 VL 104 IS 47 BP 18351 EP 18352 DI 10.1073/pnas.0709179104 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 236HB UT WOS:000251292500003 PM 18003901 ER PT J AU Hong, SH Cho, YW Yu, LR Yu, H Veenstra, TD Ge, K AF Hong, SunHwa Cho, Young-Wook Yu, Li-Rong Yu, Hong Veenstra, Timothy D. Ge, Kai TI Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE histone methylation; transcriptional regulation ID EMBRYONIC STEM-CELLS; DEVELOPMENTAL REGULATORS; CONTAINING PROTEINS; ACTIVE GENES; METHYLATION; POLYCOMB; LSD1; FAMILY; TRANSCRIPTION; COMPLEX AB Covalent modifications of histones, such as acetylation and methylation, play important roles in the regulation of gene expression. Histone lysine methylation has been implicated in both gene activation and repression, depending on the specific lysine (K) residue that becomes methylated and the state of methylation (mono-, di-, or trimethylation). Methylation on K4, K9, and K36 of histone H3 has been shown to be reversible and can be removed by site-specific clemethylases. However, the enzymes that antagonize methylation on K27 of histone H3 (H3K27), an epigenetic mark important for embryonic stem cell maintenance, Polycombmediated gene silencing, and X chromosome inactivation have been elusive. Here we show the JmjC domain-containing protein UTX (ubiquitously transcribed tetratricopepticle repeat, X chromosome), as well as the related JMJID3 aumonji domain containing 3), specifically removes methyl marks on H3K27 in vitro. Further, the clemethylase activity of UTX requires a catalytically active JmjC domain. Finally, overexpression of UTX and JMJD3 leads to reduced di- and trimethylation on H3K27 in cells, suggesting that UTX and JMJD3 may function as H3K27 clemethylases in vivo. The identification of UTX and JMJID3 as H3K27-specific clemethylases provides direct evidence to indicate that similar to methylation on K4, K9, and K36 of histone H3, methylation on H311 < 27 is also reversible and can be dynamically regulated by site-specif ic histone methyltransferases and clemethylases. C1 NIDDK, NIH, Clin Epidemiol Branch, Nucl Receptor Biol Sect, Bethesda, MD 20892 USA. Natl Canc Inst, SAIC Frederick, Lab Prote & Analyst Technol, Adv Technol Program, Ft Detrick, MD 21702 USA. RP Ge, K (reprint author), NIDDK, NIH, Clin Epidemiol Branch, Nucl Receptor Biol Sect, Bethesda, MD 20892 USA. EM kaig@niddk.nih.gov RI Cho, Young-Wook /F-8269-2011; OI Ge, Kai/0000-0002-7442-5138 FU Intramural NIH HHS [Z99 DK999999, Z01 DK047055-01, Z01 DK075003-04]; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIDDK NIH HHS [ZIADK047055-03, ZIADK075003-06, ZIADK075017-01] NR 26 TC 244 Z9 256 U1 1 U2 13 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 NOV 20 PY 2007 VL 104 IS 47 BP 18439 EP 18444 DI 10.1073/pnas.0707292104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 236HB UT WOS:000251292500019 PM 18003914 ER PT J AU Noda, Y Berlett, BS Stadtman, ER Aponte, A Morgan, M Shen, RF AF Noda, Yasuko Berlett, Barbara S. Stadtman, Earl R. Aponte, Angel Morgan, Meghan Shen, Rong-Fong TI Identification of enzymes and regulatory proteins in Escherichia coli that are oxidized under nitrogen, carbon, or phosphate starvation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OXIDATIVELY DENATURED PROTEINS; GLUTAMINE-SYNTHETASE; BACTERIAL SENESCENCE; DEGRADATION; CELLS; INACTIVATION; TURNOVER AB Using proteomic technologies, we identified 62 proteins that are oxidized to carbonyl derivatives during growth of Escherichia coli under nitrogen starvation (NS), carbon starvation (CS), and phosphate starvation (PS) conditions. The carbonylated proteins were converted to 2,4-dinitrophenylhydrazone derivatives and these were identified using Western blotting and mass spectrometry by searching E. coli proteins in the Swiss-Prot and/or NCBI databases. Fourteen of the oxidized proteins were formed under both NS and CS conditions, and only three proteins were specifically oxidized under PS conditions. Interestingly, the carbonyl content of proteins in crude extracts of cells harvested after 48 h of stationary growth under NS and CS was significantly lower than that observed at mid-log and end-log phases of growth. In contrast, the carbonyl content of proteins in extracts of cells grown under PS conditions was fairly constant during comparable periods of growth. C1 NHLBI, NIH, Biochem Lab, Biochem & Biophys Ctr, Bethesda, MD 20892 USA. NHLBI, NIH, Prote Core Facil, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, NIH, Biochem Lab, Biochem & Biophys Ctr, Bldg 10, Bethesda, MD 20892 USA. EM erstadtman@nih.gov OI Morgan-Smith, Meghan/0000-0001-5122-2330 FU Intramural NIH HHS NR 23 TC 13 Z9 13 U1 0 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 NOV 20 PY 2007 VL 104 IS 47 BP 18456 EP 18460 DI 10.1073/pnas.0709368104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 236HB UT WOS:000251292500022 PM 18003895 ER PT J AU Caceres, M Sullivan, RT Thomas, JW AF Caceres, Mario Sullivan, Robert T. Thomas, James W. CA Natl Institutes Hlth Intramural S TI A recurrent inversion on the eutherian X chromosome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE duplication; gene conversion; inversion polymorphism ID PRIMATE SEGMENTAL DUPLICATIONS; SEVERE HEMOPHILIA-A; GENE CONVERSION; HUMAN GENOME; SEQUENCE ALIGNMENT; STRUCTURAL VARIATION; MAMMALIAN EVOLUTION; INVERTED REPEATS; REARRANGEMENTS; REGIONS AB Chromosomal inversions have an important role in evolution, and an increasing number of inversion polymorphisms are being identified in the human population. The evolutionary history of these inversions and the mechanisms by which they arise are therefore of significant interest. Previously, a polymorphic inversion on human chromosome Xq28 that includes the FLNA and EMD loci was discovered and hypothesized to have been the result of nonallelic homologous recombination (NAHR) between near-identical inverted duplications flanking this region. Here, we carried out an in-depth study of the orthologous region in 27 additional eutherians and report that this inversion is not specific to humans, but has occurred independently and repeatedly at least 10 times in multiple eutherian lineages. Moreover, inverted duplications flank the FLNA-EMD region in all 16 species for which high-quality sequence assemblies are available. Based on detailed sequence analyses, we propose a model in which the observed inverted duplications originated from a common duplication event that predates the eutherian radiation. Subsequent gene conversion homogenized the duplications, thereby providing a continuous substrate for NAHR that led to the recurrent inversion of this segment of the genome. These results provide an extreme example in support of the evolutionary breakpoint reusage hypothesis and point out that some near-identical human segmental duplications may, in fact, have originated > 100 million years ago. C1 Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. Ctr Genom Regulat, Genes & Dis Program, Barcelona 08003, Spain. NHGRI, NIH, Genome Technol Branch, Bethesda, MD 20892 USA. Natl Inst Hlth Intramural Sequencing Ctr, NHGRI, NIH, Bethesda, MD 20892 USA. RP Thomas, JW (reprint author), Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. EM jthomas@genetics.emory.edu RI Caceres, Mario/A-6379-2009 OI Caceres, Mario/0000-0002-7736-3251 FU Intramural NIH HHS NR 56 TC 24 Z9 24 U1 2 U2 4 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 NOV 20 PY 2007 VL 104 IS 47 BP 18571 EP 18576 DI 10.1073/pnas.0706604104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 236HB UT WOS:000251292500042 PM 18003915 ER PT J AU Wang, T Zeng, J Lowe, CB Sellers, RG Salama, SR Yang, M Burgess, SM Brachmann, RK Haussler, D AF Wang, Ting Zeng, Jue Lowe, Craig B. Sellers, Robert G. Salama, Sofie R. Yang, Min Burgess, Shawn M. Brachmann, Rainer K. Haussler, David TI Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FACTOR-BINDING-SITES; HUMAN GENOME; TRANSPOSABLE ELEMENTS; NONCODING SEQUENCES; GENE; EVOLUTION; EXPRESSION; DATABASE; UPDATE; TOOL AB The evolutionary forces that establish and hone target gene networks of transcription factors are largely unknown. Transposition of retroelements may play a role, but its global importance, beyond a few well described examples for isolated genes, is not clear. We report that LTR class I endogenous retrovirus (ERV) retroelements impact considerably the transcriptional network of human tumor suppressor protein p53. A total of 1,509 of approximate to 319,000 human ERV LTR regions have a near-perfect p53 DNA binding site. The LTR10 and MER61 families are particularly enriched for copies with a p53 site. These ERV families are primate-specific and transposed actively near the time when the New World and Old World monkey lineages split. Other mammalian species lack these p53 response elements. Analysis of published genomewide ChIP data for p53 indicates that more than one-third of identified p53 binding sites are accounted for by ERV copies with a p53 site. ChIP and expression studies for individual genes indicate that human ERV p53 sites are likely part of the p53 transcriptional program and direct regulation of p53 target genes. These results demonstrate how retroelements can significantly shape the regulatory network of a transcription factor in a species-specific manner. C1 Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. NIH, NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. RP Brachmann, RK (reprint author), Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92697 USA. EM rbrachma@uci.edu; haussler@soe.ucsc.edu OI Burgess, Shawn/0000-0003-1147-0596 NR 44 TC 155 Z9 160 U1 1 U2 17 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 NOV 20 PY 2007 VL 104 IS 47 BP 18613 EP 18618 DI 10.1073/pnas.0703637104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 236HB UT WOS:000251292500049 PM 18003932 ER PT J AU Boyer, JD Robinson, TM Kutzler, MA Vansant, G Hokey, DA Kumar, S Parkinson, R Wu, L Sidhu, MK Pavlakis, GN Felber, BK Brown, C Silvera, P Lewis, MG Monforte, J Waldmann, TA Eldridge, J Weiner, DB AF Boyer, Jean D. Robinson, Tara M. Kutzler, Michele A. Vansant, Gordon Hokey, David A. Kumar, Sanjeev Parkinson, Rose Wu, Ling Sidhu, Maninder K. Pavlakis, George N. Felber, Barbara K. Brown, Charles Silvera, Peter Lewis, Mark G. Monforte, Joseph Waldmann, Thomas A. Eldridge, John Weiner, David B. TI Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV vaccine; immune response; cytokine adjuvant; T cell immunity ID CD8(+) T-CELLS; CELLULAR IMMUNE-RESPONSES; RHESUS MACAQUES; DNA VACCINE; IN-VIVO; SHIV89.6P CHALLENGE; SIV ANTIGENS; HIV-1; INFECTION; VECTORS AB The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-gamma-producing CD8(+) and CD4(+) effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-gamma was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication. C1 NCI, Metab Branch, Frederick, MD 21702 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Althea Technol Inc, Genomix, San Diego, CA 92121 USA. Wyeth, Vaccine Discovery, Pearl River, NY 10965 USA. NCI, Vaccine Branch, Frederick, MD 21702 USA. NIAID, Viral Pathogenesis & Vaccine Branch, Mol Microbiol Lab, Bethesda, MD 20892 USA. So Res Inst, Div Life Sci, Frederick, MD 21701 USA. Bioqual, Res Sect, Rockville, MD 20850 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Bldg 10,Room 4N115, Frederick, MD 21702 USA. EM tawald@helix.nih.gov; dbweiner@mail.med.upenn.edu RI Weiner, David/H-8579-2014 FU Intramural NIH HHS; NIAID NIH HHS [N01-AI-50010, N01AI50010]; PHS HHS [P01-A1-071739, R01-A1-071186] NR 66 TC 65 Z9 67 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 NOV 20 PY 2007 VL 104 IS 47 BP 18648 EP 18653 DI 10.1073/pnas.0709198104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 236HB UT WOS:000251292500055 PM 18000037 ER PT J AU De Silva, FS Lewis, W Berglund, P Koonin, EV Moss, B AF De Silva, Frank S. Lewis, Whitney Berglund, Peter Koonin, Eugene V. Moss, Bernard TI Poxvirus DNA primase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA replication; nucleocytoplasmic large DNA viruses; RNA primer; vaccinia virus ID VACCINIA VIRUS-DNA; MOUSE L-CELLS; VIRAL-DNA; RNA-POLYMERASE; INFECTED CELLS; D5 PROTEIN; REPLICATION; GENE; GLYCOSYLASE; SEQUENCE AB Poxviruses are large enveloped viruses that replicate in the cytoplasm of vertebrate or invertebrate cells. At least six virus-encoded proteins are required for synthesis and processing of the double-stranded DNA genome of vaccinia virus, the prototype member of the family. One of these proteins, IDS, is an NTPase that contains an N-terminal archaeoeukaryotic primase domain and a C-terminal superfamily III helicase domain. Here we report that individual conserved aspartic acid residues in the predicted primase active site were required for in vivo complementation of infectious virus formation as well as genome and plasmid replication. Furthermore, purified recombinant D5 protein synthesized oligoribonucleotides in vitro. Incorporation of label from [alpha-P-32]CTP or [alpha-P-32]UTP into a RNase-sensitive and DNase-resistant product was demonstrated by using single-stranded circular bacteriophage DNA templates and depended on ATP or GTP and a divalent cation. Mutagenesis studies showed that the primase and NTPase activities of the recombinant D5 protein could be independently inactivated. Highly conserved orthologs of D5 are present in all poxviruses that have been sequenced, and more diverged orthologs are found in members of all other families of nucleocytoplasmic large DNA viruses. These viral primases may have roles in initiation of DNA replication or lagging-strand synthesis and represent potential therapeutic targets. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. AlphaVax, Res Triangle Pk, NC 27709 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS NR 52 TC 40 Z9 41 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2007 VL 104 IS 47 BP 18724 EP 18729 DI 10.1073/pnas.0709276104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 236HB UT WOS:000251292500068 PM 18000036 ER PT J AU Shnyrova, AV Ayllon, J Mikhalyov, II Villar, E Zimmerberg, J Frolov, VA AF Shnyrova, Anna V. Ayllon, Juan Mikhalyov, Ilya I. Villar, Enrique Zimmerberg, Joshua Frolov, Vadim A. TI Vesicle formation by self-assembly of membrane-bound matrix proteins into a fluidlike budding domain SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NEWCASTLE-DISEASE VIRUS; COAT PROTEINS; FISSION PORE; LIPOSOMES; RELEASE; MECHANISMS; CURVATURE; PARTICLES; DYNAMICS; FUSION AB The shape of enveloped viruses depends critically on an internal protein matrix, yet it remains unclear how the matrix proteins control the geometry of the envelope membrane. We found that matrix proteins purified from Newcastle disease virus adsorb on a phospholipid bilayer and condense into fluidlike domains that cause membrane deformation and budding of spherical vesicles, as seen by fluorescent and electron microscopy. Measurements of the electrical admittance of the membrane resolved the gradual growth and rapid closure of a bud followed by its separation to form a free vesicle. The vesicle size distribution, confined by intrinsic curvature of budding domains, but broadened by their merger, matched the virus size distribution. Thus, matrix proteins implement domain-driven mechanism of budding, which suffices to control the shape of these proteolipid vesicles. C1 NICHHD, NIH, Lab Cell & Mol Biophys, Bethesda, MD 20892 USA. Univ Salamanca, Dept Bioquim & Biol Mol, E-37007 Salamanca, Spain. Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia. RP Zimmerberg, J (reprint author), NICHHD, NIH, Lab Cell & Mol Biophys, Bethesda, MD 20892 USA. EM joshz@mail.nih.gov OI Frolov, Vadim/0000-0002-0653-5669 FU Intramural NIH HHS NR 38 TC 34 Z9 34 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 19 PY 2007 VL 179 IS 4 BP 627 EP 633 DI 10.1083/jcb.200705062 PG 7 WC Cell Biology SC Cell Biology GA 233GD UT WOS:000251077500009 PM 18025300 ER PT J AU Ilani, T Khanna, C Zhou, M Veenstra, TD Bretscher, A AF Ilani, Tal Khanna, Chand Zhou, Ming Veenstra, Timothy D. Bretscher, Anthony TI Immune synapse formation requires ZAP-70 recruitment by ezrin and CD43 removal by moesin SO JOURNAL OF CELL BIOLOGY LA English DT Article ID EZRIN/RADIXIN/MOESIN ERM PROTEINS; ACTIN-BINDING-SITE; IMMUNOLOGICAL SYNAPSE; ENDOTHELIAL-CELLS; TYROSINE KINASE; T-LYMPHOCYTES; RADIXIN; ACTIVATION; CYTOSKELETON; FAMILY AB Immunological synapse (IS) formation involves receptor ligand pair clustering and intracellular signaling molecule recruitment with a coincident removal of other membrane proteins away from the IS. As micro. lament membrane linkage is critical to this process, we investigated the involvement of ezrin and moesin, the two ezrin/radixin/moesin proteins expressed in T cells. We demonstrate that ezrin and moesin, which are generally believed to be functionally redundant, are differentially localized and have important and complementary functions in IS formation. Specifically, we find that ezrin directly interacts with and recruits the signaling kinase ZAP-70 to the IS. Furthermore, the activation of ezrin by phosphorylation is essential for this process. In contrast, moesin dephosphorylation and removal, along with CD43, are necessary to prepare a region of the cell cortex for IS. Thus, ezrin and moesin have distinct and critical functions in the T cell cortex during IS formation. C1 Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. Ctr Canc Res, NCI, Comparat Oncol Program, Rockville, MD 20850 USA. SAIC Frederick Inc, NCI, Lab Prot & Analyt Technol, Ft Detrick, MD 21702 USA. RP Bretscher, A (reprint author), Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. EM apb5@cornell.edu FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 52 TC 67 Z9 67 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 19 PY 2007 VL 179 IS 4 BP 733 EP 746 DI 10.1083/jcb.200707199 PG 14 WC Cell Biology SC Cell Biology GA 233GD UT WOS:000251077500017 PM 18025306 ER PT J AU Zhou, QF Hidajat, R Peng, B Venzon, D Aldrich, MK Richardson, E Lee, EM Kalyanaraman, V Grimes, G Gomez-Roman, VR Summers, LE Malkevich, N Robert-Guroff, M AF Zhou, Qifeng Hidajat, Rachmat Peng, Bo Venzon, David Aldrich, M. Kristine Richardson, Ersell Lee, Eun Mi Kalyanaraman, V. S. Grimes, George Gomez-Roman, V. Raul Summers, L. Ebonita Malkevich, Nina Robert-Guroff, Marjorie TI Comparative evaluation of oral and intranasal priming with replication-competent adenovirus 5 host range mutant (Ad5hr)-simian immunodeficiency virus (SIV) recombinant vaccines on immunogenicity and protective efficacy against SIVmac251 SO VACCINE LA English DT Article DE AIDS; adenovirus recombinant vaccines; mucosal immunity ID SIMIAN-IMMUNODEFICIENCY-VIRUS; T-CELL DEPLETION; RHESUS MACAQUES; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSES; HIV-1 INFECTION; IMMUNOLOGICAL RESPONSES; GASTROINTESTINAL-TRACT; MONOCLONAL-ANTIBODIES; VAGINAL TRANSMISSION AB Oral, replication-competent Ad-HIV vaccines are advancing to human trials. Previous evaluation of protective efficacy in non-human primates has primarily followed upper respiratory tract administrations. Here we compared sequential oral (O/O) versus intranasal/oral (I/O) priming of rhesus macaques with Ad5 host range mutant-SIV recombinants expressing SIV env/rev, gag, and nef genes followed by boosting with SIV gp 120 protein. Cellular immune responses in PBMC were stronger and more frequent after I/O administration. Both groups developed mucosal immunity, including memory cells in bronchial alveolar lavage, and gut-homing receptors on PBMC. Following intrarectal SIVmac251 challenge, both groups exhibited equivalent, significant protection and robust post-challenge cellular immunity. Our results illustrate the promise of oral replication-competent Ad-recombinant vaccines. Pre-challenge PBMC ELISPOT and proliferative responses did not predict protection in the O/O group, highlighting the need for simple, non-invasive methods to reliably assess mucosal immunity. (c) 2007 Elsevier Ltd. All rights reserved. C1 NCI, NIH, Vaccine Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Adv Biosci Labs Inc, Kensington, NSW 20895, Australia. NIH, Clin Ctr Pharm Dept, Bethesda, MD 20892 USA. RP Robert-Guroff, M (reprint author), NCI, NIH, Vaccine Branch, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov FU Intramural NIH HHS NR 57 TC 36 Z9 36 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 19 PY 2007 VL 25 IS 47 BP 8021 EP 8035 DI 10.1016/j.vaccine.2007.09.017 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 236VL UT WOS:000251331400006 PM 17935840 ER PT J AU Lo, PHY Xie, D Chan, KC Xu, FP Kuzmin, I Lerman, MI Law, S Chua, D Sham, J Lung, ML AF Lo, Paulisally Hau Yi Xie, Dan Chan, King Chi Xu, Fang-Ping Kuzmin, Igor Lerman, Michael I. Law, Simon Chua, Daniel Sham, Jonathan Lung, Maria Li TI Reduced expression of RASSF1A in esophageal and nasopharyngeal carcinomas significantly correlates with tumor stage SO CANCER LETTERS LA English DT Article DE RASSF1A; esophageal cancer; nasopharyngeal carcinoma; tissue microarray ID SUPPRESSOR GENE; CHROMOSOME 3P; EPIGENETIC INACTIVATION; 3P21.3; LUNG; ASSOCIATION; METHYLATION; PROGRESSION; SPECIMENS; DELETION AB Reduced expression or loss of tumor suppressor genes play a key role in many cancers. In this study, we investigated the role of RASSF1A in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). We detected the down-regulated expression of both RASSF1A transcripts and protein in tumor tissues using RT-PCR and tissue microarray immunohistochemical staining analyses. Down-regulated expression of RASSF1A showed a significant association with WHO grade, tumor status, and lymph node metastasis, showing its possible utility as a biomarker for clinical specimens. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Hong Kong Univ Sci & Technol, Canc Res Ctr, Dept Biol, Hong Kong, Peoples R China. Sun Yat Sen Univ, Ctr Canc, State Key Lab Onc So China, Guangzhou, Peoples R China. Sun Yat Sen Univ, Affiliated Hosp 1, Dept Pathol, Guangzhou, Peoples R China. Sci Applicat Int Corp Frederick Inc, Natl Canc Inst, Basic Res Program, Frederick, MD USA. Natl Canc Inst, Ctr Canc Res, Immunobiol Lab, Canc Causing Genes Sect, Frederick, MD USA. Univ Hong Kong, Dept Surg, Hong Kong, Peoples R China. Univ Hong Kong, Dept Clin Oncol, Hong Kong, Peoples R China. RP Lung, ML (reprint author), Hong Kong Univ Sci & Technol, Canc Res Ctr, Dept Biol, Hong Kong, Peoples R China. EM bomaria@ust.hk RI Chua, Daniel/C-4253-2009; Law, Simon/C-4324-2009 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 23 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 18 PY 2007 VL 257 IS 2 BP 199 EP 205 DI 10.1016/j.canlet.2007.07.018 PG 7 WC Oncology SC Oncology GA 230YK UT WOS:000250912100007 PM 17720308 ER PT J AU Voortman, J Checinska, A Giaccone, G AF Voortman, Jens Checinska, Agnieszka Giaccone, Giuseppe TI The proteasomal and apoptotic phenotype determine bortezomib sensitivity of non-small cell lung cancer cells SO MOLECULAR CANCER LA English DT Article ID INHIBITOR BORTEZOMIB; SPECIFICITY; RESISTANCE; SUBUNITS; THERAPY; PS-341 AB Bortezomib is a novel anti-cancer agent which has shown promising activity in non-small lung cancer (NSCLC) patients. However, only a subset of patients respond to this treatment. We show that NSCLC cell lines are differentially sensitive to bortezomib, IC(50) values ranging from 5 to 83 nM. The apoptosis-inducing potential of bortezomib in NSCLC cells was found to be dependent not only on the apoptotic phenotype but also on the proteasomal phenotype of individual cell lines. Upon effective proteasome inhibition, H460 cells were more susceptible to apoptosis induction by bortezomib than SW1573 cells, indicating a different apoptotic phenotype. However, exposure to a low dose of bortezomib did only result in SW1573 cells, and not in H460 cells, in inhibition of proteasome activity and subsequent apoptosis. This suggests a different proteasomal phenotype as well. Additionally, overexpression of anti- apoptotic protein Bcl-2 in H460 cells did not affect the proteasomal phenotype of H460 cells but did result in decreased bortezomib-induced apoptosis. In conclusion, successful proteasome-inhibitor based treatment strategies in NSCLC face the challenge of having to overcome apoptosis resistance as well as proteasomal resistance of individual lung cancer cells. Further studies in NSCLC are warranted to elucidate underlying mechanisms. C1 [Voortman, Jens; Checinska, Agnieszka; Giaccone, Giuseppe] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands. [Checinska, Agnieszka] Univ Michigan, Comprehens Canc Ctr 4217, Dept Dermatol, Ann Arbor, MI 48109 USA. [Giaccone, Giuseppe] NCI, Natl Inst Hlth, Med Oncol Branch, Bethesda, MD 20892 USA. RP Voortman, J (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands. EM j.voortman@vumc.nl; agnieszk@med.umich.edu; giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 27 TC 12 Z9 12 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD NOV 17 PY 2007 VL 6 AR 73 DI 10.1186/1476-4598-6-73 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 250CL UT WOS:000252277500001 PM 18021420 ER PT J AU Artz, AS Leng, SX Yeh, SS McKenna, PJ Thoni, SN Audhya, P Doucette, S Flores, IQ Geloo, ZS Ershler, WB AF Artz, Andrew S. Leng, Sean X. Yeh, Sbing-Shing McKenna, Patrick J. Thoni, Samisha N. Audhya, Paul Doucette, Steve Flores, Irene Q. Geloo, Z. Shana Ershler, William B. TI Baseline characteristics of 65 subjects in the correction of anemia with darbepoetin alfa (DA) in the community-dwelling frail elderly (CAFE) study SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Artz, Andrew S.] Univ Chicago, Chicago, IL 60637 USA. [Leng, Sean X.] Johns Hopkins Univ, Baltimore, MD USA. [Yeh, Sbing-Shing] SUNY Stony Brook, Stony Brook, NY 11794 USA. [McKenna, Patrick J.; Thoni, Samisha N.; Audhya, Paul] Amgen Inc, Thousand Oaks, CA 91320 USA. [Doucette, Steve] Univ Ottawa, Ottawa, ON, Canada. [Flores, Irene Q.; Geloo, Z. Shana; Ershler, William B.] IASIA, Washington, DC USA. [Ershler, William B.] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3779 BP 11B EP 12B PN 2 PG 2 WC Hematology SC Hematology GA 233OV UT WOS:000251101100035 ER PT J AU Calado, RT Regal, JA Yewdell, WT Falcao, RP Figueiredo, L Estey, EH Zago, MA Hills, M Chanock, ST Lansdorp, PM Young, NS AF Calado, Rodrigo T. Regal, Joshua A. Yewdell, William T. Falcao, Roberto P. Figueiredo, Leandro Estey, Elihu H. Zago, Marco A. Hills, Mark Chanock, Stephen T. Lansdorp, Peter M. Young, Neal S. TI Constitutional loss-of-function mutations in telomerase are genetic risk factors for acute myeloid leukemia SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Calado, Rodrigo T.; Regal, Joshua A.; Yewdell, William T.; Young, Neal S.] NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Falcao, Roberto P.; Figueiredo, Leandro; Zago, Marco A.] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Internal Med, Ribeirao Preto, SP, Brazil. [Estey, Elihu H.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX USA. [Hills, Mark; Lansdorp, Peter M.] Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. [Chanock, Stephen T.] NIH, NCI, Pediat Oncol Unit, Gaithersburg, MD USA. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 16 BP 13A EP 13A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800017 ER PT J AU Kim-Shapiro, DB He, XJ Azarov, I Richardson, J King, SB Gladwin, MT AF Kim-Shapiro, Daniel B. He, Xiaojun Azarov, Ivan Richardson, Jodi King, S. Bruce Gladwin, Mark T. TI Potential of Angeli's salt to reduce nitric oxide scavenging in hemolysis SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Kim-Shapiro, Daniel B.; He, Xiaojun; Azarov, Ivan; Richardson, Jodi; King, S. Bruce] Wake Forest Univ, Winston Salem, NC 27109 USA. [Gladwin, Mark T.] NIH, NHLBI, Vascular Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3788 BP 14B EP 14B PN 2 PG 1 WC Hematology SC Hematology GA 233OV UT WOS:000251101100044 ER PT J AU Aliyu, ZY Vandana, S Mamman, AI Babadoko, A Akpanpe, P Attah, E Suleiman, Y Aliyu, N Yusuf, J Mendelsohn, L Coles, W Danbauchi, S Taylor, J Castro, O Gordeuk, VR Blackwelder, WC Kato, GJ Gladwin, MT AF Aliyu, Zakari Y. Vandana, Sachdev Mamman, Aisha I. Babadoko, Aliyu Akpanpe, Peter Attah, Ester Suleiman, Yusuf Aliyu, Nurudeen Yusuf, Jamilu Mendelsohn, Laurel Coles, Wynona Danbauchi, Solomon Taylor, James Castro, Oswaldo Gordeuk, Victor R. Blackwelder, William C. Kato, Gregory J. Gladwin, Mark T. TI Pulmonary hypertension in adults and children with sickle cell disease in Nigeria: Prevalence, clinical characteristics and role of endemic tropical infections SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Aliyu, Zakari Y.; Castro, Oswaldo; Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Vandana, Sachdev; Mendelsohn, Laurel; Coles, Wynona; Taylor, James; Blackwelder, William C.; Kato, Gregory J.; Gladwin, Mark T.] NIH, NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Mamman, Aisha I.; Babadoko, Aliyu; Akpanpe, Peter; Attah, Ester; Suleiman, Yusuf; Aliyu, Nurudeen; Yusuf, Jamilu; Danbauchi, Solomon] Ahmadu Bello Univ Hosp, Zaria, Nigeria. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3793 BP 15B EP 15B PN 2 PG 1 WC Hematology SC Hematology GA 233OV UT WOS:000251101100049 ER PT J AU Cunha, AF Brugnerotto, AF Melo, MB Corat, MAF Gimenes, AP Passos, LAC Devlin, EE Bodine, DM Saad, STO Costa, FF AF Cunha, Anderson F. Brugnerotto, Ana F. Melo, Monica B. Corat, Marcus A. F. Gimenes, Ana P. Passos, Luiz A. C. Devlin, Emily E. Bodine, David M. Saad, Sara T. O. Costa, Fernando F. TI Expression of high levels of human gamma-globin in adult mice carrying a transgene of the Brazilian type of hereditary persistence of fetal hemoglobin SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Cunha, Anderson F.; Brugnerotto, Ana F.; Melo, Monica B.; Saad, Sara T. O.; Costa, Fernando F.] State Unicamp Campinas, UNICAMP, Hematol & Hemotherapy Ctr, Campinas, SP, Brazil. [Devlin, Emily E.; Bodine, David M.] NGHRI, Hematopoiesis Sect, Bethesda, MD USA. RI Corat, Marcus/M-2301-2013 OI Corat, Marcus/0000-0002-8801-2318 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3831 BP 26B EP 26B PN 2 PG 1 WC Hematology SC Hematology GA 233OV UT WOS:000251101100087 ER PT J AU Murphy, WJ Li, MH Panoskaltsis-Mortari, A Blazar, SR Sayers, TJ Nedospasov, S Taub, DD Welniak, LA Sun, K AF Murphy, William J. Li, Minghui Panoskaltsis-Mortari, Angela Blazar, SayersBruce R. Sayers, Thomas J. Nedospasov, Sergei Taub, Dennis D. Welniak, Lisbeth A. Sun, Kai TI Dissociating GVT from GVHD in murine BMT models through TNF alpha dependent CD4+ T cell mediated GVHD and IFN gamma dependent CD8+ T cell mediated anti-tumor effects SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Murphy, William J.; Li, Minghui; Welniak, Lisbeth A.; Sun, Kai] Univ Nevada, Reno, NV 89557 USA. [Panoskaltsis-Mortari, Angela; Blazar, SayersBruce R.] Univ Minnesota, Ctr Canc, Dept Pediat, Minneapolis, MN USA. [Sayers, Thomas J.] SAIC, Lab Expt Immunol, Frederick, MD USA. [Nedospasov, Sergei] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, Russia. [Taub, Dennis D.] NIA, Baltimore, MD 21224 USA. RI Nedospasov, Sergei/J-5936-2013; Sayers, Thomas/G-4859-2015; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 69 BP 29A EP 29A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800070 ER PT J AU Horman, SR Veto, CS Bourdeau, T Baktula, A Zhu, J Paul, W Jegga, A Caliguiri, MA Gebelein, B Grimes, HL AF Horman, Shane R. Veto, Chinamenveni S. Bourdeau, Tristan Baktula, Avinash Zhu, Jinfang Paul, William Jegga, Anil Caliguiri, Michael A. Gebelein, Brian Grimes, H. Leighton TI A conserved mechanism of transcription factor competition controls hematopoietic progenitor self-reinewal SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Horman, Shane R.; Veto, Chinamenveni S.; Bourdeau, Tristan; Baktula, Avinash; Jegga, Anil; Gebelein, Brian; Grimes, H. Leighton] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Zhu, Jinfang; Paul, William] NIAID, Bethesda, MD USA. [Caliguiri, Michael A.] OSUCCC, OSU, Columbus, OH USA. RI Nakafuku, Masato/J-3068-2013; Zhu, Jinfang/B-7574-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 91 BP 35A EP 36A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100800092 ER PT J AU Ornokaro, SO Ellison, FM Keyvanfar, K Chen, J Young, NS AF Ornokaro, Stephanie O. Ellison, Felicia M. Keyvanfar, Keyvan Chen, Jichun Young, Neal S. TI Utlilizing mutant mice to dissect immune bone marrow failure: Markedly reduced cytotoxicity of lymphocytes from Fas- and Fas ligand-deficient mice in lymph node cell-mediated aplastic anemia SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Ornokaro, Stephanie O.; Ellison, Felicia M.; Keyvanfar, Keyvan; Chen, Jichun; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3882 BP 38B EP 38B PN 2 PG 1 WC Hematology SC Hematology GA 233OV UT WOS:000251101100138 ER PT J AU Shin, DM Lee, CH Abbasi, S Morse, H AF Shin, Dong-Mi Lee, Chang Hoon Abbasi, Sadia Morse, Herbert TI Identification of transcriptional targets of IRF8 in germinal center B cells SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Shin, Dong-Mi; Lee, Chang Hoon; Abbasi, Sadia; Morse, Herbert] NIH, NIAID, Immunopathol Lab, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3884 BP 39B EP 39B PN 2 PG 1 WC Hematology SC Hematology GA 233OV UT WOS:000251101100140 ER PT J AU Cushman, M Larson, J Rosendaal, FR Phillips, LS Howard, BV Curb, JD Hays-Grudo, J Baird, A Eaton, CB Heckbert, SR Stafford, RS AF Cushman, Mary Larson, Joseph Rosendaal, Frits R. Phillips, Lawrence S. Howard, Barbara V. Curb, J. David Hays-Grudo, Jennifer Baird, Alison Eaton, Charles B. Heckbert, Susan R. Stafford, Randall S. TI Coagulation factors, postmenopausal hormone replacement therapy and the risk of venous thrombosis: The WHI clinical trials of postmenopausal hormone therapy SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Cushman, Mary] Med Univ Vermont, Burlington, VT USA. [Larson, Joseph] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Rosendaal, Frits R.] Leiden Univ, Leiden, Netherlands. [Phillips, Lawrence S.] Emory Univ, Atlanta, GA 30322 USA. [Howard, Barbara V.] MedStar Res Inst, Hyattsville, MD USA. [Curb, J. David] Univ Hawaii, Pacific Hlth Res Inst, Honolulu, HI 96822 USA. [Hays-Grudo, Jennifer] Texas A&M Univ, Temple, TX USA. [Baird, Alison] Natl Inst Hlth, Bethesda, MD USA. [Eaton, Charles B.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Heckbert, Susan R.] Univ Washington, Seattle, WA 98195 USA. [Stafford, Randall S.] Stanford Univ, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 127 BP 46A EP 46A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800128 ER PT J AU Lovely, RS Massaro, JF D'Agostino, RB Benjamin, EJ Kazmierczak, SC O'Donnell, CJ Farrell, DH AF Lovely, Rehana S. Massaro, Joseph F. D'Agostino, Ralph B., Sr. Benjamin, Eryielia J. Kazmierczak, Steven C. O'Donnell, Christopher J. Farrell, David H. TI Association of gamma ' fibrinogen with risk factors and prevalent cardiovascular disease in the framingham heart study SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Lovely, Rehana S.; Kazmierczak, Steven C.; Farrell, David H.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Massaro, Joseph F.; D'Agostino, Ralph B., Sr.; Benjamin, Eryielia J.; O'Donnell, Christopher J.] Natl Heart Lung & Blood Inst, Framingham, MA USA. [Massaro, Joseph F.; D'Agostino, Ralph B., Sr.; Benjamin, Eryielia J.] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 BP 47A EP 47A PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800132 ER PT J AU Dail, M Li, Q Lauchle, J McDaniel, A Kim, D Akagi, K Wolff, L Jenkins, N Copeland, N Shannon, K AF Dail, Monique Li, Qing Lauchle, Jennifer McDaniel, Andrew Kim, Doris Akagi, Keiko Wolff, Linda Jenkins, Nancy Copeland, Neil Shannon, Kevin TI Kras(G12D) expression in hematopoietic stem/progenitor cells initiates T cell acute lymphoblastic leukemia/lymphoma SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Dail, Monique; Li, Qing; Lauchle, Jennifer; McDaniel, Andrew; Kim, Doris; Shannon, Kevin] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Akagi, Keiko] Natl Canc Inst, Frederick, MD USA. [Wolff, Linda] Natl Canc Inst, Bethesda, MD USA. [Jenkins, Nancy; Copeland, Neil] Inst Mol & Cellular Biol, Singapore, Singapore. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 153 BP 52A EP 53A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100800154 ER PT J AU Dickinson, JD Pusic, I Rader, C Steinberg, S Hakim, F Baskar, S Pavietic, SZ AF Dickinson, John D. Pusic, Iskra Rader, Christoph Steinberg, Seth Hakim, Fran Baskar, Sivasubramanian Pavietic, Steven Z. TI Soluble BAFF is elevated following allogeneic SCT but is not an early predictor for the development of cGVHD SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Dickinson, John D.] Washington Univ, Sch Med, St Louis, MO USA. [Pusic, Iskra; Rader, Christoph; Hakim, Fran; Baskar, Sivasubramanian; Pavietic, Steven Z.] Natl Canc Inst, NIH, Expt Transplantat & Immunol Branch, Bethesda, MD USA. [Steinberg, Seth] Natl Canc Inst, Biostat & Data Management Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 167 BP 57A EP 57A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800168 ER PT J AU Hu, JQ Gomes, T Ferris, A Renaud, G Hendrie, PC Krouse, AE Donahue, RE Wolfsberg, TG Hughes, SH Russell, DW Dunbar, CE AF Hu, Jingqiong Gomes, Theotonius Ferris, Andrea Renaud, Gabriel Hendrie, Paul C. Krouse, Allen E. Donahue, Robert E. Wolfsberg, Tyra G. Hughes, Stephen H. Russell, David W. Dunbar, Cynthia E. TI Distinctive integration profile of avian sarcoma leukosis virus vectors in rhesus long-term repopulating cells SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Hu, Jingqiong; Gomes, Theotonius; Krouse, Allen E.; Donahue, Robert E.; Dunbar, Cynthia E.] NIH, NHLBI, Hematol Branch, Mol Hematopoiesis Sect, Bethesda, MD 20892 USA. [Ferris, Andrea; Hughes, Stephen H.] Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD USA. [Renaud, Gabriel; Wolfsberg, Tyra G.] NIH, NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Hendrie, Paul C.; Russell, David W.] Univ Washington, Dept Med, Div Hematol, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 198 BP 66A EP 66A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800199 ER PT J AU Sood, R English, M Belele, C Haskins, R Burnetti, A Chahal, J Liu, PP AF Sood, Raman English, Milton Belele, Christiane Haskins, Rebecca Burnetti, Anthony Chahal, Jagman Liu, Pu Paul TI Identification of three phases of hematopoieisis in zebrafish and their differential requirements for runx1 and gata1 functions SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Sood, Raman; English, Milton; Belele, Christiane; Haskins, Rebecca; Burnetti, Anthony; Chahal, Jagman; Liu, Pu Paul] NHGRI, NIH, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 202 BP 67A EP 67A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800203 ER PT J AU Li, XG Hu, X Felsenfeld, G Huang, SM AF Li, Xingguo Hu, Xin Felsenfeld, Gary Huang, Suming TI SF1 recruits hSET1 complex and is important for maintaining active chromatin domains in the beta-globin-locus SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Li, Xingguo; Hu, Xin; Huang, Suming] Univ Florida, Gainesville, FL 32611 USA. [Felsenfeld, Gary] NIDDK, NIH, Mol Biol Lab, Bethesda, MD USA. [Hu, Xin] Jilin Univ, Coll Life Sci, Changchun 130023, Peoples R China. [Huang, Suming] Univ Florida, Genet Inst, Gainesville, FL 32611 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 274 BP 88A EP 88A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800275 ER PT J AU Rezvani, K Yong, ASM Mielke, S Savani, BN Musse, L Superata, J Jafarpour, B Boss, C Barrett, AJ AF Rezvani, Katayoun Yong, Agnes S. M. Mielke, Stephan Savani, Bipin N. Musse, Laura Superata, Jeanine Jafarpour, Behnam Boss, Carol Barrett, A. John TI Leukemia-associated antigen specific T-Cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Rezvani, Katayoun; Yong, Agnes S. M.; Mielke, Stephan; Savani, Bipin N.; Musse, Laura; Superata, Jeanine; Jafarpour, Behnam; Boss, Carol; Barrett, A. John] NIH, NHLBI, Hematol Branch, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 287 BP 91A EP 92A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100800288 ER PT J AU Cokic, VP Beleslin-Cokic, BB Noguchi, CT Schechter, AN AF Cokic, Vladan P. Beleslin-Cokic, Bojana B. Noguchi, Constance Tom Schechter, Alan N. TI Globin genes induction by nitric oxide of stromal cell origin SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Cokic, Vladan P.] Inst Med Res, Lab Expt Hematol, Belgrade, Serbia. [Beleslin-Cokic, Bojana B.] Inst Endocrinol Diabet & Dis Metab, Belgrade, Serbia. [Noguchi, Constance Tom; Schechter, Alan N.] NIH, NIDDK, Mol Med Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 4102 BP 94B EP 94B PN 2 PG 1 WC Hematology SC Hematology GA 233OV UT WOS:000251101100358 ER PT J AU Lenz, G WrighT, G Dave, S Kohlmann, A Xiao, W Powell, J Zhao, H Xu, WL Gascoyne, RD Connors, JM May, L Weisenburger, DD Greiner, T Vose, J Armitage, JO Iqbal, J Bast, M Fu, K Campo, E Montserrat, E Lopez-Guillermo, A Jares, P Martinez, A Gibbs, B Rimsza, LM Fisher, RI Braziel, RM Tubbs, R Cook, J Pohlman, B Sweetenham, J Troen, G Smeland, EB Delabie, J Kvaloy, S Holte, H Jaffe, ES Wilson, WH Grant, N Hartmann, E Rosenwald, A Ott, G Muller-Hermelink, HK Lister, TA Williams, M Wicczorek, L Claim, WC Staudt, LM AF Lenz, Georg Wright, George Dave, Sandeep Kohlmann, Alexander Xiao, Wenming Powell, John Zhao, Hong Xu, Weiliong Gascoyne, Randy D. Connors, Joseph M. May, Lorraine Weisenburger, Dennis D. Greiner, Tim Vose, Julie Armitage, James O. Iqbal, Javeed Bast, Martin Fu, Kai Campo, Elias Montserrat, Emili Lopez-Guillermo, Armando Jares, Pedro Martinez, Antonio Gibbs, Betty Rimsza, Lisa M. Fisher, Richard I. Braziel, Rita M. Tubbs, Ray Cook, James Pohlman, Brad Sweetenham, John Troen, Gunhild Smeland, Erlend B. Delabie, Jan Kvaloy, Stein Holte, Harald Jaffe, Elaine S. Wilson, Wyndham H. Grant, Nicole Hartmann, Elena Rosenwald, Andreas Ott, Gentian Muller-Hermelink, Hans-Konrad Lister, T. Andrew Williams, Mickey Wicczorek, Lothar Claim, Wing C. Staudt, Louis M. TI Gene expression signatures predict overall survial in diffuse large B cell lymphoma treated with rituximab and chop-like chemotherapy SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Lenz, Georg; Wright, George; Dave, Sandeep; Xiao, Wenming; Powell, John; Zhao, Hong; Xu, Weiliong; Jaffe, Elaine S.; Wilson, Wyndham H.; Grant, Nicole; Staudt, Louis M.] NCI, CCR, Bethesda, MD 20892 USA. [Kohlmann, Alexander; Williams, Mickey; Wicczorek, Lothar] Roche Mol Syst Inc, Pleasanton, CA USA. [Gascoyne, Randy D.; Connors, Joseph M.; May, Lorraine] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Weisenburger, Dennis D.; Greiner, Tim; Vose, Julie; Armitage, James O.; Iqbal, Javeed; Bast, Martin; Fu, Kai] Univ Nebraska, Omaha, NE 68182 USA. [Campo, Elias; Montserrat, Emili; Lopez-Guillermo, Armando; Jares, Pedro; Martinez, Antonio] Univ Barcelona, Barcelona, Spain. [Gibbs, Betty; Rimsza, Lisa M.; Fisher, Richard I.; Braziel, Rita M.; Tubbs, Ray; Cook, James; Pohlman, Brad; Sweetenham, John] SW Oncol Grp, Seattle, WA USA. [Troen, Gunhild; Smeland, Erlend B.; Delabie, Jan; Kvaloy, Stein; Holte, Harald] Norwegian Radium Hosp, Oslo, Norway. [Hartmann, Elena; Rosenwald, Andreas; Ott, Gentian; Muller-Hermelink, Hans-Konrad] Univ Wurzburg, Wurzburg, Germany. [Lister, T. Andrew] St Barts Hosp, London, England. NR 0 TC 4 Z9 4 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 348 BP 109A EP 109A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800349 ER PT J AU Leich, E Salaverria, I Bea, S Zettl, A Gascoyne, RD Chan, WC Braziel, RM Rimsza, LM Weisenburger, DD Delabie, J Jaffe, ES Lister, TA Norton, AJ Staudt, LM Hartmann, EM Mueller-Hermelink, HK Campo, E Ott, G Rosenwald, A AF Leich, Ellen Salaverria, Itziar Bea, Silvia Zettl, Andreas Gascoyne, Randy D. Chan, Wing-Chung Braziel, Rita M. Rimsza, Lisa M. Weisenburger, Dennis D. Delabie, Jan Jaffe, Elaine S. Lister, Thomas A. Norton, Andrew J. Staudt, Louis M. Hartmann, Elena M. Mueller-Hermelink, Hans-Konrad Campo, Elias Ott, German Rosenwald, Andreas TI Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Leich, Ellen; Hartmann, Elena M.; Mueller-Hermelink, Hans-Konrad; Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. [Salaverria, Itziar; Bea, Silvia; Campo, Elias] Hosp Clin Barcelona, Dept Pathol, Barcelona, Spain. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [Braziel, Rita M.] Oregon Hlth & Sci Univ, SW Oncol Grp, Portland, OR 97201 USA. [Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ USA. [Delabie, Jan] Norwegian Radium Hosp, Oslo, Norway. [Jaffe, Elaine S.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Lister, Thomas A.; Norton, Andrew J.] St Bartholomews Hosp, Canc Res UK, London, England. [Staudt, Louis M.] NCI, Metab Branch, Bethesda, MD 20892 USA. [Ott, German] Robert Bosch Krankenhaus, Inst Clin Pathol, Stuttgart, Germany. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 360 BP 113A EP 113A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800361 ER PT J AU Chung, YJ Choi, CW Slape, C Fry, T Aplan, PD AF Chung, Yang Jo Choi, Chul Won Slape, Christopher Fry, Terry Aplan, Peter D. TI A NUP98-HOXD13 fusion gene induces a transplantable myelodysplastic syndrome in mice SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Chung, Yang Jo; Choi, Chul Won; Slape, Christopher; Fry, Terry; Aplan, Peter D.] NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Chung, Yang Jo; Choi, Chul Won; Slape, Christopher; Fry, Terry; Aplan, Peter D.] NCI, NIH, Ctr Canc Res, Pediat Oncol Branch, Bethesda, MD 20892 USA. RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016 OI Slape, Christopher/0000-0002-8407-3092; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 BP 125A EP 125A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800402 ER PT J AU Farrar, J Nater, M Caywood, E McDevitt, M Kowalski, J Takemoto, C Talbot, C Meltzer, P Esposito, D Beggs, A Schneider, H Grabowska, A Ball, S Niewiadomska, E Sieff, C Vlachos, A Atsidaftos, E Ellis, S Lipton, J Gazda, H Arceci, RJ AF Farrar, Jason Nater, Michelle Caywood, Emi McDevitt, Michael Kowalski, Jeanne Takemoto, Clifford Talbot, Connie Meltzer, Paul Esposito, Diane Beggs, Alan Schneider, Hal Grabowska, Agnieszka Ball, Sarah Niewiadomska, Edyta Sieff, Colin Vlachos, Adrianna Atsidaftos, Eva Ellis, Steven Lipton, Jeffrey Gazda, Hanna Arceci, Robert J. TI A large ribosomal subunit protein abnormality in diamond-blackfan anemia (DBA) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Farrar, Jason; Nater, Michelle; Caywood, Emi; McDevitt, Michael; Kowalski, Jeanne; Takemoto, Clifford; Talbot, Connie; Arceci, Robert J.] Johns Hopkins Univ Hosp, Baltimore, MD USA. [Meltzer, Paul] NIH, Bethesda, MD 20892 USA. [Beggs, Alan] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. [Ball, Sarah] St Georges Univ London, London, England. [Niewiadomska, Edyta] Univ Med Sch, Warsaw, Poland. [Vlachos, Adrianna; Atsidaftos, Eva; Lipton, Jeffrey] Albert Einstein Coll Med, New Hyde Pk, NY USA. [Ellis, Steven] Univ Louisville, Louisville, KY 40292 USA. [Esposito, Diane] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 422 BP 131A EP 131A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800423 ER PT J AU Vichinsky, E Gold, J Rule, R Weiner, M Eggleston, B Muma, A Neumayr, L Lieff, S Bessman, D Kalinyak, K De Castro, L Harrington, T Hussein, A Johnson, C McMahon, L Orringer, E Rutherford, C Armstrong, D AF Vichinsky, Elliott Gold, J. Rule, R. Weiner, M. Eggleston, B. Muma, A. Neumayr, L. Lieff, S. Bessman, D. Kalinyak, K. De Castro, L. Harrington, T. Hussein, A. Johnson, C. McMahon, L. Orringer, E. Rutherford, C. Armstrong, D. CA Comprehens Sickle Cell Ctr TI Neuropsychological (NP) dysfunction and neuroimaging abnormalities in neurologically intact adult patients with sickle cell disease (SCD) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Gold, J.; Johnson, C.] Univ So Calif, Los Angeles, CA 90089 USA. [Rule, R.; Weiner, M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Eggleston, B.; Muma, A.; Lieff, S.] Univ Technol Sydney, Sydney, NSW, Australia. [McMahon, L.] Boston Med Ctr, Boston, MA USA. [Orringer, E.] Univ N Carolina, Chapel Hill, NC 27515 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 428 BP 132A EP 133A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100800429 ER PT J AU Delmonte, J Kantarjian, HM Garcia-Manero, G Estrov, Z Ravandi, F Verstovsek, S O'Brien, S Koller, CA Faderl, S Thomas, DA Wright, JJ Cortes, J AF Delmonte, John, Jr. Kantarjian, Hagop M. Garcia-Manero, Guillermo Estrov, Zeev Ravandi, Farhad Verstovsek, Srdan O'Brien, Susan Koller, Charles A. Faderl, Stefan Thomas, Deborah A. Wright, John J. Cortes, Jorge TI Final update of phase I-II study of the farnesyltransferase inhibitor tipifarnib in combination with idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Delmonte, John, Jr.; Kantarjian, Hagop M.; Garcia-Manero, Guillermo; Estrov, Zeev; Ravandi, Farhad; Verstovsek, Srdan; O'Brien, Susan; Koller, Charles A.; Faderl, Stefan; Thomas, Deborah A.; Cortes, Jorge] Univ Texas MD Anderson Canc Ctr Houston, Houston, TX USA. [Wright, John J.] Natl Inst Hlth, Investigat Drug Branch, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 441 BP 136A EP 136A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800442 ER PT J AU Morisot, S Hildreth, R Kaplan, IM Stetler-Stevenson, M Taylor, JA Ahuja, Y Bloom, L Wayne, AS Civin, CI AF Morisot, Sebastien Hildreth, Richard Kaplan, Ian M. Stetler-Stevenson, Maryalice Taylor, Julie A. Ahuja, Yachna Bloom, Lauren Wayne, Alan S. Civin, Curt I. TI Sensitive NOD-scid-IL2 gamma(null) (NOG-scid) assay for human precursor B acute lymphoblastic leukemias (ALL) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Morisot, Sebastien; Hildreth, Richard; Kaplan, Ian M.; Taylor, Julie A.; Bloom, Lauren; Civin, Curt I.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Div Immunol & Hematopoiesis, Baltimore, MD USA. [Stetler-Stevenson, Maryalice] NIH, Natl Canc Inst, Canc Res Ctr, Pathol Lab, Bethesda, MD USA. [Ahuja, Yachna; Wayne, Alan S.] NIH, Natl Canc Inst, Canc Res Ctr, Pediat Oncol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 4286 BP 139B EP 139B PN 2 PG 1 WC Hematology SC Hematology GA 233OV UT WOS:000251101101057 ER PT J AU Kamikubo, Y Garrett-Beat, L Liu, PP AF Kamikubo, Yasuhiko Garrett-Beat, Lisa Liu, Pu Paul TI Leukemogenesis by truncated CBF beta-SMMHC defective in repressing RUNX1 SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Kamikubo, Yasuhiko; Garrett-Beat, Lisa; Liu, Pu Paul] NIH, NHGRI, Genet & Mol Biol Branch, Bethesda, MD USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 462 BP 142A EP 142A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800463 ER PT J AU Sokolic, R Podsakoff, G Muul, L Engel, B Jagadeesh, J Garabedian, E Carbonaro, D Tuschong, L Ireland, J Hershfield, M Tisdale, J Dunbar, C Wayne, A Kohn, D Candotti, F AF Sokolic, Robert Podsakoff, Greg Muul, Linda Engel, Barbara Jagadeesh, Jayashree Garabedian, Elizabeth Carbonaro, Denise Tuschong, Laura Ireland, Joanna Hershfield, Michael Tisdale, John Dunbar, Cynthia Wayne, Alan Kohn, Donald Candotti, Fabio TI Comparative results of gene therapy for adenosine deaminase deficiency with or without PEG-ADA withdrawal and myelosuppressive chemotherapy SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Sokolic, Robert; Muul, Linda; Jagadeesh, Jayashree; Garabedian, Elizabeth; Candotti, Fabio] Natl Human Genome Res Inst, Bethesda, MD USA. [Podsakoff, Greg; Engel, Barbara; Carbonaro, Denise; Ireland, Joanna; Kohn, Donald] Childrens Hosp Los Angeles, Los Angeles, CA USA. [Tuschong, Laura; Wayne, Alan] NCI, Bethesda, MD 20892 USA. [Hershfield, Michael] Duke Univ, Ctr Med, Durham, NC 27706 USA. [Tisdale, John] NIDDK, Bethesda, MD 20892 USA. [Dunbar, Cynthia] NHLBI, Bethesda, MD USA. RI Sokolic, Robert/I-6072-2012 NR 0 TC 2 Z9 2 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 501 BP 154A EP 154A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800502 ER PT J AU Kang, EM Linton, G Tbeobald, N O'Brien, SA Hilligoss, D Malech, HL AF Kang, Elizabeth M. Linton, Gilda Tbeobald, Narda O'Brien, Sandra Anaya Hilligoss, Dianne Malech, Harry L. TI Treatment of infections in patients with X-linked Chronic Granulomatous Disease (XCGD) with gene therapy SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Kang, Elizabeth M.; Linton, Gilda; Tbeobald, Narda; O'Brien, Sandra Anaya; Hilligoss, Dianne; Malech, Harry L.] NIAID, NIH, LHD, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 504 BP 155A EP 155A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800505 ER PT J AU O'Mahony, D Bernstein, W Wyvill, K Aleman, K Whitby, D Steinberg, S Tosato, G Pittaluga, S Jaffe, ES Yarchoan, R Little, RF AF O'Mahony, Deirdre Bernstein, Wendy Wyvill, Kathy Aleman, Karen Whitby, Denise Steinberg, Seth Tosato, Giovanna Pittaluga, Stefania Jaffe, Elaine S. Yarchoan, Robert Little, Richard F. TI Early results of a clinical trial using targeted oncolytic virotherapy in, Kaposi sarcoma herpes virus (KSHV) associated multicentric Castleman's disease (MCD) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [O'Mahony, Deirdre; Bernstein, Wendy; Wyvill, Kathy; Aleman, Karen; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. [Whitby, Denise] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Steinberg, Seth] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Tosato, Giovanna] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Lab Pathol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 514 BP 158A EP 158A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800515 ER PT J AU Lauchle, JO Le, DT Kim, D Akagi, K Gorman, MF Tran, M Sebolt-Leopold, J Wolff, L Parada, LF Jenkins, N Copeland, N Shannon, KM AF Lauchle, Jennifer O. Le, Doan T. Kim, Doris Akagi, Keiko Gorman, Matthew F. Tran, Mary Sebolt-Leopold, Judith Wolff, Linda Parada, Luis F. Jenkins, Nancy Copeland, Neal Shannon, Kevin M. TI Mutations that cooperate with Nf1 inactivation in leukemogenesis influence therapeutic response to MEK inhibition SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Lauchle, Jennifer O.; Kim, Doris; Gorman, Matthew F.; Tran, Mary; Shannon, Kevin M.] Univ Calif San Francisco, San Francisco, CA USA. [Le, Doan T.] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Akagi, Keiko] Natl Inst Hlth, Natl Canc Inst, Frederick, MD USA. [Sebolt-Leopold, Judith] Pfizer, Res & Dev, Ann Arbor, MI USA. [Wolff, Linda] Natl Canc Inst, Bethesda, MD USA. [Parada, Luis F.] Univ Texas, Dallas, TX USA. RI Parada, luis/B-9400-2014 NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 594 BP 183A EP 183A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800595 ER PT J AU Vinogradova, YE Lutsenko, IN Samoilova, RS Kaplanskaya, IB Vorobiev, IA Zingerman, BV Rijicova, NB Shklovskiy-Kordi, NE Giliazitdinova, EA Margolin, OV Maryin, DC Krementskaya, A Kravehenko, SK Varticovski, L Vorobiev, AI AF Vinogradova, Yulia E. Lutsenko, I. N. Samoilova, R. S. Kaplanskaya, I. B. Vorobiev, Ivan A. Zingerman, Boris V. Rijicova, N. B. Shklovskiy-Kordi, Nikita E. Giliazitdinova, E. A. Margolin, Oleg V. Maryin, D. C. Krementskaya, Alexandra Kravehenko, S. K. Varticovski, Lyuba Vorobiev, Andrei I. TI Classification and survival of 179 patients with T- and NK-Cell lymphomas at the Federal Research Hematology Center of Russian Academy of Medical Sciences: A retrospective study SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Vinogradova, Yulia E.; Lutsenko, I. N.; Samoilova, R. S.; Kaplanskaya, I. B.; Vorobiev, Ivan A.; Zingerman, Boris V.; Rijicova, N. B.; Shklovskiy-Kordi, Nikita E.; Giliazitdinova, E. A.; Margolin, Oleg V.; Maryin, D. C.; Krementskaya, Alexandra; Kravehenko, S. K.; Vorobiev, Andrei I.] Russian Acad Med Sci, Fed Res Hematol, Dept Chemotherapy Hematol Dis & Intens Therapy, Moscow, Russia. [Varticovski, Lyuba] Ctr Canc Res, NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 4461 BP 185B EP 185B PN 2 PG 1 WC Hematology SC Hematology GA 233OV UT WOS:000251101101232 ER PT J AU Nemeth, M Yang, Y Bodine, D AF Nemeth, Michael Yang, Yingzi Bodine, David TI beta-catenin expression in bone marrow stromal cells is required for normal proliferation and differentiation of primitive hematopoietic cells SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Nemeth, Michael; Yang, Yingzi; Bodine, David] NHGRI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 608 BP 188A EP 188A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800609 ER PT J AU Weksberg, DC Feng, CG Sher, A Goodell, MA AF Weksberg, David C. Feng, Carl G. Sher, Alan Goodell, Margaret A. TI The P47 GTPase Lrg-47 links host defense and HSC proliferation SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Weksberg, David C.; Feng, Carl G.; Goodell, Margaret A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Weksberg, David C.; Goodell, Margaret A.] Natl Inst Allergy & Infect Dis, Immunol Sect, Parasit Dis Lab, Bethesda, MD USA. [Weksberg, David C.; Goodell, Margaret A.] Baylor Coll Med, Stem Cell & Regenerat Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 640 BP 197A EP 197A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800641 ER PT J AU Landgren, O Kristinsson, SY Goldin, LR Caporaso, NE Blimark, C Mellqvist, UH Wahlin, A Bjorkholm, M Turesson, I AF Landgren, Ola Kristinsson, Sigurdur Y. Goldin, Lynn R. Caporaso, Neil E. Blimark, Cecilie Mellqvist, Ulf-Henrik Wahlin, Anders Bjorkholm, Magnus Turesson, Ingemar TI Increased risk of monoclonal gammopathy of undetermined significance (MGUS) and lymphoproliferative tumors among 14689 first-degree relatives of 4488 MGUS patients in Sweden SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Landgren, Ola; Goldin, Lynn R.; Caporaso, Neil E.; Blimark, Cecilie] Natl Inst Hlth, Natl Canc Inst, Bethesda, MD USA. [Landgren, Ola; Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Univ Hosp & Inst, Hematol Ctr, Dept Med, Stockholm, Sweden. [Blimark, Cecilie; Mellqvist, Ulf-Henrik] Sahlgrens Univ Hosp, Dept Med, Sect Hematol & Coagulat, S-41345 Gothenburg, Sweden. [Wahlin, Anders] Univ Umea Hosp, Hematol Sect, S-90185 Umea, Sweden. [Turesson, Ingemar] Malmo Univ Hosp, Dept Med, Hematol Sect, Malmo, Sweden. RI Wahlin, Anders/F-6043-2013; Kristinsson, Sigurdur /M-2910-2015 OI Wahlin, Anders/0000-0001-6402-0463; Kristinsson, Sigurdur /0000-0002-4964-7476 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 660 BP 203A EP 203A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800661 ER PT J AU Landgren, O Goldin, LR Kristinsson, SY Samuelsson, J Bjorkholm, M AF Landgren, Ola Goldin, Lynn R. Kristinsson, Sigurdur Y. Samuelsson, Jan Bjorkholm, Magnus TI Increased risks of polycythemia vera (PV), essential Thrombocythemia (ET), and myelofibrosis (MF) among 24577 first-degree relatives of 11039 patients with chronic myeloproliferative disorders (MPD) in sweden. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Landgren, Ola; Goldin, Lynn R.] Natl Canc Inst, NIH, Bethesda, MD USA. [Landgren, Ola; Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Univ Hosp & Inst, Dept Med, Hematol Ctr, Stockholm, Sweden. [Samuelsson, Jan] Stockholm S Hosp, Dept Med, Stockholm, Sweden. RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 680 BP 209A EP 209A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800681 ER PT J AU Calvo, KR Dabir, B Bandle, R Bond, A Jaffe, ES AF Calvo, Katherine R. Dabir, Bhavana Bandle, Russell Bond, Amelia Jaffe, Elaine S. TI IL-4 expression and constitutive activation of erk signaling in vivo in follicular lymphoma. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Calvo, Katherine R.; Dabir, Bhavana; Bandle, Russell; Bond, Amelia; Jaffe, Elaine S.] Natl Canc Inst, Pathol Lab, Bethesda, MD USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 687 BP 211A EP 212A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100800688 ER PT J AU Lenz, G Davis, RE Ngo, VN Lam, LT George, T Wright, GW Dave, SS Zhao, H Xu, W Rosenwald, A Muller-Hermelink, HK Gascoyne, RD Connors, JM Campo, E Jaffe, ES Delabie, J Smeland, EB Rimsza, L Fisher, RI Chan, WC Staudt, LM AF Lenz, Georg Davis, R. Eric Ngo, Vu N. Lam, Lloyd T. George, Thaddeus Wright, George W. Dave, Sandeep S. Zhao, Hong Xu, Weihong Rosenwald, Andreas Muller-Hermelink, Hans-Konrad Gascoyne, Randy D. Connors, Joseph M. Campo, Elias Jaffe, Elaine S. Delabie, Jan Smeland, Eriend B. Rimsza, Lisa Fisher, Richard I. Chan, Wing C. Staudt, Louis M. TI CARD11 as an oncogene in diffuse large B cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Lenz, Georg; Davis, R. Eric; Ngo, Vu N.; Lam, Lloyd T.; Wright, George W.; Dave, Sandeep S.; Zhao, Hong; Xu, Weihong; Jaffe, Elaine S.; Staudt, Louis M.] Ctr Canc Res, NCI, Bethesda, MD USA. [George, Thaddeus; Muller-Hermelink, Hans-Konrad] Amnis Corp, Seattle, WA USA. [Rosenwald, Andreas] Univ Wurzburg, D-97070 Wurzburg, Germany. [Gascoyne, Randy D.; Connors, Joseph M.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Campo, Elias] Univ Barcelona, E-08007 Barcelona, Spain. [Delabie, Jan; Smeland, Eriend B.] Norwegian Radium Hosp, Oslo, Norway. [Rimsza, Lisa] Univ Arizona, Tucson, AZ 85721 USA. [Chan, Wing C.] Univ Nebraska, Lincoln, NE 68583 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 692 BP 213A EP 213A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100800693 ER PT J AU Anderson, LA Pfeiffer, RM Rapkin, JS Gridley, G Mellemkjaer, L Hemminki, K Bjorkholm, M Goldin, LR Caporaso, NE Langren, C AF Anderson, Lesley A. Pfeiffer, Ruth M. Rapkin, Joshua S. Gridley, Gloria Mellemkjaer, Lene Hemminki, Kari Bjorkholm, Magnus Goldin, Lynn R. Caporaso, Neil E. Langren, Cila TI Survival patterns among chronic lymphocytic leukemia and other lymphoma patients with family history of lymphoma SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Anderson, Lesley A.; Pfeiffer, Ruth M.; Rapkin, Joshua S.; Gridley, Gloria; Goldin, Lynn R.; Caporaso, Neil E.; Langren, Cila] NIH, Natl Canc Inst, Bethesda, MD 20892 USA. [Mellemkjaer, Lene] Inst Canc Epidemiol, Danish Canc Inst, Copenhagen, Denmark. [Hemminki, Kari] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany. [Hemminki, Kari] Karolinska Inst, Ctr Family Med, Huddinge, Sweden. [Bjorkholm, Magnus] Karolinska Univ Hosp, Hematol Ctr, Karolinska Inst, Dept Med, Stockholm, Sweden. RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 4683 BP 244B EP 244B PN 2 PG 1 WC Hematology SC Hematology GA 233OV UT WOS:000251101101454 ER PT J AU Cichocki, FM Lenvik, T Anderson, SK Miller, JS AF Cichocki, Frank M. Lenvik, Todd Anderson, Stephen K. Miller, Jeffrey S. TI STAT5A overexpression enhances killer immunoglobulin receptor (KIR) expression in developing NK cells and is associated with a loss of reverse transcription from the proximal KIR promoter SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Cichocki, Frank M.; Lenvik, Todd; Miller, Jeffrey S.] Univ Minnesota, Blood & Marrow Transplant Program, Div Hematol Oncol & Transplantat, Minneapolis, MN USA. [Anderson, Stephen K.] SAIC Frederick Inc, Natl Canc Inst, Basic Res Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 798 BP 245A EP 245A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801067 ER PT J AU Sloand, EM Pfannes, L Reddy, R Reddy, P Groopman, JS Young, NS AF Sloand, Elaine M. Pfannes, Loretta Reddy, Rantana Reddy, Premkumar Groopman, Jerome S. Young, Neal S. TI Suppression of cyclin D1 by on 01910.Na is associated with decreased survival of trisomy 8 myelodyplastic bone marrow progenitors: A potential targetted therapy SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Sloand, Elaine M.; Pfannes, Loretta; Groopman, Jerome S.; Young, Neal S.] NHLBI, Div Intramural Res, Hematol Branch, Bethesda, MD 20892 USA. [Reddy, Rantana; Reddy, Premkumar] Oncol Therapeuts, Lawrenceville, NJ USA. [Groopman, Jerome S.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 822 BP 252A EP 252A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801091 ER PT J AU Bergerson, RJ Collier, LS Allaei, R Silverstein, KA Lamblin, AFF Wolff, L Kogan, SC Kersey, JH Adams, DJ Largaespada, DA AF Bergerson, Rachel J. Collier, Lara S. Allaei, Raha Silverstein, Kevin A. Lamblin, Anne-Francoise F. Wolff, Linda Kogan, Scott C. Kersey, John H. Adams, David J. Largaespada, David A. TI Novel Mll-AF9 cooperating genes identified in a leukemogenesis screen using retroviral mutagenesis SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Bergerson, Rachel J.; Collier, Lara S.; Allaei, Raha; Kersey, John H.; Largaespada, David A.] Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. [Silverstein, Kevin A.; Lamblin, Anne-Francoise F.] Univ Minnesota, Canc Ctr Bioinformat Shared Resource, Minneapolis, MN 55455 USA. [Wolff, Linda] Ctr Canc Res, Natl Canc Inst, Bethesda, MD USA. [Kogan, Scott C.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Kogan, Scott C.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Adams, David J.] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 825 BP 253A EP 253A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801094 ER PT J AU Reganti, S Kabba, E Stock, W Wright, JJ Godwin, JE Kini, AR AF Reganti, Sowianya Kabba, Edith Stock, Wendy Wright, John J. Godwin, John E. Kini, Ameet R. TI Anti-angiogenic effects of sorafenib in relapsed chronic lymphocytic leukemia: Correlative studies of a phase 2 clinical trial SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Reganti, Sowianya; Kabba, Edith; Kini, Ameet R.] Loyola Univ, Cardinal Bernardin Canc Ctr, Chicago Stritch Sch Med, Maywood, IL USA. [Stock, Wendy] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Wright, John J.] Natl Canc Inst, CTEP, Rockville, MD USA. [Godwin, John E.] Univ Illinois, Sch Med, Dept Med, Div Hematol Oncol, Springfield, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 4726 BP 255B EP 255B PN 2 PG 1 WC Hematology SC Hematology GA 233OV UT WOS:000251101102018 ER PT J AU Savage, SA Giri, N Baerlocher, GM Orr, N Lansdorp, PM Alter, BP AF Savage, Sharon A. Giri, Neelam Baerlocher, Gabriela M. Orr, Nick Lansdorp, Peter M. Alter, Blanche P. TI TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Savage, Sharon A.; Giri, Neelam; Alter, Blanche P.] NCI, NIH, DCEG, Rockville, MD USA. [Orr, Nick] NCI, NIH, CCR, Rockville, MD USA. [Baerlocher, Gabriela M.] Univ Hosp Bern, CH-3010 Bern, Switzerland. [Baerlocher, Gabriela M.; Lansdorp, Peter M.] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 835 BP 256A EP 256A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801104 ER PT J AU Bessler, M Schrezenmeier, H Maciejewski, JP Hill, A Rollins, SA Young, NS Luzzatto, L AF Bessler, Monica Schrezenmeier, Hubert Maciejewski, Jaroslaw P. Hill, Anita Rollins, Scott A. Young, Neal S. Luzzatto, Lucio TI Significant disease burden in paroxysmal nocturnal hemoglobinuria patients with lower levels of hemolysis, mild anemia and minimal transfusion: Clinical improvement with eculizumab therapy. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Bessler, Monica] Washington Univ, Sch Med, St Louis, MO USA. [Schrezenmeier, Hubert] Inst Clin Transfus Med & Immunogenet, Ulm, Germany. [Maciejewski, Jaroslaw P.] Cleveland Clin, Cleveland, OH 44106 USA. [Hill, Anita] Gen Infirm, Leeds LS1 3EX, W Yorkshire, England. [Rollins, Scott A.] Alexion Pharmaceut, Cheshire, CT USA. [Young, Neal S.] NHLBI, Bethesda, MD 20892 USA. [Luzzatto, Lucio] Ist Toscano Tumori, Florence, Italy. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 840 BP 257A EP 258A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801109 ER PT J AU Hsieh, MM Link, B Machado, R Kato, G Gladwin, M Tisdale, JF AF Hsieh, Matthew M. Link, Beth Machado, Roberto Kato, Gregory Gladwin, Mark Tisdale, John F. TI Improvement in hemolytic parameters and tricuspid regurgitant jet velocity (TRV) following non-myeloablative allogeneic stem cell transplantation (allo-SCT) in adults with severe sickle cell-disease (SCD) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Hsieh, Matthew M.; Link, Beth; Tisdale, John F.] NIDDK, NIH, MCHB, Bethesda, MD 20892 USA. [Machado, Roberto; Kato, Gregory; Gladwin, Mark] NIH, NHLBI, VMB, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 843 BP 258A EP 259A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801112 ER PT J AU Hsu, LL Shiva, S Noguchi, A Curtis, E MacArthur, P Raat, NJH Diwan, BA Schechter, AN Noguchi, CT Gladwin, MT AF Hsu, Lewis L. Shiva, Sruti Noguchi, Audrey Curtis, Erin MacArthur, Peter Raat, Nicolaas J. H. Diwan, Bhalchandra A. Schechter, Alan N. Noguchi, Constance Tom Gladwin, Mark T. TI Depletion and restoration of the intravascular nitrite (NO2-) reserve modulate susceptibility to liver vaso-occlusive-infarction in sickle cell trasgenic mice SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Hsu, Lewis L.] St Christophers Hosp Children, Marian Anderson Sickle Cell Ctr, Philadelphia, PA 19133 USA. [Hsu, Lewis L.; Shiva, Sruti; Curtis, Erin; MacArthur, Peter; Raat, Nicolaas J. H.; Gladwin, Mark T.] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Hsu, Lewis L.; Noguchi, Audrey; Schechter, Alan N.; Noguchi, Constance Tom] Natl Inst Diabetes Digest & Kidney Disorders, Bethesda, MD USA. [Diwan, Bhalchandra A.] NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 841 BP 258A EP 258A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801110 ER PT J AU Ammosova, T Xu, M Nekhai, S Kato, GJ Gladwin, MT Castro, OL Gordeuk, VR AF Ammosova, Tatyana Xu, Min Nekhai, Sergei Kato, Gregory J. Gladwin, Mark T. Castro, Oswaldo L. Gordeuk, Victor R. TI Detection of the mRNA transcription level of several genes of the HIF and NO metabolic pathways in PBMCs of sickle cell disease patients using quantitative RT-PCR assay SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Ammosova, Tatyana; Xu, Min; Nekhai, Sergei; Castro, Oswaldo L.; Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Kato, Gregory J.; Gladwin, Mark T.] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 844 BP 259A EP 259A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801113 ER PT J AU Wayne, AS Findley, HW Lew, G Ahuja, Y Gu, L Stetler-Stevenson, M Kreitman, RJ Pastan, I AF Wayne, Alan S. Findley, Harry W. Lew, Glen Ahuja, Yachna Gu, Lubing Stetler-Stevenson, Maryalice Kreitman, Robert J. Pastan, Ira TI Targeting CD22 in childhood B-precursor acute lymphoblastic leukemia (pre-B ALL): Pre-clinical studies and Phase I trial of the anti-CD22 immunotoxin CAT-3888 (BL22). SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Wayne, Alan S.; Ahuja, Yachna] NCI, NIH, Ctr Canc Res, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Ahuja, Yachna; Kreitman, Robert J.; Pastan, Ira] NCI, NIH, Ctr Canc Res, Mol Biol Lab, Bethesda, MD 20892 USA. [Stetler-Stevenson, Maryalice] NCI, NIH, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. [Lew, Glen; Gu, Lubing] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Aflac Canc Ctr Blood Disorders Serv, Atlanta, GA 30322 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 855 BP 262A EP 262A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801124 ER PT J AU Ahuja, Y Stetler-Stevenson, M Kreitman, RJ Pastan, I Wayne, AS AF Ahuja, Yachna Stetler-Stevenson, Maryalice Kreitman, Robert J. Pastan, Ira Wayne, Alan S. TI Pre-clinical evaluation of the anti-CD22 immunotoxin CAT-8015 in combination with chemotherapy agents for childhood B-precursor acute lymphoblastic leukemia (pre-B ALL). SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Ahuja, Yachna; Wayne, Alan S.] NCI, NIH, Ctr Canc Res, Pediat Oncol Branch, Bethesda, MD USA. [Ahuja, Yachna; Kreitman, Robert J.; Pastan, Ira] NCI, NIH, Ctr Canc Res, Lab Mol Biol, Bethesda, MD USA. [Stetler-Stevenson, Maryalice] NCI, NIH, Ctr Canc Res, Pathol Lab, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 865 BP 265A EP 265A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801134 ER PT J AU Delmonte, J Kantarjian, HM Andreef, M Faderl, S Wright, JJ Zhang, W Konopleva, M Verstovsek, S Borthakur, G Ravandi, F Cortes, J AF Delmonte, John, Jr. Kantarjian, Hagop M. Andreef, Michael Faderl, Stefan Wright, John J. Zhang, Weiguo Konopleva, Marina Verstovsek, Srdan Borthakur, Gautam Ravandi, Farhad Cortes, Jorge TI Update of a phase I study of sorafenib in patients with refractory/relapsed acute myeloid leukemia or high-risk myelodysplastic syndrome SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Delmonte, John, Jr.; Kantarjian, Hagop M.; Andreef, Michael; Faderl, Stefan; Zhang, Weiguo; Konopleva, Marina; Verstovsek, Srdan; Borthakur, Gautam; Ravandi, Farhad; Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Wright, John J.] NIH, Invest Drug Branch, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 893 BP 272A EP 273A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801162 ER PT J AU Kirschbaum, MH Stein, AS Tuscano, J Zain, JM Popplewell, L O'Donnell, MR Karanes, C Wright, J Pulone, B Rincon, A Frankel, P Forman, SJ Newman, E AF Kirschbaum, Mark H. Stein, Anthony Selwyn Tuscano, Joseph Zain, Jasmine M. Popplewell, Leslie O'Donnell, Margaret R. Karanes, Chatchada Wright, John Pulone, Bernadette Rincon, Amalia Frankel, Paul Forman, Stephen. J. Newman, Edward TI A phase I study of the farnesyltransferase inhibitor tipifarnib in a week-on week-off dose schedule in acute myelogenous leukemia SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Kirschbaum, Mark H.; Stein, Anthony Selwyn; Zain, Jasmine M.; Popplewell, Leslie; O'Donnell, Margaret R.; Karanes, Chatchada; Pulone, Bernadette; Rincon, Amalia; Frankel, Paul; Forman, Stephen. J.; Newman, Edward] City Hope Natl Canc Ctr, Duarte, CA USA. [Tuscano, Joseph] Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. [Wright, John] NCI, CTEP, Invest Drug Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 891 BP 272A EP 272A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801160 ER PT J AU Yee, KWL Minden, MD Brandwein, J Schimmer, A Schuh, A Gupta, V Messner, HA Foley, R Wasi, P Zwiebel, JA Leber, B AF Yee, Karen W. L. Minden, Mark D. Brandwein, Joseph Schimmer, Aaron Schuh, Andre Gupta, Vikas Messner, Hans A. Foley, Ronan Wasi, Parven Zwiebel, James A. Leber, Brian TI A phase I trial of two sequence-specific schedules of decitabine and vorinostat in patients with acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Yee, Karen W. L.; Minden, Mark D.; Brandwein, Joseph; Schimmer, Aaron; Schuh, Andre; Gupta, Vikas; Messner, Hans A.] Univ Hlth Network, Princess Margaret Hosp, Toronto, ON, Canada. [Foley, Ronan; Wasi, Parven; Leber, Brian] Hamilton Hlth Sci, Div Hematol, Hamilton, ON, Canada. [Zwiebel, James A.] NCI, NIH, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 908 BP 277A EP 277A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801177 ER PT J AU Ricklis, RM Karp, JE Feldman, EJ Galkin, S Greer, JM Ironside, V Mirjafary, K Talbot, TD Morris, LE Wright, JJ Kaufmann, SH AF Ricklis, Rebecca M. Karp, Judith E. Feldman, Eric J. Galkin, Suzanne Greer, Jacqueline M. Ironside, Valerie Mirjafary, Kirn Talbot, Timothy D. Morris, Lawrence E. Wright, John J. Kaufmann, Scott H. TI In vivo correlates of response for phase I trial of oral tipifarnib (T) combined with oral etoposide (E) for adults age >= 70 with newly diagnosed acute myelogenous leukemia (AML) who are not candidates for traditional cytotoxic chemotherapy (TCC). SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Ricklis, Rebecca M.; Karp, Judith E.; Galkin, Suzanne; Greer, Jacqueline M.; Ironside, Valerie] Johns Hopkins Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Feldman, Eric J.; Talbot, Timothy D.] Cornell Univ, NY Presbyterian Hosp, New York, NY USA. [Morris, Lawrence E.] Bone Marrow Transplant Grp Georgia, Atlanta, GA USA. [Mirjafary, Kirn; Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Kaufmann, Scott H.] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 914 BP 278A EP 279A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801183 ER PT J AU Buadi, F Katzmann, JA Pfeiffer, RM Hsing, AW Yeboah, ED Biritwum, RB Dispenzieri, A Kyle, R Rajkumar, V Landgren, O AF Buadi, Francis Katzmann, Jerry A. Pfeiffer, Ruth M. Hsing, Ann W. Yeboah, Edward D. Biritwum, Richard B. Dispenzieri, Angela Kyle, Robert Rajkumar, Vincent Landgren, Ola TI Polyclonal hypergammaglobulinemia in a randomized sample of Ghanaian adult males SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Buadi, Francis; Katzmann, Jerry A.; Dispenzieri, Angela; Kyle, Robert; Rajkumar, Vincent] Mayo Clin, Coll Med, Div Hematol, Rochester, MN USA. [Pfeiffer, Ruth M.; Hsing, Ann W.; Landgren, Ola] Natl Canc Inst, NIH, Bethesda, MD USA. [Yeboah, Edward D.; Biritwum, Richard B.] Univ Ghana, Sch Med, Accra, Ghana. RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 960 BP 292A EP 293A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801229 ER PT J AU Kovalchuk, AL Mushinski, E Burkholder, B Qi, CF Li, Z Shin, DM Morse, H Potter, M AF Kovalchuk, Alexander L. Mushinski, Elizabeth Burkholder, Brad Qi, Chen-Feng Li, Zhaoyang Shin, Dong-Mi Morse, Herbert Potter, Michael TI A novel mechanism of Ig and myc translocations in AID-deficient mice SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Kovalchuk, Alexander L.; Qi, Chen-Feng; Li, Zhaoyang; Shin, Dong-Mi; Morse, Herbert] NIAID, Immunopathol Lab, Rockville, MD USA. [Mushinski, Elizabeth; Burkholder, Brad; Potter, Michael] Natl Canc Inst, Cell Biol & Genet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 990 BP 300A EP 301A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801259 ER PT J AU Yokoyama, H Berg, M Lundqvist, A Mccoy, JP Srivastava, S Smith, A Childs, R AF Yokoyama, Hisayuki Berg, Maria Lundqvist, Andreas McCoy, J. Philip Srivastava, Shivani Smith, Aleah Childs, Richard TI Cyclosporine a (CSA) significantly reduces the cytotoxic effects of in vitro expanded NK cells: Implications for adoptive NK cell therapy in the setting of allogeneic hematopoietic stem cell transplantation (HCT) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Yokoyama, Hisayuki; Berg, Maria; Lundqvist, Andreas; Srivastava, Shivani; Smith, Aleah; Childs, Richard] NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [McCoy, J. Philip] NIH, NHLBI, Flow Cytometry Core Facil, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 4899 BP 300B EP 300B PG 1 WC Hematology SC Hematology GA 233OV UT WOS:000251101102191 ER PT J AU Ong, ASM Keyvanfar, K Hensel, N Eniafe, R Savani, BN Berg, M Lundqvist, A Sloand, EM Goldman, JM Childs, RW Barrett, AJ AF Ong, Agnes S. M. Keyvanfar, Keyvan Hensel, Nancy Eniafe, Rhoda Savani, Bipin N. Berg, Maria Lundqvist, Andreas Sloand, Elaine M. Goldman, John M. Childs, Richard W. Barrett, A. John TI Primitive quiescent CD34+cells in chronic myeloid luekemia are targeted by in vitro expanded allogeneic natural killer cells, which are functionally enhanced by bortezomib treatment SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Ong, Agnes S. M.; Keyvanfar, Keyvan; Hensel, Nancy; Eniafe, Rhoda; Savani, Bipin N.; Berg, Maria; Lundqvist, Andreas; Sloand, Elaine M.; Goldman, John M.; Childs, Richard W.; Barrett, A. John] NIH, NHLBI, Hematol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1008 BP 305A EP 306A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801277 ER PT J AU Imanguli, M Hakim, F Swaim, W Guadagnini, JP League, S Gress, R Pavletic, S AF Imanguli, Matin Hakim, Frances Swaim, William Guadagnini, Jean-Pierre League, Stacy Gress, Ronald Pavletic, Steven TI The balance of effector and regulatory cell populations in oral chronic GVHD: Potential role of IL-15 SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Imanguli, Matin; Hakim, Frances; League, Stacy; Gress, Ronald; Pavletic, Steven] NCI, NIH, Expt Transplant & Immunol Branch, Bethesda, MD USA. [Swaim, William] NIH, NIDCR, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. [Guadagnini, Jean-Pierre] NIH, NIDCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1059 BP 321A EP 321A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801328 ER PT J AU Dean, RM Fry, T Mackall, C Steinberg, SM Hakim, FT Fowler, DH Odom, J Foley, J Gress, RE Bishop, MR AF Dean, Robert M. Fry, Terry Mackall, Crystal Steinberg, Seth M. Hakim, Frances T. Fowler, Daniel H. Odom, Jeanne Foley, Jason Gress, Ronald E. Bishop, Michael R. TI Elevated serum interleukin-7 levels precede the development of acute graft-versus-host disease SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Dean, Robert M.; Hakim, Frances T.; Fowler, Daniel H.; Odom, Jeanne; Foley, Jason; Gress, Ronald E.; Bishop, Michael R.] NIH, Natl Canc Inst, Expt Transplant & Immunol Branch, CCR, Bethesda, MD 20892 USA. [Dean, Robert M.] Cleveland Clin Fdn, Taussig Canc Ctr, Cleveland, OH 44195 USA. [Fry, Terry; Mackall, Crystal] NIH, Natl Canc Inst, Pediat Oncol Branch, CCR, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NIH, Natl Canc Inst, Biostat & Data Management Branch, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1064 BP 322A EP 322A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801333 ER PT J AU Davies, SM Wang, D Wang, T Arora, A Ringden, O Anasetti, C Pavletic, S Casper, J MacMillan, ML Sanders, J Wall, D Kernan, NA AF Davies, Stella M. Wang, D. Wang, T. Arora, A. Ringden, O. Anasetti, C. Pavletic, S. Casper, J. MacMillan, M. L. Sanders, J. Wall, D. Kernan, N. A. TI Recent decrease in acute GVHD and increased relapse in children with leukemia receiving unrelated donor bone marrow transplants SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Davies, Stella M.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Wang, D.; Arora, A.] CIBMTR, Minneapolis, MN USA. [Wang, T.] CIBMTR, Milwaukee, WI USA. [Wang, T.] Karolinska Univ Hosp, Huddinge, Sweden. [Ringden, O.] H Lee Moffitt Canc Ctr & Res Inst, Res Inst, Tampa, FL USA. [Casper, J.] Natl Inst Hlth, Bethesda, MD USA. [Casper, J.] Med Coll Wisconsin, Milwaukee, WI USA. [MacMillan, M. L.] Univ Minnesota, Minneapolis, MN 55455 USA. [Sanders, J.] Fred Hutchinson Canc Res Inst, Seattle, WA USA. [Wall, D.] Texas Transplant Inst, San Antonio, TX USA. [Kernan, N. A.] Mem Sloan Kettering Canc Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1081 BP 327A EP 328A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801350 ER PT J AU Lozier, JN Weeks, B Tayebi, N AF Lozier, Jay Nelson Weeks, Brian Tayebi, Nahid TI Localization of non-factor VIII sequence involved in the factor VIII gene inversion in hemophilia A dogs. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Lozier, Jay Nelson; Weeks, Brian] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD USA. [Tayebi, Nahid] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 BP 347A EP 348A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801415 ER PT J AU Badros, A Philip, S Niesvizky, R Goloubeva, O Harris, C Zweibel, J Wright, J Burger, A Grant, S Baer, MK Egorin, MJ AF Badros, Ashraf Philip, S. Niesvizky, R. Goloubeva, O. Harris, C. Zweibel, J. Wright, J. Burger, A. Grant, S. Baer, M. K. Egorin, M. J. TI Phase I trial of suberoylanilide hydroxamic acid (SAHA) plus bortezomib (Bort) in relapsed multiple myeloma (MM) patients (pts). SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Badros, Ashraf; Philip, S.; Goloubeva, O.; Harris, C.; Burger, A.; Baer, M. K.] Univ Maryland, College Pk, MD 20742 USA. [Niesvizky, R.] Cornell Univ, New York, NY USA. [Zweibel, J.; Wright, J.] NCI, CTEP, Bethesda, MD USA. [Grant, S.] Virginia Commonwealth Univ Med Coll Virginia, Richmond, VA USA. [Egorin, M. J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1168 BP 354A EP 354A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801437 ER PT J AU Dispenzieri, A Myers, RM Tong, C Greiner, SM Harvey, ME Griesmann, G Reid, J Federspiel, M Ames, MM Dingli, D Lacy, MQ Gertz, MA Schweikwart, K Welch, A Peng, KW Russell, SJ AF Dispenzieri, Angela Myers, Rae M. Tong, Caili Greiner, Suzanne M. Harvey, Mary E. Griesmann, Guy Reid, Joel Federspiel, Mark Ames, Matthew M. Dingli, David Lacy, Martha Q. Gertz, Morie A. Schweikwart, Karen Welch, Anthony Peng, Kah-Whye Russell, Stephen J. TI Pre-clinical data and preliminary patient results of intravenous MV-NIS to treat relapsed, refractory multiple myeloma SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Myers, Rae M.; Tong, Caili; Greiner, Suzanne M.; Harvey, Mary E.; Griesmann, Guy; Federspiel, Mark; Peng, Kah-Whye; Russell, Stephen J.] Mayo Clin, Program Mol Med, Rochester, MN USA. [Dispenzieri, Angela; Dingli, David; Lacy, Martha Q.; Gertz, Morie A.] Mayo Clin, Div Hematol, Rochester, MN USA. [Reid, Joel; Ames, Matthew M.] Mayo Clin, Rochester, MN USA. [Schweikwart, Karen] NCI, Dev Therapeut Program, Toxicol & Pharmacol Branch, Bethesda, MD 20892 USA. [Welch, Anthony] NCI, Div Canc Treatment & Diagnosis, Biol Resources Branch, Frederick, MD 21701 USA. RI Dingli, David/B-6355-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1181 BP 358A EP 358A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801450 ER PT J AU Hayakawa, J Hsieh, M Phang, OJ Uchida, N Tisdale, JF AF Hayakawa, Jun Hsieh, Matt Phang, O. J. Uchida, Naoya Tisdale, John F. TI Low dose busulfan produces efficient human cell engraftment in immunodeficient mice SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Hayakawa, Jun; Hsieh, Matt; Phang, O. J.; Uchida, Naoya; Tisdale, John F.] NIH, NIDDK, MCHB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1194 BP 362A EP 362A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801463 ER PT J AU Pilon, AM Beaupre, J Bieker, JJ Gallagher, PG Bodine, DM AF Pilon, Andre M. Beaupre, Jacqueline Bieker, James J. Gallagher, Patrick G. Bodine, David M. TI Multiple defects of both primitive and definitive erythrocytes in EKLF-deficient mice. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Pilon, Andre M.; Beaupre, Jacqueline; Bodine, David M.] NHGRI, Hematopoiesis Sect, GMBB, Bethesda, MD 20892 USA. [Bieker, James J.] Mt Sinai Sch Med, New York, NY USA. [Gallagher, Patrick G.] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1234 BP 373A EP 373A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801503 ER PT J AU Cai, Y Xu, Z Nagarajan, L Brandt, SJ AF Cai, Ying Xu, Zhixiong Nagarajan, Lalitha Brandt, Stephen J. TI Single-stranded DNA-Binding proteins (SSBPs) regulate the abundance of the LIM-homeodomain protein LHX2 and augment its transcriptional activity. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Cai, Ying; Brandt, Stephen J.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [Xu, Zhixiong] NIDDK, NIH, Bethesda, MD USA. [Nagarajan, Lalitha] MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1239 BP 374A EP 375A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801508 ER PT J AU Rogers, HM Prchal, JT Weksler, BB Yu, X Noguchi, CT AF Rogers, Heather M. Prchal, Josef T. Weksler, Babette B. Yu, Xiaobing Noguchi, Constance Tom TI Excessive isolated erythrocytosis linked to induction of SCL/Tal1 and erythropoietin receptor expression. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Rogers, Heather M.; Noguchi, Constance Tom] NIDDK, Natl Inst Hlth, Mol Med Branch, Bethesda, MD USA. [Prchal, Josef T.] Univ Utah, Sch Med, Div Hematol, Salt Lake City, UT 84112 USA. [Weksler, Babette B.] Weill Cornell Med Coll, Div Hematol Oncol, New York, NY USA. [Yu, Xiaobing] Johns Hopkins Univ, Inst Cell Engn, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1244 BP 375A EP 376A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801512 ER PT J AU Dale, JK Price, S Tretler, J Aldridge, P Montague, S Davis, J Gill, F Hartman, KR Stork, LC Gnarra, DJ Krishnamurti, L Puck, J Fleisher, T Rao, VK AF Dale, Janet K. Price, Susan Tretler, Jean Aldridge, Patricia Montague, Stephanie Davis, Joie Gill, Fred Hartman, Kip R. Stork, Linda C. Gnarra, David J. Krishnamurti, Lakshmianan Puck, Jennifer Fleisher, Thomas Rao, V. Koneti TI Use of rituximab for refractory immune cytopenias associated with autoimmune lymphoproliferative syndrome (ALPS) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Dale, Janet K.; Price, Susan; Tretler, Jean; Aldridge, Patricia; Montague, Stephanie; Davis, Joie; Gill, Fred; Fleisher, Thomas; Rao, V. Koneti] NIAID, Natl Inst Hlth, NHGRI, Bethesda, MD USA. [Hartman, Kip R.] Walter Reed Army Med Ctr, Washington, DC USA. [Stork, Linda C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Gnarra, David J.] Childrens Hosp, Omaha, NE USA. [Krishnamurti, Lakshmianan] Childrens Hosp Pittsburgh, Div Hematol Oncol, BMT, Pittsburgh, PA USA. [Puck, Jennifer] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1319 BP 397A EP 397A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801587 ER PT J AU Calado, RT Graf, SA Young, NS AF Calado, Rodrigo T. Graf, Solomon A. Young, Neal S. TI Telomeric recombination in lymphocytes implicates ALT, an alternative mechanism for telomere length maintenance, in normal human hematopoietic cells SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Calado, Rodrigo T.; Graf, Solomon A.; Young, Neal S.] Natl Inst Hlth, NHLBI, Hematol Branch, Bethesda, MD USA. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1332 BP 401A EP 402A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801600 ER PT J AU Guimond, M Veenstra, RG Grindler, DJ Cui, Y Na, R Hennighausen, L Zhang, H Merchant, MS Mackall, C AF Guimond, Martin Veenstra, Rachelle G. Grindler, David J. Cui, Yongzi Na, Risu Hennighausen, Lothar Zhang, Hua Merchant, Melinda S. Mackall, Crystal TI Interleukin-7 produced by antigen presenting cells regulates the homeostatic peripheral expansion of naive CD4 T cells SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Guimond, Martin; Veenstra, Rachelle G.; Grindler, David J.; Cui, Yongzi; Zhang, Hua; Merchant, Melinda S.; Mackall, Crystal] NCI, NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Na, Risu; Hennighausen, Lothar] NCI, NIDDK, Biol Mammary Gland Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1333 BP 402A EP 402A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801601 ER PT J AU Wang, HS Feng, JX Lee, CH Morse, H AF Wang, Hongsheng Feng, Jianxun Lee, Chang Hoon Morse, Herbert TI B cell lineage-specific deletion of Icsbp/IRF8 reveals roles for IRF8 in the regulation of marginal zone and follicular B cell development SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Wang, Hongsheng; Feng, Jianxun; Lee, Chang Hoon; Morse, Herbert] NIH, NIAID, Immunopathol Lab, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1334 BP 402A EP 402A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801602 ER PT J AU Li, ZY Xuei, LQ Shin, DM Qi, CF Zhang, QG Xu, W Morris, SW Morse, H Wang, HS AF Li, Zhaoyang Xuei, Liquan Shin, Dong-Mi Qi, Chen-Feng Zhang, Quangeng Xu, Wu Morris, Stephan W. Morse, Herbert Wang, Hongsheng TI Constitutive activation of the canonical NF-kappa B signaling pathway and expanded populations of splenic marginal zone B cells characterize Em-BCL10 Transgenic mice SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Li, Zhaoyang; Shin, Dong-Mi; Qi, Chen-Feng; Morse, Herbert; Wang, Hongsheng] NIH, NIAID, Lab Immunopathol, Rockville, MD USA. [Xuei, Liquan; Zhang, Quangeng; Xu, Wu; Morris, Stephan W.] St Jude Childrens Hosp, Dept Pathol & Oncol, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1341 BP 404A EP 404A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801609 ER PT J AU Li, Z Xue, L Shin, DM Qi, CF Zhang, Q Xu, W Morris, SW Morse, H Wang, H AF Li, Zhaoyang Xue, Liquan Shin, Dong-Mi Qi, Chen-Feng Zhang, Quangeng Xu, Wu Morris, Stephan W. Morse, Herbert Wang, Hongsheng TI Critical role for CD81 in B cell activation SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Li, Zhaoyang; Shin, Dong-Mi; Qi, Chen-Feng; Morse, Herbert; Wang, Hongsheng] NIAID, Natl Inst Hlth, Immunopathol Lab, Rockville, MD USA. [Xue, Liquan; Zhang, Quangeng; Xu, Wu; Morris, Stephan W.] St Jude Childrens Hosp, Dept Pathol & Oncol, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1342 BP 404A EP 404A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801610 ER PT J AU Melenhorst, JJ Scheinberg, P Gostick, E Chattopadhyay, PK Lissina, A Cole, DK Roederer, M Bornstein, E Hensel, NF Douek, DC Sewell, AK Barrett, AJ Price, DA AF Melenhorst, J. Joseph Scheinberg, Phillip Gostick, Emma Chattopadhyay, Pratip K. Lissina, Anna Cole, David K. Roederer, Mario Bornstein, Ethan Hensel, Nancy F. Douek, Daniel C. Sewell, Andrew K. Barrett, A. John Price, David A. TI Peptide-major histocompatibility complex class I tetramers with enhanced coreceptor binding properties enable visualization of low avidity leukemia-associated antigen-specific CD8(+) T cells SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Melenhorst, J. Joseph; Scheinberg, Phillip; Hensel, Nancy F.; Barrett, A. John] Natl Inst Hlth, NHLBI, Bethesda, MD USA. [Scheinberg, Phillip; Bornstein, Ethan; Douek, Daniel C.; Price, David A.] Natl Inst Hlth, NIAID, Vaccine Res Ctr, Human Immunol Sect, Bethesda, MD USA. [Gostick, Emma; Price, David A.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX1 2JD, England. [Chattopadhyay, Pratip K.; Roederer, Mario] Natl Inst Hlth, NIAID, Vaccine Res Ctr, Immunotechnol Sect, Bethesda, MD USA. [Lissina, Anna; Cole, David K.; Sewell, Andrew K.] Cardiff Univ, Cardiff, Wales. RI Chattopadhyay, Pratip/B-9227-2008; Cole, David/C-8387-2012; Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1343 BP 404A EP 404A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801611 ER PT J AU Weichsel, R Dix, C Wooldrige, L Clement, M Fenton-May, A Zezula, J Greiner, E Gostick, E Price, DA Einsele, H Seggewis, R AF Weichsel, Ralf Dix, Carolin Wooldrige, Linda Clement, Matthew Fenton-May, Angharad Zezula, Josef Greiner, Elisabeth Gostick, Emma Price, David A. Einsele, Hermann Seggewis, Ruth TI Profound shut-down of antigen specific T-Cell effector functions by dasatinib SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Weichsel, Ralf; Dix, Carolin; Einsele, Hermann; Seggewis, Ruth] Univ Wurzburg, Med Klin & Poliklin 2, Recovery Lab, D-97070 Wurzburg, Germany. [Wooldrige, Linda; Clement, Matthew; Fenton-May, Angharad] Cardiff Univ, Cardiff, Wales. [Zezula, Josef; Greiner, Elisabeth] NIDDK, NIH, DHHS, Med Chem Lab, Bethesda, MD USA. [Gostick, Emma; Price, David A.] Univ Oxford, Weatherall Inst Mol Med, Oxford OX1 2JD, England. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1348 BP 405A EP 406A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801616 ER PT J AU Wilson, WH Tulpule, A Levine, AM Dunleavy, K Krivoshik, AP Hagey, AE Shovlin, M Gloria, MA Greco, R Xiong, H Chiu, YL Elmore, SW O'Connor, OA AF Wilson, Wyndham H. Tulpule, Anil Levine, Alexandra M. Dunleavy, Kieron Krivoshik, Andrew P. Hagey, Anne E. Shovlin, Margaret Gloria, Melanie A. Greco, Renee Xiong, Hao Chiu, Yi-Lin Elmore, Steven W. O'Connor, Owen A. TI A phase 1/2a study evaluating the safety, pharmacokinetics, and efficacy of ABT-263 in subjects with refractory or relapsed lymphoid malignancies SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Wilson, Wyndham H.; Dunleavy, Kieron; Shovlin, Margaret] Natl Canc Inst, Ctr Canc Res, Metab Branch, Bethesda, MD USA. [Tulpule, Anil] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA USA. [Levine, Alexandra M.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Krivoshik, Andrew P.; Hagey, Anne E.; Greco, Renee; Elmore, Steven W.] Abbott Labs, Abbott Pk, IL 60064 USA. [O'Connor, Owen A.] Columbia Univ, Presbyterian Hosp, Herbert Irving Comprehens Canc Ctr, New York, NY USA. NR 0 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1371 BP 412A EP 412A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801639 ER PT J AU Tabe, Y Szbasigari, D Rudelius, M Pittaluga, S Raffel, M AF Tabe, Yoko Szbasigari, Denise Rudelius, Martina Pittaluga, Stefania Raffel, Mark TI The MDM2 antagonist nutlin-3 is lethal to mantle cell lymphoma with wild type p53 SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Tabe, Yoko; Szbasigari, Denise; Rudelius, Martina; Pittaluga, Stefania; Raffel, Mark] Natl Canc Inst, Pathol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1382 BP 415A EP 415A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801650 ER PT J AU Dowdell, KC Pesnicak, L Bi, L Hoffmann, V Rao, VK Straus, SE AF Dowdell, Kennichi C. Pesnicak, Lesley Bi, Lilia Hoffmann, Victoria Rao, V. Koneti Straus, Stephen E. TI Hydroxychloroquine diminishes lymphoproliferation in the fas deficient MRL/lpr-/- murine model of autoimmune lymphoproliferative syndrome (ALPS) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Dowdell, Kennichi C.; Pesnicak, Lesley; Rao, V. Koneti; Straus, Stephen E.] NIH, NIAID, LCID, Bethesda, MD USA. [Bi, Lilia] CBER, FDA, Bethesda, MD USA. [Hoffmann, Victoria] NIH, DVM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1385 BP 416A EP 416A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801653 ER PT J AU Varticovski, L Wright, MH Caldas-Lopes, E Chiosis, G Robles, AI AF Varticovski, Lyuba Wright, Mollie H. Caldas-Lopes, Eloisi Chiosis, Gabriela Robles, Ana I. TI Synergy of the purine-scaffold HSP90 inhibitor, PU-H71, with doxorubicin in non-Hodgkin's lymphoma cell lines SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Varticovski, Lyuba; Wright, Mollie H.; Robles, Ana I.] NCI, Canc Res Ctr, Bethesda, MD USA. [Caldas-Lopes, Eloisi; Chiosis, Gabriela] Sloan Kettering Inst Canc Res, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1399 BP 420A EP 420A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801667 ER PT J AU Harvey, RC Davidson, GS Wang, X Dobbin, KK Bedrick, EJ Wilson, CS Atlas, SR Kang, H Chen, IM Hunger, SP Devidas, M Carroll, WL Bowman, P Camitta, B Reaman, G Willman, CL AF Harvey, Richard C. Davidson, George S. Wang, Xuefei Dobbin, Kevin K. Bedrick, Edward J. Wilson, Carla S. Atlas, Susan R. Kang, Huining Chen, I-Ming Hunger, Stephen P. Devidas, Meenakshi Carroll, William L. Bowman, Paul Camitta, Bruce Reaman, Gregory Willman, Cheryl L. TI Expression profiling identifies novel genetic subgroups with distinct clinical features and outcome in high-risk pediatric precursor B acute lymphoblastic leukemia (B-ALL). A children's oncology group study SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Harvey, Richard C.; Wang, Xuefei; Bedrick, Edward J.; Wilson, Carla S.; Atlas, Susan R.; Kang, Huining; Chen, I-Ming; Willman, Cheryl L.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Harvey, Richard C.; Chen, I-Ming; Hunger, Stephen P.; Devidas, Meenakshi; Carroll, William L.; Bowman, Paul; Camitta, Bruce; Reaman, Gregory] Childrens Oncol Grp, Arcadia, CA USA. [Davidson, George S.] Sandia Natl Labs, Albuquerque, NM USA. [Dobbin, Kevin K.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 BP 428A EP 429A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100801698 ER PT J AU Raponi, M Lancet, JE Fan, H Dossey, L Lee, G Gojo, I Feldman, EJ Gotlib, J Morris, LE Greenberg, PL Wright, JJ Harousseau, JL Lowenberg, B Stone, RM De Porre, P Wang, Y Karp, JE AF Raponi, Mitch Lancet, Jeffrey E. Fan, Hongtao Dossey, Lesley Lee, Grace Gojo, Ivana Feldman, Eric J. Gotlib, Jason Morris, Lawrence E. Greenberg, Peter L. Wright, John J. Harousseau, Jean-Luc Lowenberg, Bob Stone, Richard M. De Porre, Peter Wang, Yixin Karp, Judith E. TI A two-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Raponi, Mitch; Dossey, Lesley; Wang, Yixin] Johnson & Johnson Co, Veriex LLC, San Diego, CA USA. [Lancet, Jeffrey E.] Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Fan, Hongtao; Lee, Grace] Johnson & Johnson Co, Pharma Biomaker Support Grp, San Diego, CA USA. [Gojo, Ivana] Univ Maryland, Greenbaum Canc Ctr, College Pk, MD 20742 USA. [Feldman, Eric J.] Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. [Gotlib, Jason; Greenberg, Peter L.] Stanford Univ, Stanford Canc Ctr, Stanford, CA USA. [Morris, Lawrence E.] Blood & Bone Marrow Transplant Grp Georgia, Atlanta, GA USA. [Wright, John J.] Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA. [Harousseau, Jean-Luc] CHRU Hotel Dieu, Serv Hematol Clin, Nantes, France. [Harousseau, Jean-Luc] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. [Lowenberg, Bob] Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA USA. [Stone, Richard M.] Johnson & Johnson Pharmaceut Res Inst, Beerse, Belgium. [De Porre, Peter; Karp, Judith E.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1445 BP 433A EP 433A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801713 ER PT J AU Cerhan, JR Maurer, MJ Hartge, P Chanock, SJ Habermann, TM Cozen, W Davis, S Lynch, CF Severson, RK Rothman, N Morton, LM Wang, SS AF Cerhan, James R. Maurer, Matthew J. Hartge, Patricia Chanock, Stephen J. Habermann, Thomas M. Cozen, Wendy Davis, Scott Lynch, Charles F. Severson, Richard K. Rothman, Nathaniel Morton, Lindsay M. Wang, Sophia S. TI Polymorphisms in one-carbon metabolism genes and overall survival in diffuse large B-cell lymphoma (DLBCL) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Cerhan, James R.; Maurer, Matthew J.; Habermann, Thomas M.] Mayo Clin, Coll Med, Rochester, MN USA. [Hartge, Patricia; Chanock, Stephen J.; Rothman, Nathaniel; Morton, Lindsay M.; Wang, Sophia S.] Natl Canc Inst, Rockville, MD USA. [Davis, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Cozen, Wendy] Univ So Calif, Los Angeles, CA 90089 USA. [Lynch, Charles F.] Univ Iowa, Iowa City, IA 52242 USA. [Severson, Richard K.] Wayne State Univ, Detroit, MI 48202 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1568 BP 469A EP 469A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802090 ER PT J AU Habermann, TM Maurer, MJ Wang, SS Morton, LM Lynch, CF Hartge, P Cozen, W Severson, RK Scott, D Watson, DA Chanock, SJ Rothnnan, N Cerhan, JR AF Habermann, Thomas M. Maurer, Matthew J. Wang, Sophia S. Morton, Lindsay M. Lynch, Charles F. Hartge, Patricia Cozen, Wendy Severson, Richard K. Scott, Davis Watson, David A. Chanock, Stephen J. Rothnnan, Nathamal Cerhan, James R. TI Host genetic variation in the cell cycle and NF-kappa B pathways and overall survival in mantle cell lymphoma SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Habermann, Thomas M.; Maurer, Matthew J.; Watson, David A.; Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN USA. [Wang, Sophia S.; Morton, Lindsay M.; Hartge, Patricia; Chanock, Stephen J.; Rothnnan, Nathamal] Natl Canc Inst, Bethesda, MD USA. [Cozen, Wendy] Univ So Calif, Los Angeles, CA USA. [Scott, Davis] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Severson, Richard K.] Karmonas Canc Inst, Detroit, MI USA. [Lynch, Charles F.] Univ Iowa, Iowa City, IA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1582 BP 472A EP 473A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100802104 ER PT J AU Klier, M Anastasov, N Angermeier, D Raffeld, M Fend, F Quintanilla-Martinez, L AF Klier, Margit Anastasov, Natasa Angermeier, Daniela Raffeld, Mark Fend, Falko Quintanilla-Martinez, Leticia TI Functional analysis of cyclin D1 in mantle cell lymphoma (MCL) by specific lentiviral shRNA mediated knockdown SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Klier, Margit; Anastasov, Natasa; Angermeier, Daniela; Quintanilla-Martinez, Leticia] Natl Res Ctr Hlth & Environm, Neuherberg, Germany. [Raffeld, Mark] Natl Inst Hlth, Natl Canc Ctr, Pathol Lab, Hematopathol Sect, Bethesda, MD USA. [Fend, Falko] Tech Univ, Munich, Germany. RI Anastasov, Natasa/M-9848-2014 OI Anastasov, Natasa/0000-0002-4088-1119 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1584 BP 473A EP 473A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802106 ER PT J AU Rudelius, M Sebasigari, D Tabe, Y Davies-Hill, T Fend, F Leticia, QM Elaine, JS Stefania, P Mark, R AF Rudelius, Martina Sebasigari, Denise Tabe, Yoko Davies-Hill, Theresa Fend, Falko Leticia, Quintanilla-Martinez Elaine, Jaffe S. Stefania, Pittaluga Mark, Raffeld TI The BCR-associated tyrosine kinase SYK is linked to the activation of AKT in mantle cell lymphoma SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Rudelius, Martina; Sebasigari, Denise; Tabe, Yoko; Davies-Hill, Theresa; Elaine, Jaffe S.; Stefania, Pittaluga; Mark, Raffeld] Natl Canc Inst, Pathol Lab, Bethesda, MD USA. [Rudelius, Martina; Fend, Falko] Tech Univ Munich, Inst Pathol, Munich, Germany. [Leticia, Quintanilla-Martinez] GSF, Natl Res Ctr Hlth & Environm, Neuherberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1586 BP 473A EP 474A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100802108 ER PT J AU Li, Q Haigis, K McDaniel, A Huang, B Miller, M Shieh, A Kogan, S Wolff, L Jacks, T Shannon, K AF Li, Qing Haigis, Kevin McDaniel, Andrew Huang, Benjamin Miller, Michelle Shieh, Angell Kogan, Scott Wolff, Lynda Jacks, Tyler Shannon, Kevin TI Expressing N-Ras(G12D) from the endogenous promoter induces myeloproliferative disease (MPD) and cooperates with retroviral insertional mutagenesis (RIM) to generate acute myeloid leukemia (AML) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Li, Qing; McDaniel, Andrew; Huang, Benjamin; Miller, Michelle; Shieh, Angell; Kogan, Scott; Shannon, Kevin] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Haigis, Kevin; Jacks, Tyler] MIT, Cambridge, MA 02139 USA. [Wolff, Lynda] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1616 BP 482A EP 483A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100802138 ER PT J AU Slape, C Liu, LY Aplan, PD AF Slape, Christopher Liu, Leah Y. Aplan, Peter D. TI Leukemic transformation in mice expressing a NUP98-HOXD13 transgene is accompanied by spontaneous mutations in receptor tyrosine kinase pathway genes SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Slape, Christopher; Liu, Leah Y.; Aplan, Peter D.] Ctr Canc Res, Natl Canc Inst, NIH, Genet Branch, Bethesda, MD USA. RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016 OI Slape, Christopher/0000-0002-8407-3092; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1614 BP 482A EP 482A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802136 ER PT J AU Bashey, A Medina, B Corringham, S Pasek, M Carrier, E Vrooman, L Streicher, H Lowy, I Solomon, SW Morris, LE Holland, K Mason, JR Soiffer, RJ Ball, ED AF Bashey, Asad Medina, Bridget Corringham, Sue Pasek, Mildred Carrier, Ewa Vrooman, Linda Streicher, Howard Lowy, Israel Solomon, Scott W. Morris, Lawrence E. Holland, Kent Mason, James R. Soiffer, Robert J. Ball, Edward D. TI Clinical trial of therapeutic blockade of CTLA4 with ipilimumab in patients with relapse of malignancy following allogeneic hematopoietic transplantation SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Bashey, Asad; Medina, Bridget; Corringham, Sue; Carrier, Ewa; Ball, Edward D.] Univ Calif San Diego, Moores Canc Ctr, Blood & Marrow Transplant Program, La Jolla, CA 92093 USA. [Pasek, Mildred; Vrooman, Linda; Soiffer, Robert J.] Dana Farber Canc Inst, Boston, MA USA. [Streicher, Howard] NCI, Pharmaceut Management Branch, Bethesda, MD 20892 USA. [Lowy, Israel] Medarex Inc, Bloomsburg, NJ USA. [Mason, James R.] Scripps Clin, La Jolla, CA USA. [Solomon, Scott W.; Morris, Lawrence E.; Holland, Kent] Georgia Northside Hosp, Blood Marrow Transplant Grp, Atlanta, GA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1646 BP 491A EP 491A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802168 ER PT J AU Pusic, I Dickinson, J Steinberg, S Odom, J Atlam, N Mitchell, S Avila, D Krumlauf, M Baird, K Pavletic, S AF Pusic, Iskra Dickinson, John Steinberg, Seth Odom, Jeanne Atlam, Niveen Mitchell, Sandra Avila, Daniele Krumlauf, Michael Baird, Kristin Pavletic, Steven TI Burden of illness in chronic Graft vs. Host disease - A prospective cohort study SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Pusic, Iskra; Dickinson, John; Steinberg, Seth; Odom, Jeanne; Atlam, Niveen; Mitchell, Sandra; Avila, Daniele; Krumlauf, Michael; Baird, Kristin; Pavletic, Steven] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1667 BP 497A EP 497A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802189 ER PT J AU Giri, N Butman, JA Keil, MF Stratakis, CA Alter, BP AF Giri, Neelam Butman, John A. Keil, Meg F. Stratakis, Constantine A. Alter, Blanche P. TI Central nervous system abnormalities in dyskeratosis congenita and Fanconi anemia: Correlation with clinical phenotype and aplastic anemia SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Giri, Neelam; Alter, Blanche P.] NCI, DCEG, Clin Genet Branch, Bethesda, MD 20892 USA. [Keil, Meg F.; Stratakis, Constantine A.] NICHHD, NIH, Bethesda, MD 20892 USA. RI Butman, John/A-2694-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1682 BP 501A EP 502A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100802204 ER PT J AU Chen, JC Young, NS AF Chen, Jichun Young, Neal S. TI Cell therapy in a mouse model of immune-mediated bone marrow failure SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Chen, Jichun; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1689 BP 503A EP 504A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100802211 ER PT J AU Scheinberg, P Wu, CO Nunez, O Yong, NS AF Scheinberg, Phillip Wu, Colin O. Nunez, Olga Yong, Neal S. TI Predicting response and survival for severe aplastic anemia patients treated with immunosuppiession SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Scheinberg, Phillip; Nunez, Olga; Yong, Neal S.] NHLBI, Hematol Branch, Bethesda, MD USA. [Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1691 BP 504A EP 504A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802213 ER PT J AU Scheinberg, P Wu, CO Nunez, O Young, N AF Scheinberg, Phillip Wu, Colin O. Nunez, Olga Young, Neal TI Long term outcome of pediatric patients with severe aplastic anemia treated with anti-thymocyte globulin and cyclosporine SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Scheinberg, Phillip; Nunez, Olga; Young, Neal] NHLBI, Hematol Branch, Bethesda, MD USA. [Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1694 BP 505A EP 505A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802216 ER PT J AU Scheinberg, P Wu, CO Nunez, O Young, NS AF Scheinberg, Phillip Wu, Colin O. Nunez, Olga Young, Neal S. TI Marked improvement in short- and long-term survival in severe aplastic anemia patients treated with immunosuppression in the past 18 years SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Scheinberg, Phillip; Nunez, Olga; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD USA. [Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1698 BP 506A EP 506A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802220 ER PT J AU Sloand, E Scheinberg, P Fenlon, E Blancato, J Pfannes, L Sloand, EM Young, NS AF Sloand, Elaine Scheinberg, Phillip Fenlon, Edward Blancato, Jan Pfannes, Loretta Sloand, Elaine. M. Young, Neal S. TI Monosomy 7 detected by FISH at disease presentation is a marker for non-response to immunosuppression SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Sloand, Elaine; Scheinberg, Phillip; Pfannes, Loretta; Sloand, Elaine. M.; Young, Neal S.] NHLBI, Div Intramural Res, Hematol Branch, Bethesda, MD USA. [Fenlon, Edward; Blancato, Jan] Georgetown Univ, Washington, DC 20057 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1697 BP 506A EP 506A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802219 ER PT J AU Steiner, LA Lin, JY Owens, AN Sangerman, JI Bodine, DM Gallagher, PG AF Steiner, Laurie A. Lin, Jolinta Y. Owens, Ashley N. Sangerman, Jose I. Bodine, David M. Gallagher, Patrick G. TI Alternate promoters direct tissue-specific expression of erythrocyte ankyrin transcripts with novel NH2-Termini. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Steiner, Laurie A.; Sangerman, Jose I.; Gallagher, Patrick G.] Yale Univ, New Haven, CT USA. [Lin, Jolinta Y.; Owens, Ashley N.; Bodine, David M.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1710 BP 509A EP 510A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100802232 ER PT J AU Bhatia, H Hallock, J Sterner, L Miyazaki, T Dean, A Little, J AF Bhatia, Himdnshu Hallock, Jennifer Sterner, Lauren Miyazaki, Toru Dean, Ann Little, Jane TI Endogenous elevations of short chain fatty acids (SCFAs) can up-regulate embryonic globin gene expression SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Bhatia, Himdnshu; Little, Jane] Albert Einstein Coll Med, Bronx, NY USA. [Hallock, Jennifer; Sterner, Lauren; Dean, Ann] Natl Inst Hlth, NIDDK, Cellular & Dev Biol Lab, Bethesda, MD USA. [Miyazaki, Toru] Univ Texas, Grad Sch Biomed Sci, Ctr Immunol, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1770 BP 525A EP 525A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802292 ER PT J AU Bhupatiraju, AV Josleyn, NM Lee, YT Miller, JL AF Bhupatiraju, Ajoy V. Josleyn, Nicole M. Lee, Y. Terry Miller, Jeffery L. TI Mitosis is not required for coordinated changes in iron metabolism and high-level globin gene transcription in erythropoietin-responsive CD34+cells SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Bhupatiraju, Ajoy V.; Josleyn, Nicole M.; Lee, Y. Terry; Miller, Jeffery L.] Natl Inst Hlth, NIDDK, Mol Med Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1776 BP 527A EP 527A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802298 ER PT J AU Tanno, T Porayette, P Bhupatiraju, A Staker, P Lee, YT Fucharoen, S Paulson, RF Miller, JL AF Tanno, Toshihiko Porayette, Prashanth Bhupatiraju, Ajoy Staker, Pamela Lee, Y. Terry Fucharoen, Suthat Paulson, Robert F. Miller, Jeffery L. TI Twisted gastrulation (TWSG1) 1s expressed at elevated levels in thalassemia and regulates bone morphogenic protein signalinig SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Tanno, Toshihiko; Bhupatiraju, Ajoy; Staker, Pamela; Lee, Y. Terry; Miller, Jeffery L.] NIDDK, NIH, Bethesda, MD 20892 USA. [Porayette, Prashanth; Paulson, Robert F.] Penn State Univ, State Coll, Dept Vet Biomed Sci, University Pk, PA 16802 USA. [Fucharoen, Suthat] Mahidol Univ, Thalassemia Res Ctr, Int Sci & Technol Res & Dev, Bangkok 10700, Thailand. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1785 BP 529A EP 529A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802307 ER PT J AU Lundqvist, A Rao, S Smith, A Berg, M Su, S Yokohama, H Srivastava, S Childs, R AF Lundqvist, Andreas Rao, Sheila Smith, Aleah Berg, Maria Su, Su Yokohama, Hisayuki Srivastava, Shivani Childs, Richard TI Bortezomib enhances the antitumor activity of adoptively infused natural killer cells in vivo: A novel approach to override KIR-mediated inhibition of NK cell cytotoxicity SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Lundqvist, Andreas; Rao, Sheila; Smith, Aleah; Berg, Maria; Su, Su; Yokohama, Hisayuki; Srivastava, Shivani; Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1786 BP 530A EP 530A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802308 ER PT J AU Lundqvist, A Rao, S Berg, M Smith, A Su, S Yokoyama, H Srivastava, S Childs, R AF Lundqvist, Andreas Rao, Sheila Berg, Maria Smith, Aleah Su, Su Yokoyama, Hisayuki Srivastava, Shivani Childs, Richard TI The proteasome inhibitor bortezomib simultaneously enhances NK cell tumor cytotoxicity while paradoxically reducing antigen specific T-cell tumor cytotoxicity SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Lundqvist, Andreas; Rao, Sheila; Berg, Maria; Smith, Aleah; Su, Su; Yokoyama, Hisayuki; Srivastava, Shivani; Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1789 BP 530A EP 531A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100802311 ER PT J AU Capitini, CM Guimond, M Mackall, CL Fry, TJ AF Capitini, Christian M. Guimond, Martin Mackall, Crystal L. Fry, Terry J. TI GVHD abrogates T cell responses to dendritic cell vaccines but not vaccine-induced proliferation SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Capitini, Christian M.; Guimond, Martin; Mackall, Crystal L.; Fry, Terry J.] NIH, NCI, Pediat Oncol Branch, Bethesda, MD USA. [Fry, Terry J.] Childrens Natl Med Ctr, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1802 BP 534A EP 534A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802324 ER PT J AU Le, Q Melenhorst, JJ Hewitt, RE Hensel, N Barrett, AJ AF Le, Quart Melenhorst, J. Joseph Hewitt, Rachel E. Hensel, Nancy Barrett, A. John TI Identification of a shared CD4+ and CD8+ T cell epitope within human neutrophil elastase for peptide vaccination in HLA-A02 negative leukemia patients SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Le, Quart; Melenhorst, J. Joseph; Hewitt, Rachel E.; Hensel, Nancy; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1803 BP 534A EP 534A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802325 ER PT J AU Le, Q Melenhorst, JJ Hensel, N Eniafe, R Barrett, AJ AF Le, Quan Melenhorst, J. Joseph Hensel, Nancy Eniafe, Rhoda Barrett, A. John TI Human neutrophil elastase stimulating CD4+ and CD8+ T cells is a potential protein vaccine for leukemia patients with diverse HLA types SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Le, Quan; Melenhorst, J. Joseph; Hensel, Nancy; Eniafe, Rhoda; Barrett, A. John] NIH, NHLBI, Stem Cell Allotransplant Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1807 BP 535A EP 536A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100802329 ER PT J AU Kadia, TM Ferrajoli, A Ravandi, F Cortes, J Thomas, D Wierda, W Verstovsek, S Newsome, W Zwiebel, J Egorin, M Kantaijian, H Garcia-Manero, G AF Kadia, Tapan M. Ferrajoli, Alessandra Ravandi, Farhad Cortes, Jorge Thomas, Deborah Wierda, William Verstovsek, Srdan Newsome, Willie Zwiebel, James Egorin, Merrill Kantaijian, Hagop Garcia-Manero, Guillermo TI A phase I study of the combination of the histone deacetylase inhibitor vorinostat with idarubicin in advanced acute leukemia SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Kadia, Tapan M.; Ferrajoli, Alessandra; Ravandi, Farhad; Cortes, Jorge; Thomas, Deborah; Wierda, William; Verstovsek, Srdan; Kantaijian, Hagop; Garcia-Manero, Guillermo] Md Anderson Canc Ctr, Houston, TX USA. [Zwiebel, James] Natl Inst Hlth, Canc Therapy Evaluat Program, Bethesda, MD USA. [Egorin, Merrill] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1842 BP 545A EP 545A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802364 ER PT J AU Le, Q Savani, BN Shenoy, A Kozanas, E Barrett, AJ AF Le, Quan Savani, Bipin N. Shenoy, Aarthi Kozanas, Eleftheria Barrett, A. John TI Hepatitis B reverse seroconversion in long term survivors of allogeneic hematopoietic stem cell transplantation SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Le, Quan; Savani, Bipin N.; Shenoy, Aarthi; Kozanas, Eleftheria; Barrett, A. John] NIH, NHLBI, Stem Cell Allotransplantat Sect, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1978 BP 588A EP 589A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100802500 ER PT J AU Tolar, J Orchard, PJ Miller, JS MacMillan, ML Wagner, JE Alter, BP Baker, KS AF Tolar, Jakub Orchard, Paul J. Miller, Jeffrey S. MacMillan, Margaret L. Wagner, John E. Alter, Blanche P. Baker, K. S. TI Dyskeratosis congenita: Low regimen-related toxicity following hematopoietic cell transplantation (HCT) using a reduced intensity conditioning regimen SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Tolar, Jakub; Orchard, Paul J.; Miller, Jeffrey S.; MacMillan, Margaret L.; Wagner, John E.; Baker, K. S.] Univ Minnesota, Blood Marrow Transplant Program, Minneapolis, MN USA. [Alter, Blanche P.] Natl Canc Inst, Div Canc Epidemiol & Genet, Clin Genet Branch, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2005 BP 597A EP 597A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802527 ER PT J AU Wiestner, A Lee, E Vire, B Gibellini, F Njuguna, N Herishanu, Y Liu, D Munson, P Raghavachari, N White, T Marti, GE Wilson, WH AF Wiestner, Adrian Lee, Elinor Vire, Berengere Gibellini, Federica Njuguna, Ndegwa Herishanu, Yair Liu, Delong Munson, Peter Raghavachari, Nalini White, Therese Marti, Gerald E. Wilson, Wyndham H. TI Molecular effects of rituximab on CLL cells in vivo: Rapid increase in serum interferon gamma, induction of a distinct tumor cell gene expression signature and loss of CD20 expression SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Wiestner, Adrian; Lee, Elinor; Vire, Berengere; Gibellini, Federica; Njuguna, Ndegwa; Herishanu, Yair] NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Liu, Delong; Munson, Peter; Raghavachari, Nalini] NIH, NHLBI, Bioinformat Core, Bethesda, MD 20892 USA. [White, Therese; Wilson, Wyndham H.] NCI, CCR, Bethesda, MD 20892 USA. [Marti, Gerald E.] US FDA, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2048 BP 610A EP 610A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802570 ER PT J AU Foley, JE Mariotti, J Amarnath, S Han, S Eckhaus, M Fowler, DH AF Foley, Jason E. Mariotti, Jacopo Amarnath, Shoba Han, Soo Eckhaus, Michael Fowler, Daniel H. TI Th2.rapa cell treatment of established murine acute GVHD is abrogated by IL-2 therapy and T regulatory cells SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Foley, Jason E.; Mariotti, Jacopo; Amarnath, Shoba; Han, Soo; Eckhaus, Michael; Fowler, Daniel H.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2169 BP 645A EP 645A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802691 ER PT J AU Davis, JP Herby, S Walsh, MP Capitini, CM Guimond, M Wayne, A Fry, TJ AF Davis, Jessica P. Herby, Sarah Walsh, Meghaan P. Capitini, Christim M. Guimond, Martin Wayne, Alan Fry, Terry J. TI Extracorporeal Photopheresis diminishes graft-versus-host-diseise and modulates dendritic cell cytokine production SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Davis, Jessica P.; Herby, Sarah; Walsh, Meghaan P.; Capitini, Christim M.; Guimond, Martin; Wayne, Alan; Fry, Terry J.] NIH, NCI, CCR, Bethesda, MD USA. [Fry, Terry J.] Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2177 BP 647A EP 647A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802699 ER PT J AU Capitini, CM Herby, S Mackall, CL Fry, TJ AF Capitini, Christian. M. Herby, Sarah Mackall, Crystal L. Fry, Terry J. TI Loss of IFN gamma R1 signaling on donor bone marrow abrogates GVHD but maintains immunocompetence SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Capitini, Christian. M.; Herby, Sarah; Mackall, Crystal L.; Fry, Terry J.] NIH, NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Fry, Terry J.] Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2180 BP 648A EP 648A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802702 ER PT J AU Aerbajinai, W Zhu, JQ Gao, P Chin, K Rodgers, GP AF Aerbajinai, Wulin Zhu, Jianqiong Gao, Peter Chin, Kyung Rodgers, Griffin P. TI Mechanism for gamma-globin induction by SCIF is via PKC alpha/ERK1/2/Nrf2 dependent signal pathway to regulate down-stream transcriptional regulators NF-Y and COUP-TFII SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Aerbajinai, Wulin; Zhu, Jianqiong; Gao, Peter; Chin, Kyung; Rodgers, Griffin P.] NIH, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2194 BP 652A EP 652A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802716 ER PT J AU Chen, JC Omokaro, SO Keyvanfar, K Young, NS AF Chen, Jichun Omokaro, Stephanie O. Keyvanfar, Keyvan Young, Neal S. TI Enrichment of hematopoietic stem cells from normal and trp53 null mice using SLAM receptor CD150 as a positive selection marker SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Chen, Jichun; Omokaro, Stephanie O.; Keyvanfar, Keyvan; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2235 BP 663A EP 663A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803017 ER PT J AU Kato, GJ Cho, CS Yang, SH Bae, SW Lee, JS Gladwin, MT Rhee, SG AF Kato, Gregory J. Cho, Chun Seok Yang, Seung Ha Bae, Sung Won Lee, Jong Seo Gladwin, Mark T. Rhee, Sue Goo TI Low erythrocytic glutathion peroxidase-1 activity correlates with hemolytic rate in patients with sickle cell disease and is elevated on hydroxyurea SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Kato, Gregory J.; Gladwin, Mark T.] NIH, NHLBI, Ctr Clin, Vasc Med Branch, Bethesda, MD 20892 USA. [Cho, Chun Seok; Yang, Seung Ha; Bae, Sung Won; Rhee, Sue Goo] Ewha Womans Univ, Div Mol Life Sci, Seoul, South Korea. [Lee, Jong Seo] Ab Frontier Co Ltd, Seoul, South Korea. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2253 BP 668A EP 668A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803035 ER PT J AU Arleta, M Campbell, AD Minniti, C Ensing, G Sable, C Rana, S Darbari, D Onyinye, O Kato, GJ Gladwin, MT Castro, OL Gordeuk, VR AF Arleta, Manuel Campbell, Andrew D. Minniti, Caterina Ensing, Greg Sable, Craig Rana, Sohail Darbari, D. Onyinye, Onyekwere Kato, Greg J. Gladwin, Mark T. Castro, Oswald. L. Gordeuk, Victor R. TI Pulmonary function tests and their correlation with tricuspid regurgitant jet velocity in pediatric sickle cell disease patients SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Arleta, Manuel; Campbell, Andrew D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Gladwin, Mark T.] NIH, NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Sable, Craig] Childrens Natl Med Ctr, Div Cardiol, Washington, DC 20010 USA. [Ensing, Greg] Univ Michigan, Div Pediat Cardiol, Ann Arbor, MI 48109 USA. [Rana, Sohail; Onyinye, Onyekwere; Castro, Oswald. L.; Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2262 BP 670A EP 671A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100803044 ER PT J AU Hsieh, MM Wilder, J Fitzhugh, C Link, B Tisdale, JF AF Hsieh, Matthew M. Wilder, Jennifer Fitzhugh, Courtney Link, Beth Tisdale, John F. TI Results of alternative donor search in adult patients with severe sickle cell disease (SCD) eligible for hematopoietic stem cell transplantation (HSCT) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Hsieh, Matthew M.; Fitzhugh, Courtney; Link, Beth; Tisdale, John F.] NIDDK, NIH, MCHB, Bethesda, MD 20892 USA. [Wilder, Jennifer] NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2260 BP 670A EP 670A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803042 ER PT J AU Feng, XM Solomou, EE Keyvanfar, K Herndon, T Chen, J Kajigaya, S Young, NS AF Feng, Xingmin Solomou, Elena E. Keyvanfar, Keyvan Herndon, Thomas Chen, Jichun Kajigaya, Sachiko Young, Neal S. TI Rabbit ATG but not horse ATG promotes expansion of functional CD4(+)CD25(high)FoxP3 regulatory T cells in vitro SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Feng, Xingmin; Solomou, Elena E.; Keyvanfar, Keyvan; Herndon, Thomas; Chen, Jichun; Kajigaya, Sachiko; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2312 BP 684A EP 684A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803094 ER PT J AU Guimond, M Freud, AG Mao, HC Blaser, BW Lagemann, GG Vandeusen, JB Dorrance, A Ferketich, AK Cavalcanti, M Mackall, CL Caligiuri, MA AF Guimond, Martin Freud, Aharon G. Mao, Hsiaoyin C. Blaser, Bradley W. Lagemann, Gerritt Gerritt Vandeusen, Jeffrey B. Dorrance, Adrienne Ferketich, Amy K. Cavalcanti, Marta Mackall, Crystal L. Caligiuri, Michael A. TI Mechanism by which exogenous administration of FIt3 ligand (FL) expands natural killer cells In Vivo SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Guimond, Martin; Freud, Aharon G.; Mao, Hsiaoyin C.; Blaser, Bradley W.; Lagemann, Gerritt Gerritt; Vandeusen, Jeffrey B.; Dorrance, Adrienne; Ferketich, Amy K.; Cavalcanti, Marta; Caligiuri, Michael A.] Ohio State Univ, Ctr Comprehens Canc, Div Hematol Oncol, Columbus, OH 43210 USA. [Mackall, Crystal L.] Natl Canc Inst, Natl Inst Hlth, Pediat Oncol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2310 BP 684A EP 684A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803092 ER PT J AU Keats, JJ Chesi, M Kuehl, WM Bergsagel, PL AF Keats, Jonathan J. Chesi, Marta Kuehl, W. Michael Bergsagel, P. Leif TI A simple and reliable method to verify the authenticity and purity of human myeloma cell lines SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Keats, Jonathan J.; Chesi, Marta; Bergsagel, P. Leif] Mayo Clin, Ctr Comprehens Canc, Scottsdale, AZ USA. [Kuehl, W. Michael] Natl Canc Inst, Genet Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2485 BP 733A EP 733A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803267 ER PT J AU Kirschbaum, MH Zain, JM Popplewell, L Pullarkat, V Nademanee, AP Delioukina, ML Pulone, B Matsuoka, D Frankel, P James, ZA Forman, SJ Newman, E Gandara, D AF Kirschbaum, Mark H. Zain, Jasmine M. Popplewell, Leslie Pullarkat, Vinod Nademanee, Auayporn P. Delioukina, Maria L. Pulone, Bernadette Matsuoka, Deron Frankel, Paul James, Zwiebel A. Forman, Stephen J. Newman, Edward Gandara, David TI A phase 2 study of vorinostat (suberoylanilide hydroxamic acid, SAHA) in relapsed or refractory indolent non Hodgkin lymphoma. A California cancer consortium study SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Kirschbaum, Mark H.; Zain, Jasmine M.; Popplewell, Leslie; Pullarkat, Vinod; Nademanee, Auayporn P.; Delioukina, Maria L.; Pulone, Bernadette; Matsuoka, Deron; Frankel, Paul; Forman, Stephen J.; Newman, Edward] City Hosp Natl Canc Ctr, Duarte, CA USA. [Matsuoka, Deron; Frankel, Paul] Univ Calif Davis Canc Ctr, Sacramento, CA USA. [James, Zwiebel A.] Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2568 BP 757A EP 757A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803350 ER PT J AU Mohrbacher, A Gutierrez, M Murgo, AJ Kummar, S Reynolds, CP Maurer, BJ Groshen, S Vergara, L Kang, MH Yang, AS AF Mohrbacher, Ann Gutierrez, Martin Murgo, Anthony J. Kummar, Shivaani Reynolds, C. Patrick Maurer, Barry J. Groshen, Susan Vergara, Lori Kang, Min H. Yang, Allen S. TI Phase I trial of fenretinide (4-HPR) intravenous emulsion for hematologic malignancies SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Mohrbacher, Ann; Groshen, Susan; Yang, Allen S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. [Kummar, Shivaani] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Reynolds, C. Patrick; Maurer, Barry J.; Kang, Min H.] Univ So Calif, Childrens Hosp Los Angeles, Inst Pediat Clin Res, Dev Therapeut Program, Los Angeles, CA 90089 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2581 BP 761A EP 761A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803363 ER PT J AU Johnson, NA Nayar, T Dave, SS Wright, G Rosenwald, A Chan, WC Bast, M Rimsza, LM Holte, H Delabie, J Connors, JM Al-Tourah, A Colomo, L Campo, E Lister, TA O'Shea, D Staudt, LM Gascoyne, RD AF Johnson, N. A. Nayar, T. Dave, S. S. Wright, G. Rosenwald, A. Chan, W. C. Bast, M. Rimsza, L. M. Holte, H. Delabie, J. Connors, J. M. Al-Tourah, A. Colomo, L. Campo, E. Lister, T. A. O'Shea, D. Staudt, L. M. Gascoyne, Randy D. TI Gene expression model of survival and transformation in follicular lymphoma (FL): A study by the LLMPP SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Johnson, N. A.; Nayar, T.; Connors, J. M.; Al-Tourah, A.; Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Dave, S. S.; Wright, G.; Staudt, L. M.] NCI, Bethesda, MD 20892 USA. [Chan, W. C.; Bast, M.] Univ Nebraska Med Ctr, Omaha, NE USA. [Rimsza, L. M.] Univ Arizona, Ctr Canc, Tucson, AZ 85721 USA. [Holte, H.; Delabie, J.] Norwegian Radium Hosp, Oslo, Norway. [Rosenwald, A.] Univ Wurzburg, Wurzburg, Germany. [Colomo, L.; Campo, E.] Univ Barcelona, Barcelona 7, Spain. [O'Shea, D.] St Bartholomews Hosp, Canc Res UK, London, England. RI Colomo, Luis/A-2259-2016 OI Colomo, Luis/0000-0001-5236-5085 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2606 BP 767A EP 767A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803388 ER PT J AU Anderson, LA Pfeiffer, R Warren, J Landgren, O Berndt, S Gadalla, S Ricker, W Parsons, R Engels, EA AF Anderson, Lesley A. Pfeiffer, Ruth Warren, Joan Landgren, Ola Berndt, Sonja Gadalla, Shahinaz Ricker, Winnie Parsons, Ruth Engels, Eric A. TI Hepatitis B and C virus in patients with Non-Hodgkin lymphoma SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Anderson, Lesley A.; Pfeiffer, Ruth; Warren, Joan; Landgren, Ola; Berndt, Sonja; Gadalla, Shahinaz; Engels, Eric A.] NIH, NCI, Bethesda, MD 20892 USA. [Ricker, Winnie; Parsons, Ruth] IMS, Informat Management Serv, Rockville, MD USA. RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2627 BP 773A EP 774A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100803409 ER PT J AU Lenz, G Wright, GW Dave, S Xiao, WM Powell, J Rosenwald, A Muller-Hermelink, HK Gascoyne, RD Connors, JM Campo, E Jaffe, ES Delabie, J Smeland, EB Rimsza, L Fisher, RI Chan, WC Staudt, LM AF Lenz, Georg Wright, George W. Dave, Sandeep Xiao, Wenming Powell, John Rosenwald, Andreas Muller-Hermelink, Hans-Konrad Gascoyne, Randy D. Connors, Joseph M. Campo, Elias Jaffe, Elaine S. Delabie, Jan Smeland, Erlend B. Rimsza, Lisa Fisher, Richard I. Chan, Wing C. Staudt, Louis M. TI Distinct genetic aberrations in molecular subtypes of diffuse large B cell lymphoma detected by array CGH. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Lenz, Georg; Wright, George W.; Dave, Sandeep; Xiao, Wenming; Powell, John; Jaffe, Elaine S.; Staudt, Louis M.] NCI, Canc Res Ctr, Bethesda, MD 20892 USA. [Rosenwald, Andreas; Muller-Hermelink, Hans-Konrad] Univ Wurzburg, D-97070 Wurzburg, Germany. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Campo, Elias] Univ Barcelona, E-08007 Barcelona, Spain. [Delabie, Jan; Smeland, Erlend B.] Norwegian Radium Hosp, Oslo, Norway. [Rimsza, Lisa] Univ Arizona, Tucson, AZ 85721 USA. [Chan, Wing C.] Univ Nebraska, Lincoln, NE 68583 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2631 BP 774A EP 775A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100803413 ER PT J AU Aue, G Du, Y Jenkins, NA Dunbar, CE Copeland, NG AF Aue, Georg Du, Yang Jenkins, Nancy A. Dunbar, Cynthia E. Copeland, Neal G. TI PU.1 cooperates with SOX4 in myeloid cells. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Aue, Georg; Dunbar, Cynthia E.] NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Aue, Georg; Du, Yang; Jenkins, Nancy A.; Copeland, Neal G.] NIH, NCI, Mouse Canc Genet Program, Frederick, MD USA. [Jenkins, Nancy A.; Copeland, Neal G.] Natl Univ Singapore, Inst Mol & Cell Biol, Canc Genet Lab, Singapore 117548, Singapore. [Du, Yang] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2633 BP 775A EP 775A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803415 ER PT J AU Choi, CW Chung, YJ Slape, C Aplan, PD AF Choi, Chul Won Chung, Yang Jo Slape, Christopher Aplan, Peter D. TI A NUP98-HOXD13 fusion gene impairs differentiation of T and B lymphocytes SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Choi, Chul Won; Chung, Yang Jo; Slape, Christopher; Aplan, Peter D.] NCI, NIH, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA. RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016 OI Slape, Christopher/0000-0002-8407-3092; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2650 BP 779A EP 780A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100803432 ER PT J AU Ozpolat, B Akar, U Colburn, NH Lopez-Berestein, G AF Ozpolat, Bulent Akar, Ugur Colburn, Nancy H. Lopez-Berestein, Gabriel TI Novel tumor suppressor protein programmed cell death 4 (PDCD4) suppresses activity of PI3K/Akt pathway and regulates expression of p27 (Kip1) and c-myc, DAP5 and Willm's tumor (WT1) in acute myeloid leukemia SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Ozpolat, Bulent; Akar, Ugur; Lopez-Berestein, Gabriel] MD Anderson Canc Ctr, Houston, TX USA. [Colburn, Nancy H.] NCI, Ctr Canc Res, Gene Regulat Sect, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2656 BP 781A EP 781A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803438 ER PT J AU Chattopadhyay, R Iacob, R Majumder, R Tomer, KB Lentz, BR AF Chattopadhyay, Rima Iacob, Roxana Majumder, Rinku Tomer, Kenneth B. Lentz, Barry R. TI Functional and structural characterization of factor Xa dimer in solution SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Chattopadhyay, Rima; Majumder, Rinku; Lentz, Barry R.] Univ N Carolina, Dept Biochem & Biophys, Program Mol & Cellular Biophys, Chapel Hill, NC USA. [Iacob, Roxana; Tomer, Kenneth B.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2698 BP 792A EP 792A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803480 ER PT J AU Berg, M Lundqvist, A Fan, Y McCoy, JP Yokoyama, H Childs, R AF Berg, Maria Lundqvist, Andreas Fan, Yong McCoy, J. Philip Yokoyama, Hisayuki Childs, Richard TI In vitro-expanded NK cells have increased TRAIL and NKG2D expression and enhanced TRAIL-mediated tumor cytotoxicity compared to non-expanded NK cells SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Berg, Maria; Lundqvist, Andreas; Yokoyama, Hisayuki; Childs, Richard] NIH, NHLBI, Hematol Branch, Bethesda, MD USA. [McCoy, J. Philip] NIH, NHLBI, Flow Cytometry Core Facil, Bethesda, MD USA. [Fan, Yong] NIH, Dept Transfus Med, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2744 BP 806A EP 806A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803526 ER PT J AU Melenhorst, JJ Scheinberg, P Chattopadhyay, PK Gostick, E Roederer, M Hensel, NF Douek, DC Barrett, AJ Price, DA AF Melenhorst, J. Jopseph Scheinberg, Phillip Chattopadhyay, Pratip K. Gostick, Emma Roederer, Mario Hensel, Nancy F. Douek, Daniel C. Barrett, A. John Price, David A. TI High avidity leukemia-associated antigen-specific CD8(+) T cells preferentially localize to the bone marrow in patients with myeloid malignancies SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Melenhorst, J. Jopseph; Scheinberg, Phillip; Hensel, Nancy F.; Barrett, A. John] NHLBI, NIH, Bethesda, MD 20892 USA. [Scheinberg, Phillip; Douek, Daniel C.; Price, David A.] NIAID, Vaccine Res Ctr, NIH, Human Immunol Sect, Bethesda, MD 20892 USA. [Chattopadhyay, Pratip K.; Roederer, Mario] NIAID, NIH, Vaccine Res Ctr, Immunotechnol Sect, Bethesda, MD 20892 USA. [Gostick, Emma; Price, David A.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2763 BP 811A EP 812A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100803545 ER PT J AU Grady, RW Bakke, J Steinmetz, K Bishop, TR Hedlund, BE AF Grady, Robert W. Bakke, James Steinmetz, Karen Bishop, Terry R. Hedlund, Bo E. TI Pharmacokinetic and toxicological results of a 28-day multiple dose study of starch-conjugated deferoxantine (S-DFO, 40SD02) in iron-loaded dogs SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Grady, Robert W.] Weill Med Coll, New York, NY USA. [Bakke, James; Steinmetz, Karen] SRI Int, Biosci Div, Menlo Pk, CA USA. [Bishop, Terry R.] NIDDK, Hematol Program, Bethesda, MD USA. [Hedlund, Bo E.] Biomed Frontiers, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2780 BP 817A EP 817A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803562 ER PT J AU Rizzatti, FG Stroncek, D Qazi, M Sibmooh, N Piknova, B Schechter, AN AF Rizzatti, Fabiola G. Stroncek, David Qazi, Melissa Sibmooh, Nathawut Piknova, Barbora Schechter, Alan N. TI Effect of storage on levels of nitric oxide derivatives in blood components SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Rizzatti, Fabiola G.; Qazi, Melissa; Sibmooh, Nathawut; Piknova, Barbora; Schechter, Alan N.] Natl Inst Hlth, NIDDK, Mol Med Branch, Bethesda, MD USA. [Stroncek, David] Ctr Clin, Natl Inst Hlth, Div Transfus Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2884 BP 849A EP 849A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803666 ER PT J AU Srinivasan, R Hedlin, H Goovin, R Smith, A Ramos, C Cook, L Bolan, C Yokoyama, H Srivastava, S Karpovich, J Bonohue, T Barren, J Geller, N Childs, R AF Srinivasan, Ramaprasad Hedlin, Haley Goovin, Rose Smith, Aleah Ramos, Catalina Cook, Lisa Bolan, Charles Yokoyama, Hisayuki Srivastava, Shivani Karpovich, Jennifer Bonohue, Teresa Barren, John Geller, Nancy Childs, Richard TI Reduced incidence of acute Graft versus host disease (GVHD) and transplant-related mortality (TRM) with the addition of short-course mini-dose methotrexate (MTX) to cyclosporine (CSA) as GVHD prophylaxis following nonmyeloablative hematopoietic stem cell transplantation (NST) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Srinivasan, Ramaprasad] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Hedlin, Haley] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Goovin, Rose; Smith, Aleah; Ramos, Catalina; Yokoyama, Hisayuki; Srivastava, Shivani; Karpovich, Jennifer; Bonohue, Teresa; Barren, John; Childs, Richard] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Bolan, Charles] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2990 BP 878A EP 878A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804027 ER PT J AU Pasquini, MC Ewell, M Stadtmauer, EA Bredeson, CN Alyea, EP Stockerl-Goldstein, K Krishnan, A Sahebi, F Rowley, SD Maloney, DG Vesole, DH Horowitz, MM Carter, S Geller, N Giralt, S AF Pasquini, Marcelo C. Ewell, Marian Stadtmauer, Edward A. Bredeson, Christopher N. Alyea, Edwin P. Stockerl-Goldstein, Keith Krishnan, Amrita Sahebi, Firoozeh Rowley, Scott D. Maloney, David G. Vesole, David H. Horowitz, Mary M. Carter, Shelly Geller, Nancy Giralt, Sergio TI Biologic assignment clinical trials in hematopoietic stem cell transplantation (HSCT) for multiple myeloma: Baseline characteristics by treatment allocation from BMT CTN 0102 according to availability of an HLA-matched sibling donor SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Pasquini, Marcelo C.; Horowitz, Mary M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Stadtmauer, Edward A.] Univ Penn, Philadelphia, PA 19104 USA. [Alyea, Edwin P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Stockerl-Goldstein, Keith] Stanford Univ, Stanford, CA 94305 USA. [Rowley, Scott D.] Hackensack Univ, Hackensack, NJ USA. [Maloney, David G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Geller, Nancy] NHLBI, Bethesda, MD 20892 USA. [Giralt, Sergio] MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3028 BP 889A EP 889A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804065 ER PT J AU Landgren, O Albitar, MX Ma, WX Abbasi, FR Hayes, RB Marti, GE Caporaso, NE AF Landgren, Ola Albitar, Maher X. Ma, Wanlong X. Abbasi, Fatima R. Hayes, Richard B. Marti, Gerald E. Caporaso, Neil E. TI Evidence of pre-diagnostic monoclonality in blood obtained up to 6.4 years preceding diagnosis of chronic lymphocytic leukemia (CLL) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Landgren, Ola; Hayes, Richard B.; Caporaso, Neil E.] Natl Canc Inst, NIH, Bethesda, MD USA. [Albitar, Maher X.; Ma, Wanlong X.] Nichols Inst Quest Diagnost, San Juan Capistrano, CA USA. [Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3082 BP 906A EP 907A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100804119 ER PT J AU Skupsky, J Lozier, JN Donahue, RE Metzger, MN Azimzadeh, GM Pierson, RN Scott, DW AF Skupsky, Jonathan Lozier, Jay N. Donahue, Robert E. Metzger, Mark N. Azimzadeh, Agnes M. Pierson, Richard N., III Scott, David W. TI Immunogenicity of human factor VIR in rhesus and cynomolgus monkeys SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Skupsky, Jonathan; Scott, David W.] Univ Maryland, Sch Med, Ctr Vasc & Inflammat Dis, Baltimore, MD USA. [Lozier, Jay N.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD USA. [Donahue, Robert E.; Metzger, Mark N.] Natl Inst Hlth, NHLBI, Hematol Branch, Bethesda, MD USA. [Azimzadeh, Agnes M.; Pierson, Richard N., III; Scott, David W.] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD USA. [Scott, David W.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3148 BP 925A EP 926A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100804185 ER PT J AU Lemery, SJ Hsieh, MM Smith, A Rao, S Khuu, HM Theresa, D Karpovich, JM Cook, L Goodwin, R Boss, C Calandra, G Geller, N Tisdale, J Childs, R AF Lemery, Steven J. Hsieh, Matthew M. Smith, Aleah Rao, Sheila Khuu, Hanh M. Theresa, Donohue Karpovich, Jennifer M. Cook, Lisa Goodwin, Rose Boss, Carol Calandra, Gary Geller, Nancy Tisdale, John Childs, Richard TI A pilot study evaluating the CD34(+) cell, mobilizing activity and adverse events associated with escalating doses of AMD3100 in healthy volunteers SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Lemery, Steven J.; Smith, Aleah; Rao, Sheila; Theresa, Donohue; Karpovich, Jennifer M.; Cook, Lisa; Goodwin, Rose; Boss, Carol; Geller, Nancy; Childs, Richard] NHLBI, NIH, Bethesda, MD USA. [Hsieh, Matthew M.; Tisdale, John] NIDDK, NIH, Bethesda, MD USA. [Khuu, Hanh M.] DTM, NIH, Bethesda, MD USA. [Calandra, Gary] Genzyme, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3278 BP 962A EP 963A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100804315 ER PT J AU Smith, AL Jungnam, J Rao, S Lundqvist, A Cook, LW Goodwin, RS Ramos, C Geller, NL Childs, RW AF Smith, Aleah L. Jungnam, Joo Rao, Sheila Lundqvist, Andreas Cook, Lisa W. Goodwin, Rose S. Ramos, Catalina Geller, Nancy L. Childs, Richard W. TI Significant alterations in T-Cell TH1 and TH2 cytokine gene profiles associated with G-CSF mobilization do not occur in T-Cells mobilized with AMD3100 SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Smith, Aleah L.; Rao, Sheila; Lundqvist, Andreas; Cook, Lisa W.; Goodwin, Rose S.; Ramos, Catalina; Childs, Richard W.] NHLBI, Natl Inst Hlth, Bethesda, MD USA. [Jungnam, Joo; Geller, Nancy L.] NHLBI, Natl Inst Hlth, Off Biostat Res, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3277 BP 962A EP 962A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804314 ER PT J AU Mielke, S Nunes, R Rezvani, K Fellowes, VS Venne, A Solomon, SR Fan, Y Scotto, C Read, EJ Barret, AJ AF Mielke, Stehan Nunes, Raquel Rezvani, Katayoun Fellowes, Vicki S. Venne, Annie Solomon, Scott R. Fan, Yong Scotto, Christian Read, Elizabeth J. Barret, A. John TI Successful translation of a GMP-Based, clinical scale selective allodepletion approach for matched donor-recipient pairs from bench-to-bedside. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Mielke, Stehan; Nunes, Raquel; Rezvani, Katayoun; Solomon, Scott R.; Fan, Yong; Barret, A. John] NHLBI, NIH, Hematol Branch, Allotransplantat Sect, Bethesda, MD USA. [Fellowes, Vicki S.; Read, Elizabeth J.] NIH, Dept Transfus Med, Cell Proc Sect, Bethesda, MD USA. [Venne, Annie; Scotto, Christian] Kiadis Pharma Inc, St Laurent, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3279 BP 963A EP 963A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804316 ER PT J AU Vasu, S Yau, YY Tisdale, JF Hsieh, M Childs, RW Barrett, AJ Fowler, D Bishop, MR Kang, E Malech, HL Dunbar, CE Leitiman, SF Bolan, CD AF Vasu, Sumithira Yau, Yu Y. Tisdale, John F. Hsieh, Matthew Childs, Richard W. Barrett, A. John Fowler, Daniel Bishop, Michael R. Kang, Elizabeth Malech, Harry L. Dunbar, Cynthia E. Leitiman, Susan F. Bolan, Charles D. TI Factors affecting allogeneic peripheral blood stem cell mobilization in a large, ethnically, diverse population SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Tisdale, John F.; Hsieh, Matthew] NIDDK, Hematol Branch, Bethesda, MD 20892 USA. [Childs, Richard W.; Barrett, A. John; Dunbar, Cynthia E.; Bolan, Charles D.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Fowler, Daniel; Bishop, Michael R.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Kang, Elizabeth; Malech, Harry L.] NIAID, NIH, Host Def Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3283 BP 964A EP 964A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804320 ER PT J AU Boxer, LA Bolyard, AA Newburger, PE Bonilla, MA Kannourakis, G Dror, Y Link, DC Alter, BP Rosenberg, PS Dale, DC AF Boxer, Laurence A. Bolyard, Audrey Anna Newburger, Peter E. Bonilla, Mary Ann Kannourakis, George Dror, Yigal Link, Daniel C. Alter, Blanche P. Rosenberg, Philip S. Dale, David C. TI Predictors of transformation to myelodysplasia/acute myelogenous leukemia (MDS/AML) in severe congenital neutropenia (CN) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Boxer, Laurence A.] Univ Michigan, Womens Hosp, Ann Arbor, MI 48109 USA. [Bolyard, Audrey Anna; Dale, David C.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Newburger, Peter E.] Univ Massachusetts, Med Ctr, Worcester, MA 01605 USA. [Bonilla, Mary Ann] St Josephs Childrens Hosp, Paterson, NJ USA. [Kannourakis, George] Univ Ballarat, Ballarat Onc & Haem Serv, Wendouree, Vic, Australia. [Dror, Yigal] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Link, Daniel C.] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. [Alter, Blanche P.] NCI, Clin Genet Branch, Bethesda, MD 20892 USA. [Rosenberg, Philip S.] NCI, Biostat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3307 BP 971A EP 971A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804344 ER PT J AU Dale, DC Bolyard, AA Newburger, PE Bonilla, MA Kannourakis, G Dror, Y Link, DC Alter, BP Rosenberg, PS Boxer, LA AF Dale, David C. Bolyard, Audrey Anna Newburger, Peter E. Bonilla, Mary Ann Kannourakis, George Dror, Yigal Link, Daniel C. Alter, Blanche P. Rosenberg, Philip S. Boxer, Laurence A. TI Cyclic neutropenia is not associated with transformation to MDS and AML SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Dale, David C.; Bolyard, Audrey Anna] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Newburger, Peter E.] Univ Massachusetts, Med Ctr, Worcester, MA USA. [Bonilla, Mary Ann] St Josephs Childrens Hosp, Paterson, NJ USA. [Kannourakis, George] Univ Ballarat, Ballarat Oncol & Haem Serv, Wendouree, Vic, Australia. [Dror, Yigal] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Link, Daniel C.] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. [Alter, Blanche P.] NCI, Clin Genet Branch, Bethesda, MD 20892 USA. [Rosenberg, Philip S.] NCI, Biostat Branch, Bethesda, MD 20892 USA. [Boxer, Laurence A.] Univ Michigan, Womens Hosp, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3306 BP 971A EP 971A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804343 ER PT J AU Metais, JY Dunfee, AE Calado, RT Dunbar, CE AF Metais, Jean-Yves Dunfee, Ashley E. Calado, Rodrigo T. Dunbar, Cynthia E. TI BCL2A1 is a survival and immortalization factor for primitive myeloid hematopoietic cells SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Metais, Jean-Yves; Dunfee, Ashley E.; Calado, Rodrigo T.; Dunbar, Cynthia E.] NIH, NHLBI, Hematol Branch, Bethesda, MD USA. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3365 BP 987A EP 987A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804402 ER PT J AU Hyde, RK Kreycik, CE Liu, PP AF Hyde, R. Katherine Kreycik, Claire E. Liu, Pu Paul TI CBFB-independent activities of the inv(16) fusion gene CBFB-MYH11 SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Hyde, R. Katherine; Kreycik, Claire E.; Liu, Pu Paul] NIH, NHGRI, Bethesda, MD USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3376 BP 989A EP 990A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100804413 ER PT J AU Campbell, AD Minniti, C Sable, C Ensing, D Dham, N Rana, S Darbari, D Onyekwere, O Kato, GJ Gladwin, MT Castro, O Gordeuk, V AF Campbell, Andrew D. Minniti, Caterina Sable, Craig Ensing, Dreg Dham, Niti Rana, Sohail Darbari, D. Onyekwere, Onyinye Kato, Greg J. Gladwin, Mark T. Castro, Oswaldo Gordeuk, Victor TI Prospective evaluation of the prevalence of elevated tricuspid regurgitant jet velocity and associated clinical and echocardiographic factors in children and adolescents with sickle cell disease SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Campbell, Andrew D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Rana, Sohail; Onyekwere, Onyinye; Castro, Oswaldo; Gordeuk, Victor] Howard Univ, Ctr Sickle Cell Dis, Washington, DC USA. [Kato, Greg J.; Gladwin, Mark T.] NIH, NHLBI, Vasc Med Branch, Bethesda, MD USA. [Sable, Craig; Dham, Niti] Childrens Natl Med Ctr, Div Cardiol, Washington, DC USA. [Minniti, Caterina; Darbari, D.] Childrens Natl Med Ctr, Div Hematol, Washington, DC USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3388 BP 993A EP 993A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804425 ER PT J AU Kumkhaek, C Zhu, J Taylor, JG Hoppe, C Kato, GJ Rodgers, GP AF Kumkhaek, Chutima Zhu, Jianqiong Taylor, James G. Hoppe, Carolyn Kato, Gregory J. Rodgers, Griffin P. TI Variation in the small guanosine triphosphate (GTP)-binding protein, secretion-associated and RAS-related (SAR1A) gene and response to hydroxyurea treatment in sickle cell disease SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Kumkhaek, Chutima; Zhu, Jianqiong; Rodgers, Griffin P.] NIH, NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA. [Taylor, James G.; Kato, Gregory J.] NIH, NHLBI, Vasc Med Branch, Bethesda, MD USA. [Hoppe, Carolyn] Childrens Hosp & Res Ctr Oakland, Dept Hematol Oncol, Oakland, CA USA. [Kato, Gregory J.] NIH, Ctr Clin, Crit Care Med, Bethesda, MD USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3392 BP 994A EP 994A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804429 ER PT J AU Little, JA Hauser, KP Martyr, SE Kato, GJ Machado, R Castro, O Taylor, J Gladwin, MT AF Little, Jane A. Hauser, Kristina Partovi Martyr, Sabrina E. Kato, Gregory J. Machado, Roberto Castro, Oswaldo Taylor, James Gladwin, Mark T. TI Phosphodiesterase inhibition increases fetal hemoglobin in sickle cell disease; L-arginine supplementation does not SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Little, Jane A.; Martyr, Sabrina E.; Kato, Gregory J.; Machado, Roberto; Taylor, James; Gladwin, Mark T.] Natl Inst Hlth, NHLBI, Pulm & Vasc Med Branch, Bethesda, MD USA. [Hauser, Kristina Partovi] Natl Inst Hlth, NHLBI, Crit Care Med Branch, Bethesda, MD USA. [Castro, Oswaldo] Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3396 BP 995A EP 995A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804433 ER PT J AU Mulkerin, D Remick, S Takimoto, C Ivy, P Karol, M Eton, O AF Mulkerin, Daniel Remick, Scot Takimoto, Chris Ivy, Percy Karol, Michael Eton, Omar TI Safety, tolerability, and pharmacology of bortezomib in cancer patients with renal failure requiring dialysis: Results from a prospective phase I study SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Mulkerin, Daniel] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI USA. [Remick, Scot] W Virginia Univ, Morgantown, WV 26506 USA. [Takimoto, Chris] S Texas Accelerated Res Therapeut, San Antonio, TX USA. [Ivy, Percy] NCI, CTEP, Rockville, MD USA. [Karol, Michael; Eton, Omar] Millennim Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3477 BP 1018A EP 1019A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100804514 ER PT J AU O'Mahony, D Morris, JC Stetler-Stevenson, M Matthews, H Pittaluga, S Albert, P Kaucic, K Hammershaimb, L Waldmann, TA Janik, JE AF O'Mahony, Deirdre Morris, John C. Stetler-Stevenson, Maryalice Matthews, Helen Pittaluga, Stefania Albert, Paul Kaucic, Karen Hammershaimb, Luz Waldmann, Thomas A. Janik, John E. TI EBV-related lymphoproliferative disease complicating therapy with siplizumab, a novel anti-CD2 mediated t- and NK-cell depleting agent, in patients with T-cell malignancies SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [O'Mahony, Deirdre; Morris, John C.; Janik, John E.] Natl Canc Inst, Metab Branch, Bethesda, MD USA. [Stetler-Stevenson, Maryalice; Pittaluga, Stefania] Natl Canc Inst, Pathol Lab, Bethesda, MD USA. [Albert, Paul] Natl Canc Inst, Biol Res Branch, Bethesda, MD USA. [Kaucic, Karen; Hammershaimb, Luz] MedImmune Inc, Gaithersburg, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3565 BP 1043A EP 1043A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804602 ER PT J AU Anastasov, N Rudelius, M Klier, M Dau, T Angermeier, D Pittaluga, S Duyster, J Fend, F Raffeld, M Quintanilla-Martinez, L AF Anastasov, Natasa Rudelius, Martina Klier, Margit Dau, Therese Angermeier, Damela Pittaluga, Stefania Duyster, Justus Fend, Falko Raffeld, Mark Quintanilla-Martinez, Leticia TI C/EBP beta expression in ALK plus anaplastic large cell lymphomas (ALCL) is regulated by Stat3 signaling pathway SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Anastasov, Natasa; Klier, Margit; Dau, Therese; Quintanilla-Martinez, Leticia] GSF Res Ctr Hlth & Environm, Inst Pathol, Munich, Germany. [Rudelius, Martina; Angermeier, Damela; Fend, Falko] Tech Univ Munich, Inst Pathol, Munich, Germany. [Duyster, Justus] Tech Univ Munich, Munich, Germany. [Pittaluga, Stefania; Raffeld, Mark] Natl Inst Hlth, Natl Canc Inst, Pathol Lab, Hematol Sect, Bethesda, MD USA. RI Anastasov, Natasa/M-9848-2014 OI Anastasov, Natasa/0000-0002-4088-1119 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3570 BP 1044A EP 1044A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804607 ER PT J AU Bluhm, EC Ronckers, C Hayashi, RJ Neglia, JP Mertens, AC Meadows, AT Milby, P Stovall, M Robison, LL Inskip, PD AF Bluhm, Elizabeth C. Ronckers, Cecile Hayashi, Robert J. Neglia, Joseph P. Mertens, Ann C. Meadows, Anna T. Milby, PaulineA. Stovall, Marilyn Robison, Leslie L. Inskip, Peter D. TI Cause-specific mortality and second cancer incidence after non-Hodgkin lymphoma: A report from the childhood cancer survivor study SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Bluhm, Elizabeth C.; Ronckers, Cecile] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Ronckers, Cecile] Emma Childrens Hosp, Dept Pediat Oncol, Amsterdam, Netherlands. [Hayashi, Robert J.] Washington Univ, Sch Med, Div Pediat Hematol & Oncol, St Louis, MO 63130 USA. [Neglia, Joseph P.; Milby, PaulineA.] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. [Mertens, Ann C.] Emory Childrens Ctr, Aflac Canc Ctr, Blood Disorders Serv, Atlanta, GA 30322 USA. [Meadows, Anna T.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr Houston, Dept Radiat Phys, Houston, TX USA. [Robison, Leslie L.] St Jude Childrens Hosp, Dept Epidemiol & Canc control, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3579 BP 1047A EP 1047A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804616 ER PT J AU Beleslin-Cokic, BB Cokic, VP Gojkovic-Bukarica, L Noguchi, CT AF Beleslin-Cokic, Bojana B. Cokic, Vladan P. Gojkovic-Bukarica, Ljiljana Noguchi, Constance Tom TI Erythropoietin signaling and response in vascular smooth muscle cells. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Beleslin-Cokic, Bojana B.] Inst Endocrinol Diabet & Metab Dis, Dept Genet, Belgrade, Serbia. [Cokic, Vladan P.] Med Res Inst, Lab Expt Hematol, Belgrade, Serbia. [Gojkovic-Bukarica, Ljiljana] Inst Pharmacol, Dept Pharmacol, Belgrade, Serbia. [Noguchi, Constance Tom] NIH, NIDDK, Mol Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3724 BP 1087A EP 1087A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804761 ER PT J AU Harrow, F Battle, S Seidel, NE Cline, AP Gallagher, PG Bodine, DM AF Harrow, Faith Battle, Stephanie Seidel, Nancy E. Cline, Amanda P. Gallagher, Patrick G. Bodine, David M. TI Characterization of regulatory elements in the Slc4a1 (Band 3) locus to create safe and effective vectors for globin gene therapy SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Harrow, Faith; Battle, Stephanie; Seidel, Nancy E.; Cline, Amanda P.; Bodine, David M.] NHGRI, GMBB, Hematopoiesis Sect, Bethesda, MD 20892 USA. [Gallagher, Patrick G.] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3740 BP 1091A EP 1091A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804777 ER PT J AU Laflamme, K Elnitski, LE Wong, C Mary, Y Gallagher, PG Bodine, DM AF Laflamme, Karina Elnitski, Laura E. Wong, Clara Mary, Yang Gallagher, Patrick G. Bodine, David M. TI Identification of a TFIID binding sequence that increases expression from the ankyrin-1 promoter: Application to globin gene therapy SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Laflamme, Karina; Bodine, David M.] NHGRI, GMBB, Hematopoiesis Sect, Bethesda, MD 20892 USA. [Elnitski, Laura E.; Mary, Yang] NHGRI, GTB, Genom Func Anal Sect, Bethesda, MD 20892 USA. [Wong, Clara; Gallagher, Patrick G.] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3741 BP 1091A EP 1092A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100804778 ER PT J AU Bauer, TR Hai, M Adler, RL Allen, JM Tuschong, LM Olson, EM Hickstein, DD Russell, DW AF Bauer, Thomas R., Jr. Hai, Mehreen Adler, Rima L. Allen, James M. Tuschong, Laura M. Olson, Erik M. Hickstein, Dennis D. Russell, David W. TI Reduced genotoxic risk using foamy viral vectors for the treatment of canine leukocyte adhesion deficiency SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Bauer, Thomas R., Jr.; Hai, Mehreen; Adler, Rima L.; Tuschong, Laura M.; Hickstein, Dennis D.] NIH, Natl Canc Inst, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Allen, James M.; Olson, Erik M.; Russell, David W.] Univ Washington, Dept Hematol, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3744 BP 1092A EP 1092A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804781 ER PT J AU Washington, K Phang, OJ Hsieh, M Tisdale, JF AF Washington, Kareem Phang, O. J. Hsieh, Matt Tisdale, John F. TI Innate immune factors are expressed among peripheral blood CD34(+) HSCs, are induced upon exposure to lentiviral vectors and may limit transduction efficiency SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Washington, Kareem; Phang, O. J.; Hsieh, Matt; Tisdale, John F.] NIH, NIDDK, MCHB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3743 BP 1092A EP 1092A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804780 ER PT J AU Xie, JX Larochelle, A Faulhaber, M Donahue, RE Dunbar, CE AF Xie, Jianjun Xie Larochelle, Andre Faulhaber, Marion Donahue, Robert E. Dunbar, Cynthia E. TI Repetitive busulfan administration uncovers a competitive advantage for hematopoietic clones with a retrovirus insertion near the HDAC7A locus SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Xie, Jianjun Xie; Larochelle, Andre; Donahue, Robert E.; Dunbar, Cynthia E.] Natl Inst Hlth, NHLBI, Hematol Branch, Bethesda, MD USA. [Faulhaber, Marion] Natl Inst Hlth, NIA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3745 BP 1092A EP 1093A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100804782 ER PT J AU Caceres, JF Misteli, T AF Caceres, Javier F. Misteli, Tom TI Division of labor: Minor splicing in the cytoplasm SO CELL LA English DT Editorial Material ID SPLICEOSOME; PROTEINS; INTRONS; U12 AB There are two molecular machineries for pre-mRNA splicing - the major spliceosome and the minor spliceosome. In this issue of Cell, Konig et al. (2007) demonstrate that the two splicing pathways are spatially separated in the cell and may have distinct functions. C1 MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland. NCI, NIH, Bethesda, MD 20892 USA. RP Caceres, JF (reprint author), MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland. EM javier.caceres@hgu.mrc.ac.uk; mistelit@mail.nih.gov RI Caceres, Javier/D-5260-2013 OI Caceres, Javier/0000-0001-8025-6169 FU Medical Research Council [MC_U127584479] NR 9 TC 6 Z9 6 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 16 PY 2007 VL 131 IS 4 BP 645 EP 647 DI 10.1016/j.cell.2007.11.001 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 231RI UT WOS:000250966300009 PM 18022356 ER PT J AU Renda, M Baglivo, I Burgess-Beusse, B Esposito, S Fattorusso, R Felsenfeld, G Pedone, PV AF Renda, Mario Baglivo, Ilaria Burgess-Beusse, Bonnie Esposito, Sabrina Fattorusso, Roberto Felsenfeld, Gary Pedone, Paolo V. TI Critical DNA binding interactions of the insulator protein CTCF - A small number of zinc fingers mediate strong binding, and a single finger-DNA interaction controls binding at imprinted loci SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENHANCER-BLOCKING ACTIVITY; HUMAN GENOME; GENE; PROMOTER; H19; METHYLATION; DOMAIN; TRANSCRIPTION; BOUNDARIES; REPRESSOR AB The DNA-binding protein CTCF (CCCTC binding factor) mediates enhancer blocking insulation at sites throughout the genome and plays an important role in regulating allele-specific expression at the Igf2/H19 locus and at other imprinted loci. Evidence is also accumulating that CTCF is involved in large scale organization of genomic chromatin. Although CTCF has 11 zinc fingers, we show here that only 4 of these are essential to strong binding and that they recognize a core 12-bp DNA sequence common to most CTCF sites. By deleting individual fingers and mutating individual sites, we determined the orientation of binding. Furthermore, we were able to identify the specific finger and its point of DNA interaction that are responsible for the loss of CTCF binding when CpG residues are methylated in the imprinted Igf2/H19 locus. This single interaction appears to be critical for allele-specific binding and insulation by CTCF. C1 NIDDK, NIH, Mol Biol Lab, Bethesda, MD 20892 USA. Univ Naples 2, Dipartimento Sci Ambientali, I-81100 Caserta, Italy. RP Felsenfeld, G (reprint author), NIDDK, NIH, Mol Biol Lab, Bldg 5 Rm 212, Bethesda, MD 20892 USA. EM gary.felsenfeld@nih.gov; paolov.pedone@unina2.it OI Fattorusso, Roberto/0000-0002-3539-5343 FU Intramural NIH HHS NR 32 TC 77 Z9 80 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2007 VL 282 IS 46 BP 33336 EP 33345 DI 10.1074/jbc.M706213200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229XP UT WOS:000250840200013 PM 17827499 ER PT J AU Monterroso, B Minton, AP AF Monterroso, Begona Minton, Allen P. TI Effect of high concentration of inert cosolutes on the refolding of an enzyme - Carbonic anhydrase B in sucrose and Ficoll 70 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SELF-ASSOCIATION; GLOBULAR-PROTEINS; STABILITY; CONSEQUENCES; DEXTRAN; STATE; AGGREGATION; DNA AB The kinetics of refolding of carbonic anhydrase II following transfer from a buffer containing 5 M guanidinium chloride to a buffer containing 0.5 M guanidinium chloride were studied by measuring the time-dependent recovery of enzymatic activity. Experiments were carried out in buffer containing concentrations of two "inert" cosolutes, sucrose and Ficoll 70, a sucrose polymer, at concentrations up to 150 g/liter. Data analysis indicates that both cosolutes significantly accelerate the rate of refolding to native or compact near-native conformations, but decrease the fraction of catalytically active enzyme recovered in the limit of long time. According to the simplest model that fits the data, both cosolutes accelerate a competing side reaction yielding inactive compact species. Acceleration of the side reaction by Ficoll is significantly greater than that of sucrose at equal w/v concentrations. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Monterroso, B (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM monterrosob@niddk.nih.gov RI Monterroso, Begona/J-9748-2014; OI Monterroso, Begona/0000-0003-2538-084X; Minton, Allen/0000-0001-8459-1247 FU Intramural NIH HHS NR 29 TC 12 Z9 12 U1 0 U2 2 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 NOV 16 PY 2007 VL 282 IS 46 BP 33452 EP 33458 DI 10.1074/jbc.M705157200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229XP UT WOS:000250840200025 PM 17878163 ER PT J AU Hanover, JA Love, DC DeAngelis, N O'Kane, ME Lima-Miranda, R Schulz, T Yen, YM Johnson, RC Prinz, WA AF Hanover, John A. Love, Dona C. DeAngelis, Nikki O'Kane, Meghan E. Lima-Miranda, Raquel Schulz, Timothy Yen, Yi-Meng Johnson, Reid C. Prinz, William A. TI The high mobility group box transcription factor Nhp6Ap enters the nucleus by a calmodulin-dependent, ran-independent pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PORE COMPLEX; SEX REVERSAL; PROTEIN IMPORT; TRANSPORT; BIOLOGY; SRY; RECOGNITION; INHIBITION; DOMAINS; SOX9 AB A gradient of Ran center dot GTP typically regulates traffic through the nuclear pore by modulating association of receptors with cargo. However, here we demonstrate that the yeast high mobility group box transcription factor Nhp6Ap enters the nucleus via a novel nuclear localization signal recognized by calcium calmodulin in a process that does not require Ran. Calmodulin is strictly required for the nondiffusional nuclear entry of Nhp6Ap. Calmodulin and DNA exhibit mutually exclusive binding to NHP6A, indicating that the directionality of Nhp6Ap nuclear accumulation may be driven by DNA-dependent dissociation of calmodulin. Our findings demonstrate that calmodulin can serve as a molecular switch triggering nuclear entry with subsequent dissociation of calmodulin binding upon interaction of cargo with chromatin. This pathway appears to be evolutionarily conserved; mammalian high mobility group box transcription factors often have two nuclear localization signals: one a classical Ran-dependent signal and a second that binds calmodulin. The finding that Nhp6Ap nuclear entry requires calmodulin but not Ran indicates that Nhp6Ap is a good model for studying this poorly understood but evolutionarily conserved calmodulin-dependent nuclear import pathway. C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Biol Chem, Sch Med, Los Angeles, CA 90095 USA. RP Prinz, WA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, 8 Ctr Dr,MSC 0851, Bethesda, MD 20892 USA. EM wprinz@helix.nih.gov FU Intramural NIH HHS NR 28 TC 22 Z9 22 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 NOV 16 PY 2007 VL 282 IS 46 BP 33743 EP 33751 DI 10.1074/jbc.M705875200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229XP UT WOS:000250840200056 PM 17878171 ER PT J AU Caposio, P Gugliesi, F Zannetti, C Sponza, S Mondini, M Medico, E Hiscott, J Young, HA Gribaudo, G Gariglio, M Landolfo, S AF Caposio, Patrizia Gugliesi, Francesca Zannetti, Claudia Sponza, Simone Mondini, Michele Medico, Enzo Hiscott, John Young, Howard A. Gribaudo, Giorgio Gariglio, Marisa Landolfo, Santo TI A novel role of the interferon-inducible protein IFI16 as inducer of proinflammatory molecules in endothelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; INTERCELLULAR-ADHESION MOLECULE-1; EPITHELIAL ICAM-1 EXPRESSION; GENE IFI16; INFLAMMATORY RESPONSE; TRANSCRIPTION FACTORS; HIN-200 FAMILY; DNA MICROARRAY; SYSTEMIC LUPUS; ACTIVATION AB The human IFI16 gene is an interferon-inducible gene implicated in the regulation of endothelial cell proliferation and tube morphogenesis. Immunohistochemical analysis has demonstrated that this gene is highly expressed in endothelial cells in addition to hematopoietic tissues. In this study, gene array analysis of human umbilical vein endothelial cells overexpressing IFI16 revealed an increased expression of genes involved in immunomodulation, cell growth, and apoptosis. Consistent with these observations, IFI16 triggered expression of adhesion molecules such as ICAM-1 and E-selectin or chemokines such as interleukin-8 or MCP-1. Treatment of cells with short hairpin RNA targeting IFI16 significantly inhibited ICAM-1 induction by interferon (IFN)-gamma demonstrating that IFI16 is required for proinflammatory gene stimulation. Moreover, functional analysis of the ICAM-1 promoter by deletion- or site-specific mutation demonstrated that NF-kappa B is the main mediator of IFI16-driven gene induction. NF-kappa B activation appears to be triggered by IFI16 through a novel mechanism involving suppression of I kappa B alpha mRNA and protein expression. Support for this finding comes from the observation that IFI16 targeting with specific short hairpin RNA down-regulates NF-kappa B binding activity to its cognate DNA and inhibits ICAM-1 expression induced by IFN-gamma. Using transient transfection and luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation, we demonstrate indeed that activation of the NF-kappa B response is mediated by IFI16-induced block of Sp1-like factor recruitment to the promoter of the I kappa B alpha gene, encoding the main NF-kappa B inhibitor. Activation of NF-kappa B accompanied by induction of proinflammatory molecules was also observed when I kappa B alpha expression was down-regulated by specific small interfering RNA, resulting in an outcome similar to that observed with IFI16 overexpression. Taken together, these data implicate IFI16 as a novel regulator of endothelial proinflammatory activity and provide new insights into the physiological functions of the IFN-inducible gene IFI16. C1 Univ Turin, Sch Med, Dept Publ Hlth & Microbiol, Lab Viral Pathogenesis, I-10126 Turin, Italy. Univ Turin, Inst Canc Res & Treatment, I-10126 Turin, Italy. McGill Univ, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada. NCI, Canc Res Ctr, Expt Immunol Lab, Natl Inst Hlth, Frederick, MD 21702 USA. Univ Piemonte Orientale, Dept Clin & Expt Med, I-28100 Novara, Italy. RP Landolfo, S (reprint author), Univ Turin, Sch Med, Dept Publ Hlth & Microbiol, Lab Viral Pathogenesis, Via Santena 9, I-10126 Turin, Italy. EM santo.landolfo@unito.it RI Young, Howard/A-6350-2008; Gribaudo, Giorgio/A-8872-2011; OI Young, Howard/0000-0002-3118-5111; Gribaudo, Giorgio/0000-0002-1583-9146; GUGLIESI, Francesca/0000-0001-6389-5129; Gariglio, Marisa/0000-0002-5187-0140 NR 47 TC 45 Z9 51 U1 2 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 NOV 16 PY 2007 VL 282 IS 46 AR 33515 DI 10.1074/jbc.M701846200 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229XP UT WOS:000250840200032 PM 17699163 ER PT J AU Macdonald, IM Brooks, BP Sieving, PA AF Macdonald, Ian M. Brooks, Brian P. Sieving, Paul A. TI Eyeing a new network SO SCIENCE LA English DT Letter C1 NEI, NIH, Bethesda, MD 20892 USA. RP Macdonald, IM (reprint author), NEI, NIH, Bethesda, MD 20892 USA. OI MacDonald, Ian/0000-0001-7472-8385 NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2007 VL 318 IS 5853 BP 1068 EP 1068 DI 10.1126/science.318.5853.1068 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 231OC UT WOS:000250957900019 PM 18006726 ER PT J AU Ludek, OR Marquez, VE AF Ludek, Olaf R. Marquez, Victor E. TI Convergent or linear? A challenging question in carbocyclic nucleoside chemistry SO SYNTHESIS-STUTTGART LA English DT Article DE medicinal chemistry; nucleosides; carbocycles; Mitsunobu reaction; regioselectivity ID POTENT ANTIVIRAL ACTIVITY; HERPES THYMIDINE KINASE; SIMPLEX-VIRUS TYPE-1; N-METHANOCARBATHYMIDINE; MITSUNOBU REACTION; ENANTIOSELECTIVE SYNTHESIS; N1-VERSUS O-2-ALKYLATION; BIOLOGICAL EVALUATION; ATOM ECONOMY; NEPLANOCIN-C AB North-methanocarbathymidine (N-MCT) is a carbocyclic nucleoside analogue with potent anti-HSV and KSHV activity. The critical step in the synthesis of N-MCT and other carbocyclic nucleoside analogues is the introduction of the nucleobase into the carbocyclic moiety. For this, convergent and linear strategies were compared side by side. In the convergent approach, the base was coupled to the carbocyclic moiety by either a Mitsunobu reaction or by displacement of a mesylate. This strategy leads to the formation of various amounts of the O-2-regioisomer, depending on the applied procedure. Additionally, by-products of the Mitsunobu reaction have to be separated from the coupling products. Although lengthier, the linear strategy leads selectively to the target compound N-MCT with overall yields comparable to the convergent approaches, making this strategy more compatible for future large-scale syntheses. C1 Natl Canc Inst, Ctr Canc Res, Med Chem Lab, Ft Detrick, MD 21702 USA. RP Marquez, VE (reprint author), Natl Canc Inst, Ctr Canc Res, Med Chem Lab, 376 Boyles St, Ft Detrick, MD 21702 USA. EM marquezv@mail.nih.gov NR 66 TC 7 Z9 7 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0039-7881 J9 SYNTHESIS-STUTTGART JI Synthesis PD NOV 16 PY 2007 IS 22 BP 3451 EP 3460 DI 10.1055/s-2007-990847 PG 10 WC Chemistry, Organic SC Chemistry GA 239GQ UT WOS:000251507200003 ER PT J AU Nakashima, E Tran, JR Welting, TJM Pruijn, GJM Hirose, Y Nishimura, G Ohashi, H Schurman, SH Cheng, J Candotti, F Nagaraja, R Ikegawa, S Schlessinger, D AF Nakashima, Eiji Tran, Joseph R. Welting, Tim J. M. Pruijn, Ger J. M. Hirose, Yuichiro Nishimura, Gen Ohashi, Hirofumi Schurman, Shepherd H. Cheng, Jun Candotti, Fabio Nagaraja, Ramaiah Ikegawa, Shiro Schlessinger, David TI Cartilage hair hypoplasia mutations that lead to RMRP promoter inefficiency or RNA transcript instability SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE cartilage hair hypoplasia; RMRP; mutation ID MRP RIBONUCLEOPROTEIN COMPLEX; SACCHAROMYCES-CEREVISIAE; JAPANESE PATIENTS; PROTEIN; GENE; MANIFESTATIONS; DYSPLASIA; SUBUNITS AB Cartilage hair hypoplasia (CHH; MIM 250250) is an autosomal recessive disease with diverse clinical manifestations. It is caused by mutations in RMRP gene, the RNA component of the ribonucleoprotein complex RNase MRP. Mutations in RMRP have been found in patients in the core promoter region or in the transcribed region, but the pathogenetic effect of the mutations is unclear. Real-time PCR assays confirmed that both promoter (c.-16_-1 dup and c.-15_+2 dup) and transcribed mutations (c.168G > A and c.218A > G) lower the expression level of RMRP. Experiments with 5'RACE, showed that the reduced transcription in the promoter mutants was accompanied by shifting of the transcription initiation sites to nucleotides 5'-upstream of the authentic site. Low levels of RMRP expression levels with transcript mutations were also seen when constructs encoding the wild-type and mutant genes were transfected into cultured cells. The reduced transcription was correlated with greater instability of mutant RMRP transcripts compared to controls. A comparable reduction was seen when a mouse gene containing the c.70A > G mutation (the major mutation in humans with CHH) was introduced into ES cells in place of one of the wild-type alleles. The low expression level of the c.70A > G Rmrp RNA was confirmed by expression assays into cultured cells, and was again correlated with RNA instability. Our results indicate that a loss of mutant RNA transcripts is a critical feature of pathogenesis. (C) 2007 Wiley-Liss, Inc. C1 RIKEN, Lab Bone & Joint Dis, SNP Res Ctr, Minato Ku, Tokyo 1088639, Japan. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Radboud Univ Nijmegen, Inst Mol & Mat, Nijmegen Ctr Mol Life Sci, Dept Biomol Chem, Nijmegen, Netherlands. Tokyo Metropolitan Kiyose Childrens Hosp, Dept Radiol, Kiyose, Japan. Saitama Childrens Med Ctr, Div Med Genet, Iwatsuki, Saitama, Japan. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Schlessinger, D (reprint author), RIKEN, Lab Bone & Joint Dis, SNP Res Ctr, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. EM schlessingerd@grc.nia.nih.gov RI Pruijn, Ger/D-6664-2012; Ikegawa, Shiro/N-6895-2015; OI Ikegawa, Shiro/0000-0003-0316-2147; Schurman, Shepherd/0000-0002-9133-7906 FU Intramural NIH HHS NR 25 TC 17 Z9 17 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV 15 PY 2007 VL 143A IS 22 BP 2675 EP 2681 DI 10.1002/ajmg.a.32053 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 228EA UT WOS:000250708900007 PM 17937437 ER PT J AU Solomon, BD Turner, CE Klugman, D Sparks, SE AF Solomon, Benjamin D. Turner, Clesson E. Klugman, Darren Sparks, Susan E. TI Trisomy 9 mosaicism and XX sex reversal SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE trisomy; sex reversal; chromosome 9 ID STEROIDOGENIC FACTOR-1; DISTAL 9P; FEMALES; REGION; MEDAKA; DMRT1; GENES; GIRL; MICE; CGH AB We report on a case of a phenotypic male infant who was referred to the genetics service due to dysmorphic features and congenital cardiac anomalies. Dysmorphic features included low-set, posteriorly rotated ears with squared, simple helices, midface hypoplasia, a broad nasal root with wide nasal alae, small mouth, micrognathia, short neck; overlapping fingers, rocker-bottom feet, prominent heels, and hypoplastic toenails. The phallus was normal and no testes were palpable in the scrotal sac. Cardiac anomalies included tricuspid atresia and a ventricular septal defect. The karyotype was 46,XX. Diagnostic microarray demonstrated evidence for trisomy 9 mosaicism, metaphase FISH revealed trisomy 9 on 7% of cultured cells, and interphase FISH analysis of a peripheral blood smear showed trisomy 9 in 78% of the cells examined. This is the first reported case of XX sex reversal in a patient with trisomy 9 mosaicism. (C) 2007 Wiley-Liss, Inc. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Crit Care & Cardiol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Genet & Metab, Washington, DC 20010 USA. RP Solomon, BD (reprint author), NHGRI, NIH, Bldg 10,3C-710, Bethesda, MD 20892 USA. EM bsolomon@cnmc.org NR 24 TC 4 Z9 4 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV 15 PY 2007 VL 143A IS 22 BP 2688 EP 2691 DI 10.1002/ajmg.a.31996 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 228EA UT WOS:000250708900009 PM 17935231 ER PT J AU Stewart, DR Kleefstra, T AF Stewart, Douglas R. Kleefstra, Tjitske TI The chromosome 9q subtelomere deletion syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE chromosome 9q; subtelomere deletion; microdeletion; EHMT1; histone methylation ID MENTAL-RETARDATION; GENOTYPE-PHENOTYPE; TERMINAL DELETION; REARRANGEMENTS; 9Q34.3; DUPLICATION; CHILDREN; FEATURES; (9)(Q34.3); PATIENT AB The chromosome 9q subtelomere deletion syndrome (9qSTDS) is among the first and most common clinically recognizable syndromes to arise from widespread testing by fluorescent in situ hybridization (FISH) of subtelomere deletions. There are about 50 reported cases worldwide. Affected individuals invariably have severe hypotonia with speech and gross motor delay. The facial gestalt is distinct and features absolute or relative microor brachycephaly, hypertelorism, synophrys, and/or arched eyebrows, mid-face hypoplasia, a short nose with upturned nares, a protruding tongue with everted lower lip and down-turned corners of the mouth. Approximately half of affected individuals have congenital heart defects (primarily ASD or VSD). A significant minority have epilepsy and/or behavioral and sleep disturbances. A variety of other major and minor eye, ear, genital, and limb anomalies have been reported. Most patients have sub-microscopic deletions of the subtelomere region of chromosome 9q34.3 that range from <400 kb to >3 Mb. The 9qSTDS is caused by haploinsufficiency of EHMT1, a gene whose protein product (Eu-HMTase1) is a histone H3 Lys 9 (H3-K9) methyltransferase. This was established by identification of three patients with features of the syndrome and either mutations or a balanced translocation in EHMT1. H3-K9 histone methylation is restricted to the euchromatin of mammals and functions to silence individual genes. Deletion size does not correlate with the severity of the 9qSTDS since patients with mutations in EHMT1 are as severely affected as those with submicroscopic deletions. Patients clinically suspected of having the 9qSTDS but with normal subtelomere deletion testing by FISH or MLPA should be considered for detailed 9q MLPA analysis and/or sequencing of EHMT1. EHMT1 is another example in the growing list: of genes responsible for brain development that appear to play a role in chromatin remodeling. Published 2007 Wiley-Liss, Inc. C1 Natl Inst Hlth, Bethesda, MD USA. Radbound Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands. RP Stewart, DR (reprint author), NHGRI, NIH, 49 Convent Dr,Bldg 49,Room 4A62, Bethesda, MD 20892 USA. EM drstewart@mail.nih.gov FU Intramural NIH HHS NR 27 TC 47 Z9 52 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD NOV 15 PY 2007 VL 145C IS 4 BP 383 EP 392 DI 10.1002/ajmg.c.30148 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 235JP UT WOS:000251230300008 PM 17910072 ER PT J AU de Gonzalez, AB Kim, KP Samet, JM AF de Gonzalez, Amy Berrington Kim, Kwang Pyo Samet, Jonathan M. TI Radiation-induced cancer risk from annual computed tomography for patients with cystic fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE computed tomography; cancer; radiation; cystic fibrosis; risk ID POOLED ANALYSIS; BREAST; CT AB Rationale. Computed tomography (CT) is being considered as a tool for routine monitoring of lung damage in people with cystic fibrosis. Concern has been raised, however, about the associated risk of radiation-induced cancer. Objectives: To estimate the risk of radiation-induced cancer from lung CT for patients with cystic fibrosis, assuming annual monitoring starting at age 2 years. Methods: Radiation risk models (derived primarily from the study of Japanese atomic bomb survivors) were used to estimate the excess risk of radiation-induced cancer for the organs that receive measurable doses from lung CT. Two scenarios were considered: median survival to age 36 years (approximate current median survival) and median survival to age 50 years (projected median survival by 2030). Measurements and Main Results: The estimated risk of radiation-induced cancer from annual lung CT was 0.02% for males and 0.07% for females assuming median survival to age 36 years. The estimated risks increased to 0.08% for males and 0.46% for females assuming median survival increases to age 50 years. The risks are higher for females because of the risk of radiation-induced breast cancer (50% of total risk) and higher risk of thyroid cancer. Conclusions: The cumulative risk of radiation-induced cancer from repeated lung CT scans for patients with cystic fibrosis is relatively small (less than 0.5%). However, routine monitoring should not be recommended until there is a demonstrated benefit that will outweigh these risks. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD USA. RP de Gonzalez, AB (reprint author), 615 N Wolfe St, Baltimore, MD 21205 USA. EM aberring@jhsph.edu NR 16 TC 34 Z9 34 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2007 VL 176 IS 10 BP 970 EP 973 DI 10.1164/rccm.200704-591OC PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230PW UT WOS:000250889400005 PM 17717201 ER PT J AU Grillon, C Avenevoli, S Daurignac, E Merikangas, KR AF Grillon, Christian Avenevoli, Shelli Daurignac, Elsa Merikangas, Kathleen R. TI Fear-potentiated startle to threat, and prepulse inhibition among young adult nonsmokers, abstinent smokers, and nonabstinent smokers SO BIOLOGICAL PSYCHIATRY LA English DT Article DE affective; anxiety; fear-potentiated startle; nicotine; prepulse inhibition; smoking ID CIGARETTE-SMOKING; NICOTINE DEPENDENCE; ACOUSTIC STARTLE; ANXIETY DISORDERS; REFLEX; RESPONSES; STRESS; STATES; MODULATION; WITHDRAWAL AB Background: Evidence suggests that the transition from experimental to regular smoking is facilitated by the influence of tobacco on affective and attentional mechanisms. The objective of this study was to examine affective and attentional responses in young adult smokers using fear-potentiated startle and prepulse inhibition. Methods: Participants were 56 college nonsmokers, nonabstinent smokers, and overnight-abstinent smokers. The fear-potentiated startle test examined phasic responses to imminent threat cues and more sustained responses to unpredictable aversive events. Prepulse inhibition investigated responses to attended and ignored prepulse stimuli. Results: Abstinent and nonabstinent smokers showed increased sustained potentiation of startle to contextual cues, compared to controls. Abstinent smokers showed increased fear-potentiated startle to threat cues, compared to nonsmokers. PPI did not discriminate between abstinent or nonabstinent smokers and controls. Conclusions: These findings suggest that negative affectivity or anxiety is associated with smoking, particularly during short withdrawal. Potentiated startle may provide a valuable tool in understanding the biologic mechanisms underlying nicotine withdrawal and inform cessation and prevention efforts. C1 NIH, NIMH, Dept Human & Hlth Serv, Unit Affect Psychophysiol, Bethesda, MD 20892 USA. NIH, NIMH, Dept Human & Hlth Serv, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. NIH, NIMH, Dept Human & Hlth Serv, Intramural Res Program, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Psychiat, Buffalo, NY 14260 USA. RP Grillon, C (reprint author), 15K N Dr,Bldg 15K,Room 113,MSC 2670, Bethesda, MD 20892 USA. EM christian.grillon@nih.gov FU Intramural NIH HHS [Z01 MH002798-06] NR 43 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2007 VL 62 IS 10 BP 1155 EP 1161 DI 10.1016/j.biopsych.2006.12.027 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 230WB UT WOS:000250905800013 PM 17543892 ER PT J AU Grillon, C Duncko, R Covington, MF Kopperman, L Kling, MA AF Grillon, Christian Duncko, Roman Covington, Matthew F. Kopperman, Lori Kling, Mitchel A. TI Acute stress potentiates anxiety in humans SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anxiety; cortisol; fear-potentiated startle; stress ID STRIA TERMINALIS; BED NUCLEUS; PARAVENTRICULAR NUCLEUS; RESTRAINT STRESS; STARTLE REFLEX; MESSENGER-RNA; HEALTHY-MEN; FEAR; RESPONSES; EXPOSURE AB Background: Stress is an important factor in the development and maintenance of anxiety disorders. Stress also potentiates anxiety-like response in animals, but empirical evidence for a similar effect in humans is still lacking. Methods: To test whether stress increases anxiety in humans, we examined the ability of a social stressor (speech and a counting task) to potentiate the facilitation of startle in the dark. Measures of subjective distress and of hypothalamic-pituitary-adrenal axis and autonomic nervous system activity (e.g., salivary cortisol, alpha-amylase, blood pressure, and heart rate) were also taken to confirm the effectiveness of the stress manipulation. Results: Startle was significantly facilitated in the dark. This effect was potentiated by prior exposure to the social stressor. The social stressor induced increases in salivary cortisol and alpha amylase as well as increases in blood pressure, heart rate, and subjective distress. Conclusion: The findings indicate that stress potentiates anxiety. Animal studies suggest that such an effect might be mediated by glucocorticoid effects on corticotropin-releasing hormone in limbic structures. C1 NIMH, MAP, Unit Affect Psychophysiol, Natl Inst Hlth, Bethesda, MD 20892 USA. NIMH, MAP, Sect Dev Genet Epidemiol, Natl Inst Hlth, Bethesda, MD 20892 USA. NIMH, MAP, Intramural Res Program, Natl Inst Hlth, Bethesda, MD 20892 USA. NIMH, MAP, Mood & Anxiety Disorder Program, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Grillon, C (reprint author), NIMH, MAP, Unit Affect Psychophysiol, Natl Inst Hlth, 15K N Dr,Bldg 15K,Room 113,MSC 2670, Bethesda, MD 20892 USA. EM Christian.grillon@nih.gov RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 FU Intramural NIH HHS [Z01 MH002798-06] NR 27 TC 35 Z9 35 U1 0 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 NOV 15 PY 2007 VL 62 IS 10 BP 1183 EP 1186 DI 10.1016/j.biopsych.2007.06.007 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 230WB UT WOS:000250905800018 PM 17692829 ER PT J AU Salvadori, S Trapella, C Fiorini, S Negri, L Lattanzi, R Bryant, SD Jinsmaa, Y Lazarus, LH Balboni, G AF Salvadori, Severo Trapella, Claudio Fiorini, Stella Negri, Lucia Lattanzi, Roberta Bryant, Sharon D. Jinsmaa, Yunden Lazarus, Lawrence H. Balboni, Gianfranco TI A new opioid designed multiple ligand derived from the mu opioid agonist endomorphin-2 and the delta opioid antagonist pharmacophore Dmt-Tic SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE designed multiple ligand; endomorphin-2; Dmt-Tic pharmacophore; analgesia; physical dependence; opioid peptides; delta opioid receptors; mu opioid receptors ID MEDIATED ANALGESIA; RECEPTOR AGONISTS; OPIATE RECEPTOR; HIGH-AFFINITY; POTENT; ANALOGS; SELECTIVITY; MICE; PEPTIDES; MORPHINE AB Opioid compounds with mixed mu agonist/delta antagonist properties could be used as analgesics with low propensity to induce tolerance and dependence. Here we report the synthesis of a new designed multiple ligand deriving from the p selective agonist endomorphin-2 and the delta selective antagonist pharmacophore Dmt-Tic. As predicted, the resulting bivalent ligand showed a p agonist/delta antagonist profile deriving fi-om the corresponding activities of each pharmacophore. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Ferrara, Ctr Biotechnol, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, I-00185 Rome, Italy. NIEHS, Lab Pharmacol & Chem, Med Chem Grp, Res Triangle Pk, NC 27709 USA. Univ Cagliari, Dept Toxicol, I-09126 Cagliari, Italy. RP Balboni, G (reprint author), Univ Ferrara, Ctr Biotechnol, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. EM gbalboni@unica.it RI Trapella, Claudio/I-2128-2012; OI Trapella, Claudio/0000-0002-6666-143X; LATTANZI, Roberta/0000-0002-6377-9256; SALVADORI, Severo/0000-0002-8224-2358 FU Intramural NIH HHS [Z01 ES090053-20] NR 36 TC 20 Z9 21 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD NOV 15 PY 2007 VL 15 IS 22 BP 6876 EP 6881 DI 10.1016/j.bmc.2007.08.047 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 222VG UT WOS:000250324900002 PM 17851080 ER PT J AU Chong, HS Mhaske, S Lin, M Bhuniya, S Song, HA Brechbiel, MW Sun, XK AF Chong, Hyun-Soon Mhaske, Santosh Lin, Mai Bhuniya, Sankar Song, Hyun A. Brechbiel, Martin W. Sun, Xiankai TI Novel synthetic ligands for targeted PET imaging and radiotherapy of copper SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE synthetic chelates; macrocyclic ligands; Cu-64; PET imaging; targeted radiotherapy; serum stability ID IN-VITRO; RADIOIMMUNOTHERAPY AB Novel ligands, NBEA, NBPA, NETA, NE3TA, and NE3TA-Bn, were synthesized and evaluated as potential chelators of copper radioisotopes for use in targeted positron emission tomography (PET) imaging or radiation therapy. The new ligands were radiolabeled with Cu-64, and in vitro stability of the radiolabeled complexes was assessed in rat serum. Serum stability results suggest that among the ligands tested, NETA, NE3TA, and NE3TA-Bn form stable complexes with Cu-64. (C) 2007 Elsevier Ltd. All rights reserved. C1 IIT, Dept Chem Biol & Phys Sci, Chem Div, Chicago, IL 60616 USA. Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. NIH, Natl Canc Inst, Ctr Canc Res, Radioimmun & Inorgan Chem Sect,Radiol Oncol Branc, Bethesda, MD USA. RP Chong, HS (reprint author), IIT, Dept Chem Biol & Phys Sci, Chem Div, 3101 S Dearborn St,LS 182, Chicago, IL 60616 USA. EM Chong@iit.edu OI Bhuniya, Sankarprasad /0000-0001-5080-0936 FU Intramural NIH HHS [Z01 SC006353-24]; NCI NIH HHS [R01 CA112503-01A2, R01 CA112503] NR 8 TC 23 Z9 23 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 15 PY 2007 VL 17 IS 22 BP 6107 EP 6110 DI 10.1016/j.bmc1.2007.09.052 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 230WF UT WOS:000250906200011 PM 17911020 ER PT J AU Holden, KG Tidgewell, K Marquam, A Rothman, RB Navarro, H Prisinzano, TE AF Holden, Kenneth G. Tidgewell, Kevin Marquam, Alfred Rothman, Richard B. Navarro, Hernan Prisinzano, Thomas E. TI Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Exploration of the 1-position SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE kappa; salvinorin A; Salvia divinorum; opioid; antagonist ID MU-OPIOID RECEPTOR; SALVINORIN-A ANALOGS; G-PROTEIN; SALVINICIN-B; ACTIVATION; AGONIST; LIGANDS; ANALGESICS; EFFICACY; DENSITY AB Modification of the C-1 ketone of salvinorin A (2a) produces analogues with opioid antagonist properties. Of particular significance is the finding that 1-deoxo-1,10-dehydrosalvinorin A (11a) is a moderately potent antagonist at all three opioid receptor subtypes, and that herkinorin (2b), a mu agonist, is converted to a weak antagonist by removal of the C-1 ketone (3b and 11b). These observations suggest that the ketone of 2b is a key structural feature responsible for p agonist activity. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. Holden Lab, Carmel Valley, CA 93923 USA. NIDA, IRP, NIH, DHHS,Clin Pharmacol Sect, Baltimore, MD 21224 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Prisinzano, TE (reprint author), Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. EM prisinza@ku.edu RI Prisinzano, Thomas/B-7877-2010; OI Tidgewell , Kevin/0000-0002-0501-2604 FU NIDA NIH HHS [DA 018151, R01 DA018151, R01 DA018151-01A2]; NIGMS NIH HHS [T32 GM067795] NR 28 TC 18 Z9 18 U1 0 U2 5 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 NOV 15 PY 2007 VL 17 IS 22 BP 6111 EP 6115 DI 10.1016/j.bmc1.2007.09.050 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 230WF UT WOS:000250906200012 PM 17904842 ER PT J AU Seam, P Juweid, ME Cheson, BD AF Seam, Pamela Juweid, Malik E. Cheson, Bruce D. TI The role of FDG-PET scans in patients with lymphoma SO BLOOD LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; NON-HODGKINS-LYMPHOMA; STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; COLONY-STIMULATING FACTOR; WHOLE-BODY; MALIGNANT-LYMPHOMA; FOLLOW-UP; COMPUTED-TOMOGRAPHY; F-18 FLUORODEOXYGLUCOSE AB 18-Fluoro-deoxyglucose positron emission tomography (FDG-PET) is a noninvasive, 3-dimensional imaging modality that has become widely used in the management of patients with malignant lymphomas. This technology has been demonstrated to be more sensitive and specific than either (67)gallium scintigraphy or computerized tomography, providing a more accurate distinction between scar or fibrosis and active tumor. PET scans have been evaluated in pretreatment staging, restaging, monitoring during therapy, posttherapy surveillance, assessment of transformation, and, more recently, as a surrogate marker in new drug development. Data to support these various roles require prospective validation. Moreover, caution must be exercised in the interpretation of PET scans because of technical limitations, variability of FDG avidity among the different lymphoma histologic subtypes, and in the large number of etiologies of false-negative and falsepositive results. Recent attempts to standardize PET in clinical trials and incorporation of this technology into uniformly adopted response criteria will hopefully lead to improved outcome for patients with lymphoma. C1 Natl Canc Inst, Bethesda, MD 20892 USA. Univ Iowa, Dept Radiol, Iowa City, IA USA. Georgetown Univ Hosp, Div Hematol, Div Oncol, Washington, DC USA. RP Cheson, BD (reprint author), Natl Canc Inst, Bethesda, MD 20892 USA. EM bdc4@georgetown.edu NR 99 TC 161 Z9 170 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2007 VL 110 IS 10 BP 3507 EP 3516 DI 10.1182/blood-2007-06-097238 PG 10 WC Hematology SC Hematology GA 231KS UT WOS:000250946300012 PM 17709603 ER PT J AU Klion, AD Robyn, J Maric, I Fu, W Schmid, L Lemery, S Noel, P Law, MA Hartsell, M Talar-Williams, C Fay, MP Dunbar, CE Nutman, TB AF Klion, Amy D. Robyn, Jamie Maric, Irina Fu, Weiming Schmid, Laura Lemery, Steven Noel, Pierre Law, Melissa A. Hartsell, Marilyn Talar-Williams, Cheryl Fay, Michael P. Dunbar, Cynthia E. Nutman, Thomas B. TI Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia: implications for optimal dosing SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; COMPLETE CYTOGENETIC REMISSION; COMPLETE MOLECULAR REMISSION; HYPEREOSINOPHILIC SYNDROME; PROGENITORS; INTERFERON; MUTATIONS; RESPONSES; REVERSAL AB Although imatinib is clearly the treatment of choice for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia (CEL), little is known about optimal dosing, duration of treatment, and the possibility of cure in this disorder. To address these questions, 5 patients with F1P1L1/PDGFRA-positive CEL with documented clinical, hematologic, and molecular remission on imatinib (400 ring daily) and without evidence of cardiac involvement were enrolled in a dose de-escalation trial. The imatinib dose was tapered slowly with close follow-up for evidence of clinical, hematologic, and molecular relapse. Two patients with endomyocardial fibrosis were maintained on imatinib 300 to 400 mg daily and served as controls. All 5 patients who underwent dose de-escalation, but neither of the control patients, experienced molecular relapse (P <.05). None developed recurrent symptoms, and eosinophil counts, serum B12, and tryptase levels remained suppressed. Reinitiation of therapy at the prior effective dose led to molecular remission in all 5 patients, although 2 patients subsequently required increased dosing to maintain remission. These data are consistent with suppression rather than elimination of the clonal population in FIP1L1/PDGFRA-positive CEL and suggest that molecular monitoring may be the most useful method in determining optimal dosing without the risk of disease exacerbation. This trial was registered at http://www.clinical trials.gov as no. NCT00044304. C1 NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD USA. NIAID, Lab Allerg Dis, Bethesda, MD USA. Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD USA. NIH, NIAID, Biostat Res, Bethesda, MD USA. RP Klion, AD (reprint author), NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. EM aklion@nih.gov RI Fay, Michael/A-2974-2008; OI Klion, Amy/0000-0002-4986-5326; Fay, Michael P./0000-0002-8643-9625 FU Intramural NIH HHS NR 20 TC 57 Z9 64 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2007 VL 110 IS 10 BP 3552 EP 3556 DI 10.1182/blood-2007-07-100164 PG 5 WC Hematology SC Hematology GA 231KS UT WOS:000250946300018 PM 17709602 ER PT J AU Jorritsma, A Gomez-Eerland, R Dokter, M van de Kasteele, W Zoet, YM Doxiadis, IIN Rufer, N Romero, P Morgan, RA Schumacher, TNM Haanen, JBAG AF Jorritsma, Annelies Gomez-Eerland, Raquel Dokter, Maarten van de Kasteele, Willeke Zoet, Yvonne M. Doxiadis, Ilias I. N. Rufer, Nathalie Romero, Pedro Morgan, Richard A. Schumacher, Ton N. M. Haanen, John B. A. G. TI Selecting highly affine and well-expressed TCRs for gene therapy of melanoma SO BLOOD LA English DT Article ID HUMAN T-LYMPHOCYTES; GRAFT-VERSUS-LEUKEMIA; CELL TRANSFER THERAPY; CANCER REGRESSION; TUMOR-ANTIGEN; CLASS-I; TRANSGENE EXPRESSION; ADOPTIVE TRANSFER; REACTIVE TCR; SINGLE-CHAIN AB A recent phase I trial has demonstrated that the generation of tumor-reactive T lymphocytes by transfer of specific T-cell receptor (TCR) genes into autologous lymphocytes is feasible. However, compared with results obtained by infusion of tumor-infiltrating lymphocytes, the response rate observed in this first TCR gene therapy trial is low. One strategy that is likely to enhance the success rate of TCR gene therapy is the use of tumor-reactive TCRs with a higher capacity for tumor cell recognition. We therefore sought to develop standardized procedures for the selection of well-expressed, high-affinity, and safe human TCRs. Here we show that TCR surface expression can be improved by modification of TCR alpha and beta sequences and that such improvement has a marked effect on the in vivo function of TCR gene-modified T cells. From a panel of human, melanoma-reactive TCRs we subsequently selected the TCR with the highest affinity. Furthermore, a generally applicable assay was used to assess the lack of alloreactivity of this TCR against a large series of common human leukocyte antigen alleles. The procedures described in this study should be of general value for the selection of well- and stably expressed, high-affinity, and safe human TCRs for subsequent clinical testing. C1 Netherlands Canc Inst, Dept Immunol, Amsterdam, Netherlands. Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands. Ludwig Inst Canc Res, Div Clin Onco Immunol, Lausanne, Switzerland. NIH, Natl Canc Inst, Surg Branch, Bethesda, MD 20892 USA. RP Haanen, JBAG (reprint author), Netherlands Canc Inst, Dept Immunol, Plesmanlaan 121, Amsterdam, Netherlands. EM j.haanen@nki.nl NR 50 TC 60 Z9 62 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2007 VL 110 IS 10 BP 3564 EP 3572 DI 10.1182/blood-2007-02-075010 PG 9 WC Hematology SC Hematology GA 231KS UT WOS:000250946300021 PM 17660381 ER PT J AU Espey, DK Wu, XC Swan, J Wiggins, C Jim, MA Ward, E Wingo, PA Howe, HL Ries, LAG Miller, BA Jemal, A Ahmed, F Cobb, N Kaur, JS Edwards, BK AF Espey, David K. Wu, Xiao-Cheng Swan, Judith Wiggins, Charles Jim, Melissa A. Ward, Elizabeth Wingo, Phyllis A. Howe, Holly L. Ries, Lynn A. G. Miller, Barry A. Jemal, Ahmedin Ahmed, Faruque Cobb, Nathaniel Kaur, Judith S. Edwards, Brenda K. TI Annual report to the nation on the status of cancer, 1975-2004, featuring cancer in American Indians and Alaska natives SO CANCER LA English DT Editorial Material DE cancer; incidence; mortality; American Indian; Alaska native; National Program of Cancer Registries; surveillance; epidemiology; and end results; American Cancer Society; North American Association of Central Cancer Registries; US; health disparity ID ADVANCED PROSTATE-CANCER; RENAL-CELL CARCINOMA; UNITED-STATES; COLORECTAL-CANCER; NEW-MEXICO; LUNG-CANCER; HELICOBACTER-PYLORI; CIGARETTE-SMOKING; GASTRIC-CANCER; INTERNATIONAL TRENDS AB BACKGROUND. The American Cancer Society; the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate annually to provide updated information on cancer occurrence and trends in the U.S. The 2007 report features a comprehensive compilation of cancer information for American Indians and Alaska Natives (AI/AN). METHODS. Cancer incidence data were available for up to 82% of the U.S. population. Cancer deaths were available for the entire U.S. population. Long-term (1975 through 2004) and fixed-interval (1995 through 2004) incidence and mortality trends were evaluated by annual percent change using regression analyses (2-sided P < .05). Cancer screening, risk factors, socioeconomic characteristics, incidence data, and stage were compiled for non-Hispanic whites (NHW) and AI/AN across 6 regions of the U.S. RESULTS. Overall cancer death rates decreased by 2.1% per year from 2002 through 2004, nearly twice the annual decrease of 1.1% per year from 1993 through 2002. Among men and women, death rates declined for most cancers. Among women, lung cancer incidence rates no longer were increasing and death rates, although they still were increasing slightly, were increasing at a much slower rate than in the past. Breast cancer incidence rates in women decreased 3.5% per year from 2001 to 2004, the first decrease observed in 20 years. Colorectal cancer incidence and death rates and prostate cancer death rates declined, with colorectal cancer death rates dropping more sharply from 2002 through 2004. Overall, rates for AI/AN were lower than for NHW from 1999 through 2004 for most cancers, but they were higher for cancers of the stomach, liver, cervix, kidney, and gallbladder. Regional analyses, however, revealed high rates for AI/AN in the Northern and Southern Plains and Alaska. For cancers of the breast, colon and rectum, prostate, and cervix, AI/AN were less likely than NHW to be diagnosed at localized stages. CONCLUSIONS. For all races/ethnicities combined in the U.S., favorable trends in incidence and mortality were noted for lung and colorectal cancer in men and women and for breast cancer in women. For the AI/AN population, lower overall cancer incidence and death rates obscured important variations by geographic regions and less favorable healthcare access and socioeconomic status. Enhanced tobacco control and cancer screening, especially in the Northern and Southern Plains and Alaska, emerged as clear priorities. C1 Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA USA. N Amer Assoc Cent Canc Registries, Springfield, IL USA. Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, Program Epidemiol,Louisiana Tumor Reg, New Orleans, LA USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ New Mexico, New Mexico Tumor Reg, Albuquerque, NM 87131 USA. Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. Indian Hlth Serv, Div Epidemiol & Dis Prevent, Albuquerque, NM USA. Mayo Clin, Coll Med, Dept Oncol, Rochester, MN USA. RP Espey, DK (reprint author), Indian Hlth Serv, Ctr Dis Prevent & Control, Div Epidemiol & Dis Prevent, Div Canc Prevent & Control, 5300 Homestead NE, Albuquerque, NM 87110 USA. EM david.espey@ihs.gov NR 165 TC 314 Z9 320 U1 4 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2007 VL 110 IS 10 BP 2119 EP 2152 DI 10.1002/cncr.23044 PG 34 WC Oncology SC Oncology GA 230XZ UT WOS:000250911000001 PM 17939129 ER PT J AU Byun, HM Wong, HL Birnstein, EA Wolff, EM Liang, G Yang, AS AF Byun, Hyang-Min Wong, Hui-Lee Birnstein, Elliott Aaron Wolff, Erika M. Liang, Gangning Yang, Allen S. TI Examination of IGF2 and H19 loss of imprinting in bladder cancer SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-II; CTCF-BINDING SITES; COLORECTAL-CANCER; WILMS-TUMOR; GENE; METHYLATION; EXPRESSION; PROMOTER; HYPOMETHYLATION; HETEROZYGOSITY AB Loss of imprinting (1,01) is a common epigenetic event in cancer and may serve as an early biomarker in some cancers. To obtain a better understanding of 1,01, we studied 41 bladder tumors and their adjacent normal bladder mucosa. We found 2/9 (22.2%) cases that displayed LOI of IGF2 and 2/16 (12.5%) that had LOI of H19, as determined by the evaluation of mRNA for biallelic expression. In addition, we examined allele-specific methylation of the differentially methylated regions (DMR) of IGF2 and H19 using a new allele-specific pyrosequencing assay. We found that DNA methylation changes were a common finding (21/30, 70%) in the DMR regions, but could not clearly link DNA methylation changes with LOI as measured by biallelic expression. LOI and allele-specific DNA methylation changes are present in bladder cancer; however, a better understanding of the biology of LOI and its relationship to DNA methylation changes is needed before its use as an epigenetic biomarker. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Div Hematol, Los Angeles, CA 90033 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biochem, Los Angeles, CA 90033 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Yang, AS (reprint author), Univ So Calif, USC Norris Canc Ctr, 1441 Eastlake Ave,Room 6428, Los Angeles, CA 90033 USA. EM allenyan@usc.edu OI Liang, Gangning/0000-0001-8664-922X; Byun, Hyang-Min/0000-0002-6278-3165 FU NCI NIH HHS [CA 86871-01A2] NR 32 TC 67 Z9 69 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2007 VL 67 IS 22 BP 10753 EP 10758 DI 10.1158/0008-5472.CAN-07-0329 PG 6 WC Oncology SC Oncology GA 232UA UT WOS:000251044000018 PM 18006818 ER PT J AU Yamashita, T Budhu, A Forgues, M Wang, XW AF Yamashita, Taro Budhu, Anturadha Forgues, Marshorma Wang, Xin Wei TI Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma SO CANCER RESEARCH LA English DT Article ID VIRUS-X PROTEIN; EP-CAM; MOLECULAR PATHOGENESIS; GENETIC ALTERATIONS; PROGENITOR CELLS; BREAST-CANCER; LUNG-CANCER; EXPRESSION; LIVER; MUTATIONS AB The heterogeneous nature of hepatocellular carcinoma (HCC) and the lack of appropriate biomarkers have hampered patient prognosis and treatment stratification. Using a gene expression profiling approach, we recently identified a novel prognostic HCC subtype that resembles hepatic progenitor cells with the activation of stem cell markers and Wnt-beta-catenin signaling, based on EpCAM (epithelial cell adhesion molecule, a hepatic stem cell marker) expression. In this study, we investigated whether the activation of the Wnt-beta-catenin pathway regulates EpCAM expression. We found that nuclear accumulation of beta-catenin induced, whereas the degradation of beta-catenin or inhibition of Tcf/beta-catenin complex formation reduced EpCAM gene expression in cultured normal human hepatocytes and HCC cell lines. We identified two Tcf binding elements in the EpCAM promoter that specifically bound to Tcf-4 in an electrophoretic mobility shift assay. EpCAM promoter luciferase activity was down-regulated by the degradation of beta-catenin or inhibition of Tcf/beta-catenin complex formation. Furthermore, we found that EpCAM-positive HCC is much more sensitive to Tcf/beta-catenin binding inhibitors than EpCAM-negative HCC in vitro. Taken together, our data indicate that EpCAM is a Wnt-beta-catenin signaling target gene and may be used to facilitate HCC prognosis by enabling effective stratification of patients with predicted pharmacologic responses to Wnt-beta-catenin signaling antagonists. C1 NCI, Ctr Canc Res, Human Carcinogenesis Lab, Liver Carcinogenesis Sect, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Ctr Canc Res, Human Carcinogenesis Lab, Liver Carcinogenesis Sect, 37 Convent Dr,Room 3044A,MSC 4258, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009 FU Intramural NIH HHS NR 49 TC 209 Z9 221 U1 2 U2 19 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2007 VL 67 IS 22 BP 10831 EP 10839 DI 10.1158/0008-5472.CAN-07-0908 PG 9 WC Oncology SC Oncology GA 232UA UT WOS:000251044000028 PM 18006828 ER PT J AU McIlhatton, NA Tyler, J Burkholder, S Ruschoff, J Rigas, B Kopelovich, L Fishel, R AF McIlhatton, Nfichael A. Tyler, Jessica Burkholder, Susan Ruschoff, Josef Rigas, Basil Kopelovich, Levy Fishel, Richard TI Nitric oxide-donating aspirin derivatives suppress Microsatellite instability in mismatch repair-deficient and hereditary nonpolyposis colorectal cancer cells SO CANCER RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLON-CANCER; LYNCH-SYNDROME; MUTATOR PHENOTYPE; PREVENTION; GROWTH; NSAIDS; GENES; CYCLOOXYGENASE-2; CARCINOGENESIS AB Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are an emergent class of pharmaceutical derivatives with promising utility as cancer chemopreventive agents. Aspirin and sulindac have been shown to be effective in selecting for cells with reduced microsatellite instability (MSI) that is inherent in mismatch repair (MMR)-deficient hereditary nonpolyposis colorectal cancer (HNPCC cells. The effect of NO-NSAIDs on MSI in MMA-deficient HNPCC cells is unknown. Here, we have examined genetically defined MMR-deficient murine embryo fibroblasts, murine colonocytes, and isogenic human HNPCC tumor cell lines treated with acetylsalicylic acid (aspirin; ASA) and three isomeric derivatives of NO-aspirin (NO-ASA). The MSI profiles were determined and compared with the Bethesda Criteria. We found that the ASA- and NO-ASA-treated MMR-deficient cell lines displayed a dose-dependent suppression of MSI that appeared as early as 8 weeks and gradually increased to include up to 67% of the microsatellite sequences examined after 19 to 20 weeks of continuous treatment. Residual resistance to microsatellite stabilization was largely confined to mononucleotide repeat sequences. Control (MMR-proficient) cells showed no changes in microsatellite status with or without treatment. The relative dose-dependent stabilization selection was: ortho-NO-ASA approximate to para-NO-ASA > meta-NO-ASA >> ASA. Moreover, the doses required for stabilization by the ortho- and para-NO-ASA were 300- to 3,000-fold lower than ASA. These results suggest that NO-ASA derivatives may be more effective at suppressing MSI in MMR-deficient cell lines than ASA and should be considered for chemopreventive trials with HNPCC carriers. C1 Ohio State Univ, Ctr Comprehens Canc & Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43026 USA. Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. Klinikum Kassel, Inst Pathol, Kassel, Germany. TARGOS Mol Pathol GmbH, Kassel, Germany. SUNY Stony Brook, Div Canc Prevent, Stony Brook, NY 11794 USA. NIH, NCI, DCP, Div Canc Prevent, Bethesda, MD 20892 USA. RP Fishel, R (reprint author), Ohio State Univ, Ctr Comprehens Canc & Med Ctr, Dept Mol Virol Immunol & Med Genet, 400 W 12th Ave, Columbus, OH 43026 USA. EM rfishel@osu.edu NR 31 TC 10 Z9 10 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2007 VL 67 IS 22 BP 10966 EP 10975 DI 10.1158/0008-5472.CAN-07-2562 PG 10 WC Oncology SC Oncology GA 232UA UT WOS:000251044000042 ER PT J AU Shi, Z Peng, XX Kim, IW Shukla, S Si, QS Robey, RW Bates, SE Shen, T Ashby, CR Fu, LW Ambudkar, SV Chen, ZS AF Shi, Zhi Peng, Xing-Xiang Kim, In-Wha Shukla, Suneet Si, Qiu-Sheng Robey, Robert W. Bates, Susan E. Shen, Tong Ashby, Charles R., Jr. Fu, Li-Wu Ambudkar, Suresh V. Chen, Zhe-Sheng TI Erlotinib (Tarceva, OSI-774) antagonizes ATP-bInding cassette subfamily B member 1 and ATP-binding cassette subfamily G member 2-mediated drug resistance SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; HUMAN P-GLYCOPROTEIN; CELL LUNG-CANCER; MULTIDRUG-RESISTANCE; ACQUIRED MUTATIONS; CATALYTIC CYCLE; IN-VIVO; ABCG2; GEFITINIB AB It has been reported that gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has the ability to modulate the function of certain ATP-binding cassette (ABC) transporters and to reverse ABC subfamily B member I (ABCB1; P-glycoprotein)- and ABC subfamily G member 2 (ABCG2; breast cancer resistance protein/mitoxantrone resistance protein) -mediated multidrug resistance (MDR) in cancer cells. However, it is unknown whether other EGFR TKIs have effects similar to that of gefitinib. In the present study, we have investigated the interaction of another EGFR TKI, erlotinib, with selected ABC drug transporters. Our findings show that erlotinib significantly potentiated the sensitivity of established ABCB1 or ABCG2 substrates and increased the accumulation of paclitaxel or mitoxantrone in ABCB1- or ABCG2-overexpressing cells. Furthermore, erlotinib did not significantly alter the sensitivity of non-ABCB1 or non-ABCG2 substrates in all cells and was unable to reverse MRP1-mediated MDR and had no effect on the parental cells. However, erlotinib remarkably inhibited the transport of E(2)17 beta G and methotrexate by ABCG2. In addition, the results of ATPase assays show that erlotinib stimulated the ATPase activity of both ABCB1 and ABCG2. Interestingly, erlotinib slightly inhibited the photolabeling of ABCB1 with [1251] iodoarylazidoprazosin (IAAP) at high concentration, but it did not inhibit the photolabeling of ABCG2 with LAAP. Overall, we conclude that erlotinib reverses ABCB1- and ABCG2-mediated MDR in cancer cells through direct inhibition of the drug efflux function of ABCB1 and ABCG2. These findings may be useful for cancer combinational therapy with erlotinib in the clinic. C1 Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Guangzhou 510060, Peoples R China. St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Member Coremaugh Hlth Syst, Mem Med Ctr, Dept Pathol, Johnstown, PA USA. RP Shi, Z (reprint author), Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Guangzhou 510060, Peoples R China. EM Fulw@mail.sysu.edu.cn; Chenz@stjohns.edu RI shukla, suneet/B-4626-2012; Shen, Tong/C-8853-2012 FU Intramural NIH HHS NR 43 TC 179 Z9 187 U1 2 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2007 VL 67 IS 22 BP 11012 EP 11020 DI 10.1158/0008-5472.CAN-07-2686 PG 9 WC Oncology SC Oncology GA 232UA UT WOS:000251044000047 PM 18006847 ER PT J AU Gutierrez, LF de Silva, R Ozturk, C Sonmez, M Stine, AM Raval, AN Raman, VK Sachdev, V Aviles, RJ Waclawiw, MA McVeigh, ER Lederman, RJ AF Gutierrez, Luis F. de Silva, Ranil Ozturk, Cengizhan Sonmez, Merdim Stine, Annette M. Raval, Amish N. Raman, Venkatesh K. Sachdev, Vandana Aviles, Ronnier J. Waclawiw, Myron A. McVeigh, Elliot R. Lederman, Robert J. TI Technology preview: X-ray fused with magnetic resonance during invasive cardiovascular procedures SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE catheterization; magnetic resonance imaging; stereotactic surgery; image guided intervention; myocardial biopsy; chronic total occlusion ID COMPUTED TOMOGRAPHIC-IMAGES; REAL-TIME; CATHETER ABLATION; SWINE MODEL; LEFT ATRIAL; REGISTRATION; MR; INTERVENTION; MOTION; DEFORMATION AB Background: We have developed and validated a system for real-time X-ray fused with magnetic resonance imaging, MRI (XFM), to guide catheter procedures with high spatial precision. Our implementation overlays roadmaps-MRI-derived soft-tissue features of interest-onto conventional X-ray fluoroscopy. We report our initial clinical experience applying XFM, using external fiducial markers, electrocardiogram (ECG)-gating, and automated real-time correction for gantry and table movement. Methods: This prospective case series for technical development was approved by the NHLBI Institutional Review Board and included 19 subjects. Multimodality external fiducial markers were affixed to patients' skin before MRI, which included contrast-enhanced, 3D T1-weighted, or breath-held and ECG-gated 2D steady state free precession imaging at 1.5T. MRI-derived roadmaps were manually segmented while patients were transferred to a calibrated X-ray fluoroscopy system. Image spaces were registered using the fiducial markers and thereafter permitted unrestricted gantry rotation, table panning, and magnification changes. Static and ECG-gated MRI data were transformed from 3D to 2D to correspond with gantry and table position and combined with live X-ray images. Results: Clinical procedures included graft coronary arteriography, right ventricular free-wail biopsy, and iliac and femoral artery recanalization and stenting. MRI roadmaps improved operator confidence, and in the biopsy cases, outperformed the best available alternative imaging modality. Registration errors were increased when external fiducial markers were affixed to more mobile skin positions, such as over the abdomen. Conclusion: XFM using external fiducial markers is feasible during X-ray guided catheter treatments. Multimodality image fusion may prove a useful adjunct to invasive cardiovascular procedures. (c) 2007 Wiley-Liss, Inc. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. Bogazici Univ, Inst Biomed Engn, Istanbul, Turkey. NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Lederman, RJ (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10,Room 2C713, Bethesda, MD 20892 USA. EM lederman@nhlbi.nih.gov RI Ozturk, Cengizhan/A-6177-2016; OI Ozturk, Cengizhan/0000-0002-6966-0774; lederman, robert/0000-0003-1202-6673 FU Intramural NIH HHS [Z01 HL005062-05]; NHLBI NIH HHS [Z01 HL004608, Z01 HL005062, Z01-HL004608-06, Z01-HL005062-04] NR 22 TC 26 Z9 27 U1 0 U2 3 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 NOV 15 PY 2007 VL 70 IS 6 BP 773 EP 782 DI 10.1002/ccd.21352 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 238JD UT WOS:000251442700001 PM 18022851 ER PT J AU Conti, C Seiler, JA Pommier, Y AF Conti, Chiara Seiler, Jennifer A. Pommier, Yves TI The mammalian DNA replication elongation checkpoint - Implication of Chk1 and relationship with origin firing as determined by single DNA molecule and single cell analyses SO CELL CYCLE LA English DT Article DE DNA replication; molecular combing; fork progression checkpoint; S phase checkpoint; camptothecin; topoisomerase; ATR/Chk1 ID DOUBLE-STRAND BREAKS; TOPOISOMERASE-I; S-PHASE; SACCHAROMYCES-CEREVISIAE; INTERACTING PROTEIN; CLEAVAGE COMPLEXES; FISSION YEAST; HISTONE H2AX; ACTIVATION; PHOSPHORYLATION AB The regulation of DNA replication initiation is well documented, for both unperturbed and damaged cells. The regulation of elongation, or fork velocity, however, has only recently been revealed with the advent of new techniques allowing us to view DNA replication at the single cell and single DNA molecule levels. Normally in S phase, the progression of replication forks and their stability are regulated by the ATR-Claspin-Chk1 pathway. We recently showed that replication fork velocity varies across the human genome in normal and cancer cells, but that the velocity of a given fork is positively correlated with the distance between origins on the same DNA fiber. 19 Accordingly, in DNA replication-deficient Bloom's syndrome cells, reduced fork velocity is associated with an increased density of replication origins. 21 Replication elongation is also regulated in response to DNA damage. In human colon carcinoma cells treated with the topoisomerase I inhibitor camptothecin, DNA replication is inhibited both at the level of initiation and at the level of elongation through a Chk1-dependent checkpoint mechanism. 10 Together, these new findings demonstrate that replication fork velocity (fork progression) is coordinated with inter-origin distance and that it can be actively slowed down by Chk1-dependent mechanisms in response to DNA damage. Thus, we propose that the intra-S phase checkpoint consist of at least three elements: (1) stabilization of damaged replication forks; (2) suppression of firing of late origins; and (3) arrest of normal ongoing forks to prevent further DNA lesions by replication of a damaged DNA template. C1 [Conti, Chiara; Seiler, Jennifer A.; Pommier, Yves] NIH, Natl Canc Inst, Ctr Canc, Mol Pharmacol Lab, Bethesda, MD USA. RP Pommier, Y (reprint author), NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Intramural NIH HHS NR 55 TC 50 Z9 52 U1 0 U2 3 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 NOV 15 PY 2007 VL 6 IS 22 BP 2760 EP 2767 PG 8 WC Cell Biology SC Cell Biology GA 240VC UT WOS:000251615300007 PM 17986860 ER PT J AU Friedman, J Nottingham, L Duggal, P Pernas, FG Yan, B Yang, XP Chen, Z Van Waes, C AF Friedman, Jay Nottingham, Liesl Duggal, Praveen Pernas, Francisco G. Yan, Bin Yang, Xin Ping Chen, Zhong Van Waes, Carter TI Deficient TP53 expression, function, and cisplatin sensitivity are restored by quinacrine in head and neck cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; NF-KAPPA-B; HUMAN-PAPILLOMAVIRUS; PROANGIOGENIC CYTOKINES; ACRIDINE-DERIVATIVES; GROWTH-FACTOR; ACTIVATE P53; MULTIPLE; TUMORS; AGENTS AB Purpose: To determine the nature and potential pharmacologic reversibility of deficient TP53 expression and function in head and neck squamous cell carcinomas (HNSCC) with wild-type TP53, previously associated with decreased sensitivity to cisplatin therapy. Experimental Design: TP53 genotype, mRNA and protein expression, TP53-induced p2l expression, and TP53 DNA-binding and reporter gene function were determined in a panel of nine previously characterized HNSCC cell lines from the University of Michigan squamous cell carcinoma (UM-SCC) series. The genotoxic drug doxorubicin and the anti-inflammatory and antimalarial drug quinacrine, previously identified as inducers of TP53, were used to examine the nature and potential reversibility of deficient TP53 expression and function. The specific role of inducibleTP53 on function and cellular proliferation was confirmed using selectiveTP53 inhibitor pifithrin-alpha or short hairpin RNA knockdown. The capability of quinacrine to sensitize HNSCC to the cytotoxic effects of cisplatin was assessed. Results: UM-SCC cell lines with wild-type TP53 genotype underexpressed TP53 mRNA and protein when compared with normal human keratinocytes or UM-SCC with mutant TP53. Although doxorubicin failed to induce TP53 expression or functional activity, quinacrine induced TP53 mRNA and protein expression, increased TP53 reporter activity and p2l protein expression, and induced growth inhibition in these wild-type TP53 cell lines. Quinacrine-induced TP53 reporter activity and growth suppression were attenuated by pifithrin-alpha and TP53 short hairpin RNA knockdown. Furthermore, quinacrine sensitized UM-SCC to cisplatin in vitro. Conclusions: Deficient TP53 mRNA and protein expression underlies decreased function in a subset of HNSCC with wild-type TP53 and can be restored together with cisplatin sensitization by quinacrine. C1 NIH, Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Tumor Biol Sect, Bethesda, MD USA. RP Van Waes, C (reprint author), NIH, Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [DC 00016] NR 49 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 NOV 15 PY 2007 VL 13 IS 22 BP 6568 EP 6578 DI 10.1158/1078-0432.CCR-07-1591 PN 1 PG 11 WC Oncology SC Oncology GA 235AY UT WOS:000251207100005 PM 18006756 ER PT J AU Annunziata, CM Kleinberg, L Davidson, B Berner, A Gius, D Tchabo, N Steinberg, SM Kohn, EC AF Annunziata, Christina M. Kleinberg, Lilach Davidson, Ben Berner, Aasmund Gius, David Tchabo, Nana Steinberg, Seth M. Kohn, Elise C. TI BAG-4/SODD and associated antiapoptotic proteins are linked to aggressiveness of epithelial ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID NECROSIS-FACTOR-ALPHA; HEAT-SHOCK PROTEINS; BCL-X-L; DEATH-DOMAINS; CELL-LINE; PROGNOSTIC-SIGNIFICANCE; EXPRESSION; CARCINOMA; TUMOR; CISPLATIN AB Purpose: We hypothesized that elevated expression in ovarian cancer of the BAG family of prosurvival proteins and associated partners would be associated with clinical features of aggressiveness in ovarian cancer. Experimental Design: Expression patterns of BAG-1, BAG-3, BAG-4, and Bcl-xL were determined by immunohistochemical analysis of tissue samples obtained at diagnosis from 28 women with stage III or stage IV ovarian cancer treated with cisplatin, paclitaxel, and cyclophosphamide after initial cytoreduction. Association of these proteins, BAG-6, heat shock protein 70 (Hsp70), Hsp27, and Bcl-2, with clinical variables was tested in ovarian cancer tissue arrays from Gynecologic Oncology Group tissue bank. Results: A statistically significant relationship was found between elevated cytoplasmic expression of BAG-4 and improved overall (P = 0.0002) and progression-free survival (P = 0.003) in the prospectively collected samples. Bcl-2 staining was significantly more frequent on the tissue array in lower stage (P = 0.005) and grade (P = 0.0009) tumors, whereas Hsp70 was prominent in higher grade cases (P = 0.002). Furthermore, Bcl-xL was more closely associated with serous compared with endometrioid ovarian cancers (P = 0.004). Conclusion: Unexpectedly, cytoplasmic expression of BAG-4 and Bcl-2 marked less aggressive ovarian cancer, whereas nuclear Hsp70 suggested more aggressive behavior. Bcl-xL may play a more prominent function in the pathology of serous histology ovarian cancers compared with the enclometrioid subtype. The findings presented here support involvement of these proteins in the propagation of ovarian cancer and provide a basis for the development of molecular therapeutics modulating these survival pathways. C1 Natl Canc Inst, Med Oncol Branch, Bethesda, MD USA. Natl Canc Inst, Mol Signalling Sect, Pathol Lab, Bethesda, MD USA. Natl Canc Inst, Radiat Oncol Branch, Bethesda, MD USA. Natl Canc Inst, Ctr Canc Res, NIH, Biostat & Data Management Sect, Bethesda, MD USA. Rikshospitalet Radiumhospitalet Med Ctr, Pathol Clin, Oslo, Norway. RP Annunziata, CM (reprint author), Natl Canc Inst, NIH, Med Oncol Branch, Bldg 10, Room 4N115, 10 Ctr Dr, Bethesda, MD 20892 USA. EM annunzic@mail.nih.gov RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 FU Intramural NIH HHS NR 46 TC 18 Z9 23 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 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2007 VL 13 IS 22 BP 6585 EP 6592 DI 10.1158/1078-0432.CCR-07-0327 PN 1 PG 8 WC Oncology SC Oncology GA 235AY UT WOS:000251207100007 PM 18006758 ER PT J AU Barrett, T Koyama, Y Hama, Y Ravizzini, G Shin, IS Jang, BS Paik, CH Urano, Y Choyke, PL Kobayashi, H AF Barrett, Tristan Koyama, Yoshinori Hama, Yukihiro Ravizzini, Gregory Shin, In Soo Jang, Beom-Su Paik, Chang H. Urano, Yasuteru Choyke, Peter L. Kobayashi, Hisataka TI In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CANCER; CELLS; BIODISTRIBUTION; PROTEINS; OVARIAN; MICE AB Purpose: Epidermal growth factor receptors (EGFR) play an important role in tumorigenesis and, therefore, have become targets for new molecular therapies. Here, we use a '' cocktail '' of optically labeled monoclonal antibodies directed against EGFR-1 (HER1) and EGFR-2 (HER2) to distinguish tumors by their cell surface expression profiles. Experimental Design: In vivo imaging experiments were done in tumor-bearing mice following s.c. injection of A431 (overexpressing HER1), NIH3T3/HER2+ (overexpressing HER2), and Balb3T3/DsRed (non-expression control) cell lines. After tumor establishment, a cocktail of optically labeled antibodies: Cy5.5-labeled cetuximab (anti-HER1) and Cy7-labeled trastuzumab (anti-HER2) was i.v. injected. In vivo and ex vivo fluorescence imaging was done. For comparison with radionuclide imaging, experiments were undertaken using (111)Indium-labeled antibodies. Additionally, a '' blinded '' diagnostic study was done for mice bearing one tumor type. Results: In vivo spectral fluorescent molecular imaging of 14 mice with three tumor types clearly differentiated tumors using the cocktail of optically labeled antibodies both in vivo and ex vivo. Twenty-four hours after injection, A431 and NIH3T3/HER2+ tumors were detected distinctly by their peak on Cy5.5 and Cy7 spectral images, respectively; radionuclide imaging was unable to clearly distinguish tumors at this time point. In blinded single tumor experiments, investigators were able to correctly diagnose a total of 40 tumors. Conclusion: An in vivo imaging technique using an antibody cocktail simultaneously differentiated two tumors expressing distinct EGFRs and enabled an accurate characterization of each subtype. C1 Ctr Canc Res, Natl Canc Inst, Mol Imaging Program, Bethesda, MD USA. NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan. RP Kobayashi, H (reprint author), Ctr Canc Res, Natl Canc Inst, NIH, Mol Imaging Program, Bldg 10, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov RI Urano, Yasuteru/H-1380-2012 FU Intramural NIH HHS NR 24 TC 73 Z9 73 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2007 VL 13 IS 22 BP 6639 EP 6648 DI 10.1158/1078-0432.CCR-07-1119 PN 1 PG 10 WC Oncology SC Oncology GA 235AY UT WOS:000251207100014 PM 17982120 ER PT J AU Downey, SG Klapper, JA Smith, FO Yang, JC Sherry, RM Royal, RE Kammula, US Hughes, MS Allen, TE Levy, CL Yellin, M Nich, G White, DE Steinberg, SM Rosenberg, SA AF Downey, Stephanie G. Klapper, Jacob A. Smith, Franz O. Yang, James C. Sherry, Richard M. Royal, Richard E. Kammula, Udai S. Hughes, Marybeth S. Allen, Tamika E. Levy, Catherine L. Yellin, Michael Nich, Geoffrey White, Donald E. Steinberg, Seth M. Rosenberg, Steven A. TI Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade SO CLINICAL CANCER RESEARCH LA English DT Article ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; COLONY-STIMULATING FACTOR; T-CELL PROLIFERATION; CTLA-4-MEDIATED INHIBITION; TUMOR-IMMUNOTHERAPY; REGULATORY CELLS; AUTOIMMUNITY; ACTIVATION; CANCER; ANTIBODY AB Purpose: CTIL-associated antigen 4 (CTLA-4) can inhibit T-cell activation and helps maintain peripheral self-tolerance. Previously, we showed immune-related adverse events (IRAE) and objective, durable clinical responses in patients with metastatic melanoma treated with CTLA-4 blockade. We have now treated 139 patients in two trials and have sufficient follow-up to examine factors associated with clinical response. Experimental Design: A total of 139 patients with metastatic melanoma were treated: 54 patients received ipilimumab in conjunction with peptide vaccinations and 85 patients were treated with intra-patient dose escalation of ipilimumab and randomized to receive peptides in accordance with HLA-A*0201 status. Results: Three patients achieved complete responses (CR; ongoing at 29+, 52+, and 53+ months); an additional 20 patients achieved partial responses (PR) for an overall objective response rate of 17%. The majority of patients (62%, 86 of 139) developed some form of IRAE, which was associated with a greater probability of objective antitumor response (P = 0.0004); all patients with CR had more severe IRAEs. Prior therapy with IFNU-2b was a negative prognostic factor, whereas prior high-dose interleukin-2 did not significantly affect the probability of response. There were no significant differences in the rate of clinical response or development of IRAEs between the two trials. The duration of tumor response was not affected by the use of high-dose steroids for abrogation of treatment-related toxicities (P = 0.23). There were no treatment- related deaths. Conclusion: In patients with metastatic melanoma, ipilimumab can induce durable objective clinical responses, which are related to the induction of IRAEs. C1 Natl Canc Inst, NIH, Surg Branch, Bethesda, MD 20892 USA. Natl Canc Inst, NIH, Biostat & Data Management Sect, Bethesda, MD USA. Medarex Inc, Princeton, NJ USA. RP Rosenberg, SA (reprint author), Natl Canc Inst, NIH, Surg Branch, Room 3-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM sar@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 37 TC 263 Z9 266 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2007 VL 13 IS 22 BP 6681 EP 6688 DI 10.1158/1078-0432.CCR-07-0187 PN 1 PG 8 WC Oncology SC Oncology GA 235AY UT WOS:000251207100019 PM 17982122 ER PT J AU Liu, W Wu, X Zhang, W Montenegro, RC Fackenthal, DL Spitz, JA Huff, LM Innocenti, F Das, S Cook, EH Cox, NJ Bates, SE Ratain, MJ AF Liu, Wanqing Wu, Xiaolin Zhang, Wei Montenegro, Raquel C. Fackenthal, Donna Lee Spitz, Jared A. Huff, Lyn Mickley Innocenti, Federico Das, Soma Cook, Edwin H., Jr. Cox, Nancy J. Bates, Susan E. Ratain, Mark J. TI Relationship of EGFR mutations, expression, amplification, and polymorphisms to epidermal growth factor receptor inhibitors in the NC160 cell lines SO CLINICAL CANCER RESEARCH LA English DT Article ID LUNG-CANCER; INTRON-1 POLYMORPHISM; GEFITINIB SENSITIVITY; MOLECULAR PREDICTORS; DINUCLEOTIDE REPEAT; CLINICAL-RESPONSE; KINASE DOMAIN; GENE; ERLOTINIB; RESPONSIVENESS AB Purpose: The mechanism of sensitivity and resistance to epidermal growth factor receptor (EGFR) inhibitors is incompletely understood, particularly in cancers other than non - small-cell lung cancer (NSCLC). To understand the variable response to this class of drugs, we used the NCI 60 cancer cell lines. We aimed to determine if there are interactions between EGFR expression, mutations, polymorphisms, and gene amplification, and whether these factors are associated with variability in response to EGFR inhibitors. Experimental Design: The EGFRVIII and tyrosine kinase (TK) domain mutations were examined in the NC160 cancer cell lines. Five polymorphisms, -216G/T, -191C/A, intron 1 (CA)n, R497K, and 2607A/G, were genotyped. EGFR amplification was also assessed with high-density sing single-nucleoticle polymorphism chip and real-time PCR, respectively. The results were correlated with cytotoxicity data for erlotinib and other 11 EGFR inhibitors, as well as other publicly available data for these lines. Results: All 12 inhibitors behaved similarly. No EGFRVIII but putative TK mutations in two cell lines were found. Both mutant cell lines were insensitive to all inhibitors. Meanwhile, response did not correlate with EGFR amplification but with EGFR gene expression, especially in the cell lines with relatively normal gene status. In addition, EGFR expression was associated with the -216G/T polymorphism but not with the intron 1 (CA) n polymorphism. A combination of -216G/T and R497 K polymorphisms was weakly associated with drug response. Conclusions: These observations suggest that in addition to TK mutations, germ-line variability may also contribute to the pharmacodynamics of EGFR inhibitors, particularly when EGFR is genetically normal. C1 Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Chicago, Committee Clin Pharmacol & Pharmacogenet, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. Univ Illinois, Inst Juvenille Res, Dept Psychiat, Chicago, IL 60680 USA. NCI, NIH, Canc Therapeut Branch, Bethesda, MD USA. RP Ratain, MJ (reprint author), Univ Chicago, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM mratain@medicine.bsd.uchicago.edu RI Montenegro, Raquel/I-1260-2013 FU NIGMS NIH HHS [U01 GM 61393, U01 GM 61374] NR 39 TC 46 Z9 48 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 NOV 15 PY 2007 VL 13 IS 22 BP 6788 EP 6795 DI 10.1158/1078-0432.CCR-07-0547 PN 1 PG 8 WC Oncology SC Oncology GA 235AY UT WOS:000251207100032 PM 18006781 ER PT J AU Compton, CC AF Compton, Carolyn C. TI Optimal pathologic staging: Defining stage II disease SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT Santa Monica Conference on Assessing and Treating Early-Stage Colon and Rectal Cancer CY JAN 12-13, 2007 CL Santa Monica, CA ID AMERICAN-JOINT-COMMITTEE; LYMPH-NODE METASTASES; CIRCUMFERENTIAL MARGIN INVOLVEMENT; NONPOLYPOSIS COLORECTAL-CANCER; NEGATIVE COLON-CANCER; ISOLATED TUMOR-CELLS; LARGE BOWEL-CANCER; RECTAL-CANCER; PROGNOSTIC-FACTORS; MULTIVARIATE-ANALYSIS AB Tumor stage remains the most important determinant of prognosis in colorectal cancer and is the basis of all authoritative patient management guidelines. The pathologic assessment of stage 11 disease is especially critical because it may help to identify patients at additional risk for whom surgery alone may not be curative. Accurate analysis of regional lymph nodes, extent of tumor penetration, and circumferential resection margins constitute the most crucial issues. For assignment of pNO, adequacy of the surgical resection and thoroughness of the lymph node harvest from the resection specimen are both essential. The minimum number of lymph nodes has been variably determined to be between 12 and 18 for assignment of pNO, but the confidence level increases with increasing numbers of nodes examined. The ability of exhaustive analysis of sentinel lymph nodes using special techniques to substitute for an exhaustive lymph node harvest and standard node examination has not been definitively shown. Although special techniques may facilitate the identification of minute amounts of tumor (i.e., isolated tumor cells) in regional lymph nodes, the prognostic significance of such findings remains unclear. Additional stage-independent pathologic features that have been validated as adverse prognostic factors include involvement by tumor of mural lymphovascular channels, venous vessels, or the surgical resection margin of the operative specimen and high tumor grade. The presence of these features may help to identify patients for whom surgery alone will not be curative and adjuvant therapies may be appropriate. C1 NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. RP Compton, CC (reprint author), NCI, Off Biorepositories & Biospecimen Res, 31 Ctr Dr, Bethesda, MD 20892 USA. EM comptcar@mail.nih.gov NR 114 TC 36 Z9 39 U1 1 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 NOV 15 PY 2007 VL 13 IS 22 SU S BP 6862S EP 6870S DI 10.1158/1078-0432.CCR-07-1398 PN 2 PG 9 WC Oncology SC Oncology GA 237TC UT WOS:000251398300003 PM 18006791 ER PT J AU Turner, RR Li, C Compton, CC AF Turner, Roderick R. Li, Carolyn Compton, Carolyn C. TI Newer pathologic assessment techniques for colorectal carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT Santa Monica Conference on Assessing and Treating Early-Stage Colon and Rectal Cancer CY JAN 12-13, 2007 CL Santa Monica, CA ID LYMPH-NODE MICROMETASTASES; REVISED BETHESDA GUIDELINES; COLON-CANCER PATIENTS; ISOLATED TUMOR-CELLS; MICROSATELLITE INSTABILITY; DUKES-B; STAGE-II; PROGNOSTIC IMPLICATIONS; MOLECULAR MARKERS; INVASIVE MARGIN AB The pathogenesis of colorectal carcinoma is characterized by progressive genetic abnormalities, which lead to proteomic and cellular changes that determine the cancer malignant phenotype. Phenotypic characteristics seen on histopathologic examination (e.g., tumor stage, histologic grade, and vasoinvasiveness) are essential to planning patient management and should continue to be the major focus of pathologists' efforts. Nonetheless, additional markers that improve the prognostic and predictive power of the pathologic analysis of the primary tumor have been the focus of intense research in recent years. Improved prognostic power may derive from advancements in histopathologic evaluation, more sensitive lymph node staging techniques, and specific molecular analysis methods, such as genetic tests or immunophenotypic profiles. Histopathologic improvements are needed to better standardize histologic grade determination and recognize tumor budding at the invasive front as a marker of aggressive biological behavior and an adverse parameter. Ultrastaging of mesenteric lymph nodes remains a controversial area. Genotypic studies are well developed in the areas of microsatellite instability and chromosome 18q deletion/loss of heterozygosity. Immunophenotypic studies are available in a range of areas including tumor suppressor gene/oncogene expression, proliferation/apoptosis, angiogenesis, and cell adhesion and signaling. Gene expression profiles identified by microarray techniques may help to subtype the large category of microsatellite-stable colorectal carcinoma and define immunophenotypic panels to subclassify tumors into prognostic and therapeutic groups. This brief review discusses the most promising of these approaches and evidence supporting their potential clinical utility. C1 St Johns Hlth Ctr, John Wayne Canc Inst, Dept Pathol, Santa Monica, CA 90404 USA. St Johns Hlth Ctr, Dept Pathol, Santa Monica, CA USA. NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD USA. RP Turner, RR (reprint author), St Johns Hlth Ctr, John Wayne Canc Inst, Dept Pathol, 1328 22nd St, Santa Monica, CA 90404 USA. EM r.turner@stjohns.org NR 61 TC 27 Z9 27 U1 1 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 NOV 15 PY 2007 VL 13 IS 22 SU S BP 6871S EP 6876S DI 10.1158/1078-0432.CCR-07-1151 PN 2 PG 6 WC Oncology SC Oncology GA 237TC UT WOS:000251398300004 PM 18006792 ER PT J AU Howitz, M Krause, TG Simonsen, JB Hoffmann, S Frisch, M Nielsen, NM Robbins, J Schneerson, R Molbak, K Miller, MA AF Howitz, Michael Krause, Tyra Grove Simonsen, Jacob Brunbjerg Hoffmann, Steen Frisch, Morten Nielsen, Nete Munk Robbins, John Schneerson, Rachel Molbak, Kare Miller, Mark A. TI Lack of association between group B meningococcal disease and autoimmune disease SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MENINGITIDIS CAPSULAR POLYSACCHARIDE; ANTIBODY; VACCINES; SYSTEM; EPIDEMIOLOGY; COHORT; ROLES; ASSAY; NCAM AB Background. The capsular polysaccharide of group B meningococci (GBM) is structurally identical to a polysaccharide found on neural cell adhesion molecules in humans. This structural identity has raised concern that a vaccine based on the GBM capsular polysaccharide might induce autoimmune disease in vaccinated persons. Because systemic infection with GBM induces serum antibody in adults, we investigated whether persons with a history of GBM disease are at increased risk of developing autoimmune diseases. Methods. The entire Danish population constituted our study cohort of 7,467,001 individuals, who were observed for autoimmune diseases from 1977 through 2004. At-risk years were counted as the number of uninfected years prior to the first recorded diagnosis of meningococcal disease but changed to person-years at risk at the diagnosis of GBM disease (2984 subjects) or group C meningococcal disease (914 patients). Ratios of incidence rates of autoimmune disease served as measures of the relative risk. Results. Persons with a history of GBM disease experienced a total of 37,290 person-years at risk, ranging from 11 days to 31 years at risk after the onset of GBM disease, during which 49 cases of autoimmune disease occurred. Persons with GBM disease had no increased risk of autoimmune diseases, either compared with persons with a history of group C meningococcal disease (incidence rate ratio, 0.9; 95% confidence interval, 0.5-1.4) or compared with persons without a history of meningococcal disease (incidence rate ratio, 1.1; 95% confidence interval, 0.8-1.5). Conclusions. Our findings suggest that invasive disease caused by GBM is not associated with autoimmune diseases in humans for up to 31 years after meningococcal disease and should lessen concerns regarding the development of a capsular-based GBM vaccine. C1 Statens Serum Inst, Dept Epidemiol, DK-2300 Copenhagen, Denmark. Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. Statens Serum Inst, Dept Bacteriol Mycol & Parasitol, DK-2300 Copenhagen, Denmark. NICHHD, Dev & Mol Immun Lab, Bethesda, MD 20892 USA. NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Howitz, M (reprint author), Artillerivej 5, DK-2300 Copenhagen, Denmark. EM how@ssi.dk RI Frisch, Morten/E-9206-2016; OI Frisch, Morten/0000-0002-3864-8860; Molbak, Kare/0000-0002-3100-4990 NR 28 TC 18 Z9 18 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 NOV 15 PY 2007 VL 45 IS 10 BP 1327 EP 1334 DI 10.1086/522190 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 222RY UT WOS:000250315900012 PM 17968829 ER PT J AU Wahl, MB Deng, C Lewandoski, M Pourquie, O AF Wahl, Matthias B. Deng, Chuxia Lewandoski, Mark Pourquie, Olivier TI FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis SO DEVELOPMENT LA English DT Article DE FGF; somite; segmentation; clock; oscillation; vertebra ID RETINOIC-ACID; PRESOMITIC MESODERM; TARGETED DISRUPTION; PROSPECTIVE SOMITES; GENE-EXPRESSION; OPPOSING FGF; BODY AXIS; EMBRYO; INACTIVATION; PATTERN AB Fibroblast growth factor ( FGF) signaling plays a crucial role in vertebrate segmentation. The FGF pathway establishes a posterior-to-anterior signaling gradient in the presomitic mesoderm ( PSM), which controls cell maturation and is involved in the positioning of segmental boundaries. In addition, FGF signaling was shown to be rhythmically activated in the PSM in response to the segmentation clock. Here, we show that conditional deletion of the FGF receptor gene Fgfr1 abolishes FGF signaling in the mouse PSM, resulting in an arrest of the dynamic cyclic gene expression and ultimately leading to an arrest of segmentation. Pharmacological treatments disrupting FGF signaling in the PSM result in an immediate arrest of periodic WNT activation, whereas NOTCH-dependent oscillations stop only during the next oscillatory cycle. Together, these experiments provide genetic evidence for the role of FGF signaling in segmentation, and identify a signaling hierarchy controlling clock oscillations downstream of FGF signaling in the mouse. C1 Stowers Inst Med Res, Kansas City, MO 64110 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Canc & Dev Biol, NIH, Frederick, MD 21702 USA. Howard Hughes Med Inst, Kansas City, MO 64110 USA. RP Pourquie, O (reprint author), Stowers Inst Med Res, Kansas City, MO 64110 USA. EM olp@stowers-institute.org RI deng, chuxia/N-6713-2016 NR 42 TC 99 Z9 103 U1 1 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD NOV 15 PY 2007 VL 134 IS 22 BP 4033 EP 4041 DI 10.1242/dev.009167 PG 9 WC Developmental Biology SC Developmental Biology GA 224TG UT WOS:000250468700009 PM 17965051 ER PT J AU Hamshere, ML Holmans, PA Avramopoulos, D Bassett, SS Blacker, D Bertram, L Wiener, H Rochberg, N Tanzi, RE Myers, A Vrieze, FWD Go, R Fallin, D Lovestone, S Hardy, J Goate, A O'Donovan, M Williams, J Owen, MJ AF Hamshere, Marian L. Holmans, Peter A. Avramopoulos, Dimitrios Bassett, Susan S. Blacker, Deborah Bertram, Lars Wiener, Howard Rochberg, Nan Tanzi, Rudolph E. Myers, Amanda Vrieze, Fabienne Wavrant-De Go, Rodney Fallin, Daniele Lovestone, Simon Hardy, John Goate, Alison O'Donovan, Michael Williams, Julie Owen, Michael J. TI Genome-wide linkage analysis of 723 affected relative pairs with late-onset Alzheimer's disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID PARENT-OF-ORIGIN; APOLIPOPROTEIN-E; COMPLEX TRAITS; LOCUS; GENE; CHROMOSOME-10; ASSOCIATION; COVARIATE; SCREEN; AGE AB Previous attempts to identify genetic loci conferring risk for late-onset Alzheimer's disease (LOAD) through linkage analysis have observed some regions of linkage in common. However, due to the sometimes-considerable overlap between the samples, some of these reports cannot be considered to be independent replications. In order to assess the strength of the evidence for linkage and to obtain the best indication of the location of susceptibility genes, we have amalgamated three large samples to give a total of 723 affected relative pairs (ARPs). Multipoint, model-free ARP linkage analysis was performed. Genome-wide significant evidence for linkage was observed on 10q21.2 (LOD = 3.3) and genome-wide suggestive evidence was observed on 9q22.33 (LOD = 2.5) and 19q13.32 (LOD = 2.0). One further region on 9p21.3 was identified with an LOD score > 1. We observe no evidence to suggest that more than one locus is responsible for the linkage to 10q21.2, although this linked region may harbour more than one susceptibility gene. Evidence of allele-sharing heterogeneity between the original collection sites was observed on chromosome 9 but not on chromosome 10 or 19. Evidence for an interaction was observed between loci on chromosomes 10 and 19. Where samples overlapped, the genotyping consistency was high, estimated to average at 97.3%. Our large-scale linkage analysis consolidates clear evidence for a susceptibility locus for LOAD on 10q21.2. C1 Cardiff Univ, Sch Med, Dept Med Psychol, Cardiff CF14 4XN, S Glam, Wales. Cardiff Univ, Biostat & Bioinformat Unit, Sch Med, Cardiff CF14 4XN, S Glam, Wales. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Gerontol Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Alabama, Dept Epidemiol, Birmingham, AL USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Coral Gables, FL 33124 USA. NIA, Neurogenet Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Kings Coll London, Inst Psychiat, MRC, Ctr Neurodegenerat Res, London SE5 8AF, England. UCL, Dept Mol Neurosci, Inst Neurol, London WC1N 3BG, England. UCL, Reta Lila Weston Labs, Inst Neurol, London WC1N 3BG, England. RP Owen, MJ (reprint author), Cardiff Univ, Sch Med, Dept Med Psychol, Heath Pk, Cardiff CF14 4XN, S Glam, Wales. EM owenmj@cardiff.ac.uk RI Lovestone, Simon/E-8725-2010; Myers, Amanda/B-1796-2010; turton, miranda/F-4682-2011; Hardy, John/C-2451-2009; Avramopoulos, Dimitrios/J-4392-2012; Holmans, Peter/F-4518-2015; Bertram, Lars/K-3889-2015; OI Myers, Amanda/0000-0002-3100-9396; Holmans, Peter/0000-0003-0870-9412; Bertram, Lars/0000-0002-0108-124X; O'Donovan, Michael/0000-0001-7073-2379 FU Medical Research Council [G0300429, G0701075, G9810900]; NIA NIH HHS [U24 AG021886]; Parkinson's UK [G-0907] NR 46 TC 32 Z9 32 U1 0 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 NOV 15 PY 2007 VL 16 IS 22 BP 2703 EP 2712 DI 10.1093/hmg/ddm224 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 227SZ UT WOS:000250679400006 PM 17725986 ER PT J AU Bischof, JM Stewart, CL Wevrick, R AF Bischof, Jocelyn M. Stewart, Colin L. Wevrick, Rachel TI Inactivation of the mouse Magel2 gene results in growth abnormalities similar to Prader-Willi syndrome SO HUMAN MOLECULAR GENETICS LA English DT Article ID NECDIN-DEFICIENT MICE; POSTNATAL LETHALITY; BODY-COMPOSITION; HORMONE THERAPY; ADIPOSE-TISSUE; OBESE SUBJECTS; CELL-DEATH; DISRUPTION; DELETION; NEURONS AB Prader-Willi syndrome (PWS) is an imprinted genetic obesity disorder characterized by abnormalities of growth and metabolism. Multiple mouse models with deficiency of one or more PWS candidate genes have partially correlated individual genes with aspects of the PWS phenotype, although the genetic origin of defects in growth and metabolism has not been elucidated. Gene-targeted mutation of the PWS candidate gene Magel2 in mice causes altered circadian rhythm output and reduced motor activity. We now report that Magel2-null mice exhibit neonatal growth retardation, excessive weight gain after weaning, and increased adiposity with altered metabolism in adulthood, recapitulating fundamental aspects of the PWS phenotype. Magel2-null mice provide an important opportunity to examine the physiological basis for PWS neonatal failure to thrive and post-weaning weight gain and for the relationships among circadian rhythm, feeding behavior, and metabolism. C1 Univ Alberta, Dept Med Genet, Edmonton, AB T6G 2H7, Canada. Natl Canc Inst, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Wevrick, R (reprint author), Univ Alberta, Dept Med Genet, 8-16 Med Sci Bldg, Edmonton, AB T6G 2H7, Canada. EM rachel.wevrick@ualberta.ca OI Wevrick, Rachel/0000-0002-3343-5794 FU NIDDK NIH HHS [DK5963, DK59630] NR 37 TC 69 Z9 69 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2007 VL 16 IS 22 BP 2713 EP 2719 DI 10.1093/hmg/ddm225 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 227SZ UT WOS:000250679400007 PM 17728320 ER PT J AU Graziewicz, MA Bienstock, RJ Copeland, WC AF Graziewicz, Maria A. Bienstock, Rachelle J. Copeland, William C. TI The DNA polymerase gamma Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine SO HUMAN MOLECULAR GENETICS LA English DT Article ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; SUBSTANTIA-NIGRA NEURONS; P55 ACCESSORY SUBUNIT; STEADY-STATE KINETICS; MITOCHONDRIAL-DNA; OXIDATIVE DAMAGE; SACCHAROMYCES-CEREVISIAE; NUCLEIC-ACIDS; REVERSE-TRANSCRIPTASE; NUCLEOTIDE INSERTION AB Mitochondrial DNA is replicated and repaired by DNA polymerase gamma (pol gamma), encoded by the POLG gene. The Y955C substitution in POLG leads to autosomal dominant progressive external ophthalmoplegia (PEO) with other severe phenotypes. PEO patients with this mutation can further develop parkinsonism or premature ovarian failure. Mouse and yeast models with this mutation show enhanced amounts of oxidative lesions and increased mtDNA damage. In DNA pol gamma, Tyr955 plays a critical role in catalysis and high fidelity DNA synthesis. 7,8-dihydro-8-oxo-2 '-deoxyguanosine (8-oxo-dG) is one of the most common oxidative lesions in DNA and can promote transversion mutations. Mitochondria are thought to be a major source of endogenous reactive oxygen species that can react with dG to form 8-oxo-dG as one of the more common products. DNA polymerases can mitigate mutagenesis by 8-oxo-dG through allosteric interactions from amino acid side chains, which limit the anti-conformation of the 8-oxo-dG template base during translesion DNA synthesis. Here, we show that the Y955C pol g displays relaxed discrimination when either incorporating 8-oxo-dGTP or translesion synthesis opposite 8-oxo-dG. Molecular modeling and biochemical analysis suggest that this residue, Tyr955, in conjunction with Phe961 helps attenuate the anti-conformation in human pol g for error free bypass of 8-oxo-dG and substitution to Cys allows the mutagenic syn conformation. Collectively, these results offer a biochemical link between the observed oxidative stress in model systems and parkinsonism in patients, suggesting that patients harboring the Y955C POLG mutation may undergo enhanced oxidative stress and DNA mutagenesis. C1 Natl Inst Environm Hlth Sci, Mol Genet Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Comp Sci Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Copeland, WC (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, Natl Inst Hlth, POB 12233, Res Triangle Pk, NC 27709 USA. EM copelan1@niehs.nih.gov OI Bienstock, Rachelle/0000-0001-5228-3610 FU Intramural NIH HHS [Z01 ES065078-14] NR 68 TC 51 Z9 52 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2007 VL 16 IS 22 BP 2729 EP 2739 DI 10.1093/hmg/ddm227 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 227SZ UT WOS:000250679400009 PM 17725985 ER PT J AU Kuehn, HS Gilfillan, AA AF Kuehn, Hye Sun Gilfillan, Alasdair A. TI G protein-coupled receptors and the modification of Fc epsilon RI-mediated mast cell activation SO IMMUNOLOGY LETTERS LA English DT Review DE mast cells; Fc epsilon RI; G protein-coupled receptors; IgE; antigen; signalling ID A(2B) ADENOSINE RECEPTORS; IGE-DEPENDENT HISTAMINE; PHOSPHOINOSITIDE 3-KINASE; HIGH-AFFINITY; SPHINGOSINE 1-PHOSPHATE; SIGNAL-TRANSDUCTION; RBL-2H3 CELLS; INFLAMMATORY CYTOKINES; EICOSANOID GENERATION; PHOSPHOLIPASE A(2) AB By releasing multiple pro-inflammatory mediators upon activation, mast cells are critical effector cells in the pathogenesis of allergic inflammation. The traditional viewpoint of antigen-dependent mast cell activation is that of a Th-2-driven process whereby antigen-specific IgE molecules are produced by B cells followed by binding of the IgE to high affinity IgE receptors (Fc epsilon RI) expressed on mast cells. Subsequent anti gen-dependent aggregation of the Fc epsilon RI initiates an intracellular signalling cascade that culminates in mediator release. Mast cell responses, including cell growth, survival, chernotaxis, and cell adhesion, however, can also be regulated by other receptors expressed on mast cells. Furthermore, Fc epsilon RI-mediated mast cell mediator release can be significantly modified by ligation of specific classes of these receptors. One such class of receptors is the G protein-coupled receptors (GPCR). In this review, we describe how sub-populations of GPCRs can either enhance or inhibit Fc epsilon RI-mediated mast cell activation depending on the particular G protein utilized for relaying signalling. Furthermore, we discuss the potential mechanisms whereby the signalling responses utilized by the Fc epsilon RI for mast cell activation are influenced by those initiated by GPCRs to produce these diverse responses. Published by Elsevier B.V. C1 NIH, NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Gilfillan, AA (reprint author), NIH, NIAID, Lab Allerg Dis, Bldg 10,Rm 11C206,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. EM agilfillan@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000965-02] NR 129 TC 70 Z9 71 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD NOV 15 PY 2007 VL 113 IS 2 BP 59 EP 69 DI 10.1016/j.imlet.2007.08.007 PG 11 WC Immunology SC Immunology GA 230CF UT WOS:000250852500001 PM 17919738 ER PT J AU Inskip, PD Curtis, RE AF Inskip, Peter D. Curtis, Rochelle E. TI New malignancies following childhood cancer in the United States, 1973-2002 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE second cancers; multiple primary cancers; childhood cancer; epidemiology; surveillance; epidemiology and end results (SEER) registries ID LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; HODGKINS-DISEASE; ALKYLATING-AGENTS; THYROID-CANCER; BREAST-CANCER; 2ND NEOPLASMS; SECONDARY SARCOMAS; POOLED ANALYSIS; NERVOUS-SYSTEM AB The objectives of our study were to quantify risks for developing new malignancies among childhood cancer survivors, identify links between particular types of first and subsequent cancer, and evaluate the possible role of treatment. A cohort of 25,965 2-month survivors of childhood cancer diagnosed in the U.S. during 1973-2002 was identified and followed through SEER cancer registries. Observed -to-expected ratios (O/E) were calculated, and Poisson regression was used to compare risks among treatment groups. Childhood cancer survivors were at nearly 6-fold risk of developing a new cancer relative to the general population (O/E = 5.9, 95% CI: 5.4-6.5). Most common were subsequent primary cancers of the female breast, central nervous system, bone, thyroid gland and soft tissue, as well as cutaneous melanoma and acute non-lymphocytic leukemia (ANLL). The greatest risks of subsequent cancers occurred among patients diagnosed previously with Hodgkin lymphoma (HL), Ewing sarcoma, primitive neuroectodermal tumor, or retinoblastoma. Risk of subsequent solid cancers was higher among persons whose initial treatment for childhood cancer included radiotherapy, whereas the excess of subsequent ANLL was strongly related to chemotherapy. The O/E for subsequent ANLL increased with increasing calendar year of initial cancer diagnosis among survivors of cancers other than HL, most likely due to increasing use of leukemogenic drugs for solid cancers and non-Hodgkin lymphoma. Childhood cancer survivors are at markedly increased risk of developing a variety of new cancers relative to the general population, but the magnitude of excess risk and specific types of second cancer vary widely by type of first cancer. (c) 2007 Wiley-Liss, Inc. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet,NIH, DHHS, Bethesda, MD 20892 USA. RP Inskip, PD (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet,NIH, DHHS, Execut Pl S,Room 7052, Bethesda, MD 20892 USA. EM inskippe@mail.nih.gov NR 62 TC 75 Z9 77 U1 2 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2007 VL 121 IS 10 BP 2233 EP 2240 DI 10.1002/ijc.22827 PG 8 WC Oncology SC Oncology GA 221RN UT WOS:000250245100015 PM 17557301 ER PT J AU Lee, JE Hunter, DJ Spiegelman, D Adami, HO Bernstein, L van den Brandt, PA Buring, JE Cho, E English, D Folsom, AR Freudenheim, JL Gile, GG Giovannucci, E Horn-Ross, PL Leitzmann, M Marshall, JR Mannisto, S McCullough, ML Miller, AB Parker, AS Pietinen, P Rodriguez, C Rohan, TE Schatzkin, A Schouten, LJ Willett, WC Wolk, A Zhang, SM Smith-Warner, SA AF Lee, Jung Eun Hunter, David J. Spiegelman, Donna Adami, Hans-Olov Bernstein, Leslie van den Brandt, Piet A. Buring, Julie E. Cho, Eunyoung English, Dallas Folsom, Aaron R. Freudenheim, Jo L. Gile, Graham G. Giovannucci, Edward Horn-Ross, Pamela L. Leitzmann, Michael Marshall, James R. Mannisto, Satu McCullough, Marjorie L. Miller, Anthony B. Parker, Alexander S. Pietinen, Pirjo Rodriguez, Carmen Rohan, Thomas E. Schatzkin, Arthur Schouten, Leo J. Willett, Walter C. Wolk, Alicja Zhang, Shumin M. Smith-Warner, Stephanie A. TI Intakes of coffee, tea, milk, soda and juice and renal cell cancer in a pooled analysis of 13 prospective studies SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE renal cell cancer; coffee; tea; milk; juice; soda; prospective study ID TYPE-2 DIABETES-MELLITUS; RISK-FACTORS; ALCOHOL-CONSUMPTION; KIDNEY CANCER; UNITED-STATES; DIETARY QUESTIONNAIRE; POSTMENOPAUSAL WOMEN; INSULIN SENSITIVITY; REGRESSION-MODELS; COLORECTAL-CANCER AB Specific beverage intake may be associated with the risk of renal cell cancer through a diluting effect of carcinogens, alterations of hormone levels, or other changes in the renal tubular environment, but few prospective studies have examined these associations. We evaluated the associations between coffee, tea, milk, soda and fruit and vegetable juice intakes and renal cell cancer risk in a pooled analysis of 13 prospective studies (530,469 women and 244,483 men). Participants completed a validated food-frequency questionnaire at baseline. Using the primary data, the study-specific relative risks (RRs) were calculated and then pooled using a random effects model. A total of 1,478 incident renal cell cancer cases were identified during a follow-up of 7-20 years across studies. Coffee consumption was associated with a modestly lower risk of renal cell cancer (pooled multivariate RR for 3 or more 8 oz (237 ml) cups/day versus less than one 8 oz (237 ml) cup/day = 0.84; 95% CI = 0.67-1.05; p value, test for trend = 0.22). Tea consumption was also inversely associated with renal cell cancer risk (pooled multivariate RR for 1 or more 8 oz (237 ml) cups/day versus nondrinkers = 0.85; 95% CI = 0.71-1.02; p value, test for trend = 0.04). No clear associations were observed for milk, soda or juice. Our findings provide strong evidence that neither coffee nor tea consumption increases renal cell cancer risk. Instead, greater consumption of coffee and tea may be associated with a lower risk of renal cell cancer. (c) 2007 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Karolinska Inst, Natl Inst Environm Med, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Univ So Calif, Dept Prevent Med, Los Angeles, CA USA. Univ So Calif, USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. Maastricht Univ, NUTRIM, Dept Epidemiol, Maastricht, Netherlands. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY USA. No Calif Canc Ctr, Fremont, CA USA. NCI, NIH, Natl Publ Hlth Inst, Dept Hlth Promot & Chrron Dis Prevent, Bethesda, MD 20892 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Univ Toronto, Fac Med, Dept Publ Hlth Sci, Toronto, ON, Canada. Mayo Clin, Coll Med, Dept Urol, Jacksonville, FL 32224 USA. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. RP Lee, JE (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM jung.lee@channing.harvard.edu RI Schouten, Leo/G-3713-2012; OI Mannisto, Satu/0000-0002-8668-3046; Lee, Jung Eun/0000-0003-1141-878X; English, Dallas/0000-0001-7828-8188 FU NCI NIH HHS [R01 CA077398] NR 71 TC 22 Z9 22 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2007 VL 121 IS 10 BP 2246 EP 2253 DI 10.1002/ijc.22909 PG 8 WC Oncology SC Oncology GA 221RN UT WOS:000250245100017 PM 17583573 ER PT J AU Turesson, I Linet, MS Bjorkholm, M Kristinsson, SY Goldin, LR Caporaso, NE Landgren, O AF Turesson, Ingemar Linet, Martha S. Bjorkholm, Magnus Kristinsson, Sigurdur Y. Goldin, Lynn R. Caporaso, Neil E. Landgren, Ola TI Ascertainment and diagnostic accuracy for hematopoietic lymphoproliferative malignancies in Sweden 1964-2003 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE diagnostic accuracy; ascertainment; non-Hodgkin lymphoma; Hodgkin lymphoma; multiple myeloma; chronic lymphocytic leukemia; Waldenstrom's macroglobulinemia; lymphoproliferative malignancies ID CHRONIC LYMPHOCYTIC-LEUKEMIA; POPULATION-BASED COHORT; FAMILY-CANCER DATABASE; HODGKIN-LYMPHOMA; BREAST-CANCER; MULTIPLE-MYELOMA; NORDIC COUNTRIES; INCIDENCE RATES; RISK; CLASSIFICATION AB Population-based cancer registries are widely used to provide key information about cancer incidence, survival, determinants of progression and clues about pathogenesis. To substantially expand the limited data on diagnostic accuracy and completeness for lym-phoproliferative (LP) tumors in such databases, we conducted a retrospective investigation of close to 1,000 cases diagnosed during 4 decades in Sweden. We identified and reviewed medical records for 494 LP tumor patients reported to the population-based Swedish Cancer registry and 503 LP tumor patients identified from hospitals in Sweden among patients with LP tumors diagnosed during 1964-2003. The stratified samples were randomly selected from patients according to LP subtype, over 4 equal calendar periods, and among 6 selected hospitals of diverse size and from different geographic regions. We found 97.9% of reported LP tumor cases to fulfill current diagnostic criteria for having an LP tumor and observed 89.7% to have accurate LP tumor subtype. The overall completeness of non-Hodgkin lymphoma, Hodgkin lymphoma and multiple myeloma cases in the Cancer registry was 95-99% but was lower for the more indolent tumors, chronic lymphocytic leukemia (87.9%) and Waldenstrom's macroglobulinemia (68.1%). We observed increased overall under-ascertamment for patients diagnosed above age 80 (27%) and among individuals diagnosed before 1973 (12%). In conclusion the diagnostic accuracy and completeness for classically defined LP tumor entities in the Swedish Cancer registry is high. However, we found under-ascertainment of patients with indolent LP tumors, particularly among patients diagnosed at older ages, with early-stage disease and diagnosed in earlier years. (c) 2007 Wiley-Liss, Inc. C1 Lund Univ, Malmo Univ Hosp, Dept Med, Sect Hematol, SE-20502 Malmo, Sweden. NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Karolinska Inst, Div Med Hematol Ctr, Stockholm, Sweden. Univ Hosp, Stockholm, Sweden. RP Turesson, I (reprint author), Lund Univ, Malmo Univ Hosp, Dept Med, Sect Hematol, SE-20502 Malmo, Sweden. EM ingemar.turesson@med.lu.se RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 FU Intramural NIH HHS NR 36 TC 61 Z9 61 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2007 VL 121 IS 10 BP 2260 EP 2266 DI 10.1002/ijc.22912 PG 7 WC Oncology SC Oncology GA 221RN UT WOS:000250245100019 PM 17583571 ER PT J AU Weiss, JM Huang, WY Rinaldi, S Fears, TR Chatterjee, N Chia, D Crawford, ED Kaaks, R Hayes, RB AF Weiss, Jocelyn M. Huang, Wen-Yi Rinaldi, Sabina Fears, Thomas R. Chatterjee, Nilanjan Chia, David Crawford, E. David Kaaks, Rudolf Hayes, Richard B. TI IGF-1 and IGFBP-3: Risk of prostate cancer among men in the prostate, lung, colorectal and ovarian cancer screening trial SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE prostate; cancer; insulin-like growth factors ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-3; BODY-MASS INDEX; FACTOR AXIS; LIFE-STYLE; CELL-PROLIFERATION; CIRCULATING LEVELS; FACTOR (IGF)-1; UNITED-STATES; WEIGHT CHANGE AB IGF-1 and IGFBP-3 may influence risk of prostate cancer through their roles in cellular growth, metabolism and apoptosis, however, epidemiologic results have been inconsistent. The role of obesity in prostate cancer risk is not clearly understood, but hyperinsulinemia-related increases in bioactive IGF-1 levels, associated with obesity, could be a component of the relationship between the IGF-axis and prostate cancer. We conducted a nested case-control study in the prospective Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to examine associations between IGF-1 and IGFBP-3 and risk of prostate cancer. A total of 727 incident prostate cancer cases and 887 matched controls were selected for this analysis. There was no clear overall association between IGF-1, IGFBP-3 and IGF-1:IGFBP-3 molar ratio (IGFmr) and prostate cancer risk, however, IGFmr was associated with risk in obese men (BMI > 30, p-trend = 0.04), with a greater than 2-fold increased risk in the highest IGFmr quartile (OR 2.34, 95% CI 1.10-5.01). Risk was specifically increased for aggressive disease in obese men (OR 2.80, 95% CI 1.11-7.08). In summary, our large prospective study showed no overall association between the insulin-like growth factor axis and prostate cancer risk, however, IGFmr was related to risk for aggressive prostate cancer in obese men. (c) 2007 Wiley-Liss, Inc. C1 NCI, NIH, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Int Agcy Res Canc, Lyon, France. Univ Calif Los Angeles, Immunogenet Ctr, Los Angeles, CA USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Weiss, JM (reprint author), NCI, NIH, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8123,MSC 7240, Bethesda, MD 20892 USA. EM weissjoc@mail.nih.gov OI Hayes, Richard/0000-0002-0918-661X NR 72 TC 35 Z9 42 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2007 VL 121 IS 10 BP 2267 EP 2273 DI 10.1002/ijc.22921 PG 7 WC Oncology SC Oncology GA 221RN UT WOS:000250245100020 PM 17597108 ER PT J AU Siluk, D Mager, DE Gronich, N Abernethy, D Wainer, IW AF Siluk, Danuta Mager, Donald E. Gronich, Naomi Abernethy, Darrell Wainer, Irving W. TI HPLC-atmospheric pressure chemical ionization mass spectrometric method for enantioselective determination of R,S-propranolol and R,S-hyoscyamine in human plasma SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE atropine; propranolol; Chirobiotic V chiral stationary phase; LC-APCI-MS ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CHIRAL STATIONARY-PHASE; HEART-RATE-VARIABILITY; BETA-BLOCKERS; HUMAN-SERUM; PROPRANOLOL ENANTIOMERS; BIOLOGICAL-FLUIDS; ATROPINE; EXTRACTION; QUANTIFICATION AB A method for the simultaneous determination of R- and S-propranolol and R- and S-hyoscyamine in human plasma was developed, validated and applied to the analysis of samples from a clinical study. Sample preparation was performed by solid-phase extraction of 2ml of human plasma using Oasis MCX cartridges and the enantioselective separations were achieved using a Chirobiotic V chiral stationary phase. The chromatography was carried out using gradient elution with a mobile phase composed of methanol:acetic acid: triethylamine which was varied from 100:0.05:0.04 to 100:0.05:0.1 (v/v/v) over 30 min and delivered at a flow rate I ml/min. The internal standard was R,S-propranolol-d(7) and the analytes were quantified using a single quadrupole mass spectrometer employing APCI interface operated in the positive ion mode with single ion monitoring. The enantioselective separation factors, alpha, were 1.15 and 1.07 for S- and R-propranolol and R- and S-hyoscyamine, respectively. The standard curves were linear for all target compounds With coefficients of determination (r(2)) ranging from 0.9977 to 0.9999. The intra- and inter-day precision and accuracy were <= 13.2% and <= 10.2%, respectively. The assay was used to analyze plasma samples from seven subjects who had received i.v. infusions of R,S-propranolol and R,S-hyoscyarnine. The initial data indicate that R-propranolol was eliminated faster than S-propranolol (CL/f = 2.34 +/- 0.13 L/kg min vs. 2.07 +/- 0.22 L/kg min) and that R-propranolol had a larger volume of distribution at steady-state (V(ss)If= 705 +/- 165 L/kg vs. 589 +/- 130 L/kg). In the case of R,S-hyoscyamine, S-hyoscyamine was eliminated faster than R-hyoscyamine (CL/f = 0.0537 +/- 0.0073 L/kg min vs. 0.0439 +/- 0.0086 L/kg min), while the volumes of distribution at steady-state were similar for the hyoscyamine enantiomers (V(ss)If = 7.82 +/- 2.66 L/kg vs. 7.73 +/- 1.39 L/kg). Published by Elsevier B.V. C1 NIA, Gerontol Res Ctr, NIH, Clin Invest Lab, Baltimore, MD 21224 USA. Med Univ Gdansk, Dept Biopharmaceut & Pharmacodynam, Gdansk, Poland. SUNY Buffalo, Dept Pharmaceut Sci, Buffalo, NY 14260 USA. RP Siluk, D (reprint author), NIA, Gerontol Res Ctr, NIH, Clin Invest Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM silukd@mail.nih.gov FU Intramural NIH HHS NR 42 TC 24 Z9 27 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD NOV 15 PY 2007 VL 859 IS 2 BP 213 EP 221 DI 10.1016/j.jchromb.2007.09.035 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 237VU UT WOS:000251405300009 PM 17951120 ER PT J AU Kimura, T Perry, J Anzai, N Pritchard, JB Moaddel, R AF Kimura, T. Perry, J. Anzai, N. Pritchard, J. B. Moaddel, R. TI Development and characterization of immobilized human organic anion transporter-based liquid chromatographic stationary phase: hOAT1 and hOAT2 SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE hOAT1; hOAT2; drug transporters; affinity chromatography ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CATION TRANSPORTERS; MOLECULAR-CLONING; KIDNEY; MEDIATE; FAMILY; EXPRESSION; CIDOFOVIR; TOXICITY; ADEFOVIR AB This paper reports the development of liquid chromatographic columns containing immobilized organic anion transporters (hOAT1 and hOAT2). Cellular membrane fragments from MDCK cells expressing hOAT1 and S2 cells expressing hOAT2 were immobilized on the surface of the immobilized artificial membrane (IAM) liquid chromatographic stationary phase. The resulting stationary phases were characterized by frontal affinity chromatography, using the marker ligand [H-3]-adefovir for the hOAT1 and [C-14]-p-aminohippurate for the hOAT2 in the presence of multiple displacers. The determined binding affinities (K-d) for eight OAT1 ligands and eight OAT2 ligands were correlated with literature values and a statistically significant correlation was obtained for both the hOAT1 and hOAT2 columns: r(2) = 0.688 (p < 0.05) and r(2) = 0.9967 (p < 0.0001), respectively. The results indicate that the OAT1 and OAT2 have been successfully immobilized with retention of their binding activity. The use of these columns to identify ligands to the respective transporters will be presented. Published by Elsevier B.V. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. Kyorin Univ, Sch Med, Dept Pharmacol & Toxicol, Tokyo 1818611, Japan. RP Moaddel, R (reprint author), NIA, Gerontol Res Ctr, NIH, Bioanalyt & Drug Discovery Unit, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moaddelru@grc.nia.nih.gov FU Intramural NIH HHS [Z99 AG999999, Z01 ES048014-08, Z99 ES999999] NR 27 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD NOV 15 PY 2007 VL 859 IS 2 BP 267 EP 271 DI 10.1016/j.jchromb.2007.09.039 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 237VU UT WOS:000251405300017 PM 17977807 ER PT J AU Kramer, JM Hanel, W Shen, F Isik, N Malone, JP Maitra, A Sigurdson, W Swart, D Tocker, J Jin, T Gaffen, SL AF Kramer, Jill M. Hanel, Walter Shen, Fang Isik, Nilgun Malone, James P. Maitra, Amarnath Sigurdson, Wade Swart, David Tocker, Joel Jin, Tian Gaffen, Sarah L. TI Cutting edge: Identification of a pre-ligand assembly domain (PLAD) and ligand binding site in the IL-17 receptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ERYTHROPOIETIN RECEPTOR; SIGNAL-TRANSDUCTION; INTERLEUKIN-17; CYTOKINES; TARGET; OLIGOMERIZATION; INFLAMMATION; SUPERFAMILY; INHIBITION; ACTIVATION AB IL-17 is the hallmark cytokine of the newly described "Th17" lymphocyte population. The composition, subunit dynamics, and ligand contacts of the IL-17 receptor are poorly defined. We previously demonstrated that the IL-17RA subunit oligomerizes in the membrane without a ligand, In this study, computational modeling identified two fibronectin-III-like (FN) domains in IL-17RA connected by a nonstructured linker, which we predicted to mediate homotypic interactions. In yeast two-hybrid, 'proximal FN domain (FN2), but not the membrane the membrane-distal domain (FNI), formed homomeri. c interactions. The ability of FN2 to drive ligand-independent multimerization was verified by coimmunoprecipitation and fluorescence resonance energy no transfer microscopy. Thus, FN2 constitutes a "pre-ligand assembly domain" (PLAD). Further studies indicated that the FN2 linker domain contains the IL-17 binding site, which was never mapped. However, the FNI domain is also required for high affinity interactions with IL-17. Therefore, although the PLAD is located entirely within FN2, effective ligand binding also involves contributions from the linker and FN1. C1 SUNY Buffalo, Dept Oral Biol, Buffalo, NY 14214 USA. SUNY Buffalo, Dept Microbiol & Immunol, Buffalo, NY 14214 USA. SUNY Buffalo, Confocal Facil, Buffalo, NY 14214 USA. Amgen Inc, Dept Inflammat Res, Seattle, WA 98119 USA. NIAID, Immunogenet Lab, Rockville, MD 20852 USA. RP Gaffen, SL (reprint author), 3435 Main St, Buffalo, NY 14214 USA. EM sgaffen@buffalo.edu RI Gaffen, Sarah/B-1560-2009; OI Kramer, Jill/0000-0001-9828-8556 FU Intramural NIH HHS; NIAID NIH HHS [AI49329, R01 AI049329, R21 AI049329]; NIAMS NIH HHS [AR05048]; NIDCR NIH HHS [DE07034, DE14831, F30 DE014831, F30 DE014831-04, T32 DE007034] NR 33 TC 30 Z9 31 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2007 VL 179 IS 10 BP 6379 EP 6383 PG 5 WC Immunology SC Immunology GA 229HA UT WOS:000250792700001 PM 17982023 ER PT J AU Ramaswamy, M Dumont, C Cruz, AC Muppidi, JR Gomez, TS Billadeau, DD Tybulewicz, VLJ Siegel, RM AF Ramaswamy, Madhu Dumont, Celine Cruz, Anthony C. Muppidi, Jagan R. Gomez, Timothy S. Billadeau, Daniel D. Tybulewicz, Victor L. J. Siegel, Richard M. TI Cutting edge: Rac GTPases sensitize activated T Cells to die via Fas SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; IMMUNOLOGICAL SYNAPSE; ACTIN POLYMERIZATION; APOPTOSIS; DEFICIENCY; MUTATIONS; DEATH; CD44; CD95 AB Inactivated CD4(+) T cells, TCR restimulation triggers apoptosis that depends on interactions between the death receptor Fas and its ligand, FasL. This process, termed restimulation-induced cell death (RICD), is a mechanism of peripheral immune tolerance. TCR signaling sensitizes activated T cells to Fas-mediated apoptosis, but what pathways mediate this process are not known. In this study we identify the Rho GTTases Rac1 and Rac2 as essential components in restimulation-induced cell death. RNA interference-mediated knockdown of Rac GTPases greatly reduced Fas-dependent, TCR-induced apoptosis. The ability of Rac1 to sensitize T cells to Tas-induced apoptosis correlated with Rac-mediated cytoskeletal reorganization, dephosphorylation of the ERM (ezrin/radixin/moesin) family of cytoskeletal linker proteins, and the translocation of Fas to lipid raft microdomains. In primary activated CD4+ T cells, Rac1 and Rac2 were independently required for maximal TCR-induced apoptosis. Activating Rac signaling may be a novel way to sensitize chronically stimulated lymphocytes to Fas induced apoptosis, an important goal in the treatment of autoimmune diseases. C1 NIAMSD, Immunoregulat Unit, Autoimmun Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. Natl Inst Med Res, Div Immune Cell Biol, London NW7 1AA, England. Mayo Clin, Dept Oncol Res, Rochester, MN 55905 USA. RP Siegel, RM (reprint author), Bldg 10,Room 9N238, Bethesda, MD 20892 USA. EM rsiegel@nih.gov RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 FU Intramural NIH HHS; Medical Research Council [MC_U117527252] NR 20 TC 29 Z9 30 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2007 VL 179 IS 10 BP 6384 EP 6388 PG 5 WC Immunology SC Immunology GA 229HA UT WOS:000250792700002 PM 17982024 ER PT J AU Khodoun, M Lewis, C Yang, JQ Orekov, T Potter, C Wynn, T Mentink-Kane, M Hershey, GKK Wills-Karp, M Finkelman, FD AF Khodoun, Marat Lewis, Christina Yang, Jun-Qi Orekov, Tatyana Potter, Crystal Wynn, Thomas Mentink-Kane, Margaret Hershey, Gurjit K. Khurana Wills-Karp, Marsha Finkelman, Fred D. TI Differences in expression, affinity, and function of soluble (s)IL-4R alpha and sIL-13R alpha 2 suggest opposite effects on allergic responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IL-4 RECEPTOR-ALPHA; COMMON GAMMA-CHAIN; IN-VIVO; PROTECTIVE IMMUNITY; INTERLEUKIN-13 RECEPTOR; SIGNALING PATHWAYS; BINDING SUBUNIT; SPLEEN-CELLS; MAST-CELLS; T-CELLS AB IL-4 and IL-13 are each bound by soluble receptors (sRs) that block their activity. Both of these sRs (sIL-4R alpha and sIL-13R alpha 2) are present in low nanogram per milliliter concentrations in the serum from unstimulated mice, but differences in affinity and half-life suggest differences in function. Serum IL-4/sIL-4R alpha complexes rapidly dissociate, releasing active IL-4, whereas sIL13R alpha 2 and IL-13 form a stable complex that has a considerably longer half-life than uncomplexed IL-13, sIL-13R alpha 2, IL-4, or sIL-4R alpha. Approximately 25% of sIL-13R alpha 2 in serum is complexed to IL-13; this percentage and the absolute quantity of sIL13Ra2 in serum increase considerably during a Th2 response. sIL-13Ra2 gene expression is up-regulated by both IL-4 and IL-13; the effect of IL-4 is totally IL-4R alpha-dependent while the effect of IL-13 is partially IL-4R alpha-independent. Inhalation of an IL-13/sIL-13R alpha 2 complex does not affect the expression of IL-13-inducible genes but increases the expression of two genes, Vnn1 and Pira-1, whose products activate APCs and promote neutrophilic inflammation. These observations suggest that sIL-4R alpha predominantly sustains, increases, and diffuses the effects of IL-4, whereas sIL-13Ra2 limits the direct effects of IL-13 to the site of IL-13 production and forms a stable complex with IL-13 that may modify the quality and intensity of an allergic inflammatory response. C1 Cincinnati Vet Affairs Med Ctr, Cincinnati, OH 45220 USA. Univ Cincinnati, Coll Med, Dept Med, Cincinnati, OH 45267 USA. Cincinnati Childrens Hosp, Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA. Cincinnati Childrens Hosp, Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA. NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Finkelman, FD (reprint author), Cincinnati Vet Author, Med Ctr, 3200 Vine St, Cincinnati, OH 45220 USA. EM ffinkelman@pol.net FU NHLBI NIH HHS [HL076383]; NIAID NIH HHS [R01 AI052099, R01 AI55848, R01AI58157] NR 73 TC 31 Z9 33 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2007 VL 179 IS 10 BP 6429 EP 6438 PG 10 WC Immunology SC Immunology GA 229HA UT WOS:000250792700009 PM 17982031 ER PT J AU Swindle, EJ Coleman, JW Deleo, FR Metcalfe, DD AF Swindle, Emily J. Coleman, John W. Deleo, Frank R. Metcalfe, Dean D. TI Fc epsilon RI- and Fc gamma receptor-mediated production of reactive oxygen species by mast cells is lipoxygenase- and cyclooxygenase-dependent and NADPH oxidase-independent SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; PROSTAGLANDIN-H SYNTHASE; HYDROGEN-PEROXIDE; ARACHIDONIC-ACID; PHOSPHOLIPASE A(2); TYROSINE PHOSPHORYLATION; 5-LIPOXYGENASE PATHWAY; PERITONEAL-MACROPHAGES; SUPEROXIDE GENERATION; CHEMOKINE PRODUCTION AB We investigated the enzymes responsible for Fc epsilon RI-dependent production of reactive oxygen species (ROS) and the influence of ROS on mast cell secretory responses. 5-Lipoxygenase (5-LO) was the primary enzyme involved in ROS production by human mast cells (huMC) and mouse bone marrow-derived mast cells (mBMMC) following Fc epsilon RI aggregation because incubation with 5-LO inhibitors (AA861, nordihydroguaiaretic acid, zileuton) but not a flavoenzyme inhibitor (diphenyleneiodonium) completely abrogated Ag-induced dichlorodihydrofluorescein (DCF) fluorescence. Furthermore, 5-LO-deficient mBMMC had greatly reduced Fc epsilon RI-dependent DCF fluorescence compared with wild type mBMMC or those lacking a functional NADPH oxidase (i.e., gp91(phox)- or p47(phox)-deficient cells). A minor role for cyclooxygenase (COX)-1 in Fe epsilon RI-dependent ROS production was demonstrated by inhibition of Ag-mediated DCF fluorescence by a COX-1 inhibitor (FR122047) and reduced DCF fluorescence in COX-1-deficient mBMMC. Complete abrogation of Fc epsilon RI-dependent ROS production in mast cells had no effect on degranulation or cytokine secretion. In response to the NADPH oxidase-stimulating agents including PMA, mBMMC and huMC produced negligible ROS. IgG-coated latex beads did stimulate ROS production in huMC, and in this experiment 5-LO and COX again appeared to be the enzymatic sources of ROS. In contrast, IgG-coated latex bead-induced ROS production in human polymorphonuclear leukocytes occurred by the NADPH oxidase pathway. Thus mBMMC and huMC generate ROS by 5-LO and COX-1 in response to Fc epsilon RI aggregation; huMC generate ROS upon exposure to IgG-coated latex beads by 5-LO and COX; and ROS appear to have no significant role in Fc epsilon RI-dependent degranulation and cytokine production. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Swindle, EJ (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C 209,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. EM ejswindle@niaid.nih.gov FU Intramural NIH HHS NR 70 TC 28 Z9 30 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2007 VL 179 IS 10 BP 7059 EP 7071 PG 13 WC Immunology SC Immunology GA 229HA UT WOS:000250792700075 PM 17982097 ER PT J AU Hildesheim, A Herrero, R AF Hildesheim, Allan Herrero, Rolando TI Human papillomavirus vaccine should be given before sexual debut for maximum benefit SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID QUADRIVALENT VACCINE C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fdn INCIENSA, San Jose, Costa Rica. RP Hildesheim, A (reprint author), NCI, NIH, Div Canc Epidemiol, 6120 Execut Blvd,Rm 7062, Rockville, MD 20852 USA. EM hildesha@epndce.nci.nih.gov NR 5 TC 25 Z9 25 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 IS 10 BP 1431 EP 1432 DI 10.1086/522869 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 231BP UT WOS:000250921800001 PM 18008218 ER PT J AU Bausch, DG Feldmann, H Geisbert, TW Bray, M Sprecher, AG Boumandouki, P Rollin, PE Roth, C AF Bausch, Daniel G. Feldmann, Heinz Geisbert, Thomas W. Bray, Mike Sprecher, A. G. Boumandouki, Paul Rollin, Pierre E. Roth, Cathy CA Winnipeg Filovirus Clin Work Grp TI Outbreaks of filovirus hemorrhagic fever: Time to refocus on the patient SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Recent Advances and Future Challenges in Filovirus Research CY SEP, 2006 CL Winnipeg, CANADA ID EBOLA-VIRUS INFECTION; ATTENUATED RECOMBINANT VACCINE; NONHUMAN-PRIMATES; POSTEXPOSURE PROTECTION; EFFICACY; CONGO; LIVE AB In the 40 years since the recognition of filoviruses as agents of lethal human disease, there have been no specific advances in antiviral therapies or vaccines and few clinical studies on the efficacy of supportive care. On 20 September 2006, experts from 14 countries representing 68 institutions integrally involved in the response to outbreaks of filovirus hemorrhagic fever gathered at the National Microbiology Laboratory of the Public Health Agency of Canada in Winnipeg to discuss possible remedies for this grim situation, in a unique workshop entitled "Marburg and Ebola Hemorrhagic Fever: Feasibility of Prophylaxis and Therapy." A summary of the opportunities for and challenges to improving treatment of filovirus hemorrhagic fevers is presented here. C1 Tulane Sch Publ Hlth & Trop Med, Dept Trop Med, New Orleans, LA 70112 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. Med Sans Frontieres, Brussels, Belgium. Minist Hlth Populat, Brazzaville, Congo. WHO, CH-1211 Geneva, Switzerland. RP Bausch, DG (reprint author), Tulane Sch Publ Hlth & Trop Med, Dept Trop Med, 1430 Tulane Ave, New Orleans, LA 70112 USA. EM dbausch@tulane.edu NR 27 TC 31 Z9 33 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S136 EP S141 DI 10.1086/520542 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400004 PM 17940941 ER PT J AU Bradfute, SB Braun, DR Shamblin, JD Geisbert, JB Paragas, J Garrison, A Hensley, LE Geisbert, TW AF Bradfute, Steven B. Braun, Denise R. Shamblin, Joshua D. Geisbert, Joan B. Paragas, Jason Garrison, Aura Hensley, Lisa E. Geisbert, Thomas W. TI Lymphocyte death in a mouse model of Ebola virus infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Recent Advances and Future Challenges in Filovirus Research CY SEP, 2006 CL Winnipeg, CANADA ID HEMORRHAGIC-FEVER; GUINEA-PIGS; CELL-DEATH; CYNOMOLGUS MACAQUES; MARBURG VIRUSES; T-LYMPHOCYTES; ZAIRE VIRUS; APOPTOSIS; PATHOGENESIS; SEPSIS AB Background. A striking feature of Zaire Ebola virus (ZEBOV) infection in nonhuman primates is the rapid depletion of T and NK lymphocytes by apoptosis. In a mouse model of ZEBOV infection, lymphocyte death is a prominent finding; however, the mechanism of death and the lymphocyte subsets that are targeted remain unknown. Methods. We extended the characterization of lymphocyte death in a mouse model of ZEBOV infection by evaluating lymphocytes during the course of disease, using flow cytometry, electron microscopy, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL). Results. B cell, CD4+ and CD8+ T cell, and NK cell counts all dropped dramatically in the blood of infected BALB/c mice, and lymphocyte death was observed in the spleen by means of TUNEL staining and in the blood by means of electron microscopy. Morphologically, lymphocyte death occurred by both classic apoptosis and apoptosis-like programmed cell death. Conclusions. The early and severe loss of peripheral blood NK and CD8+ lymphocytes in ZEBOV-infected mice is similar to that seen in macaques. The morphological basis of lymphocyte death in ZEBOV-infected mice appears to be both classic apoptosis and apoptosis-like programmed cell death, although lymphocyte apoptosis in ZEBOV-infected nonhuman primates seems to occur primarily via classic apoptosis. The mouse model of ZEBOV infection may be useful for the screening of therapeutics directed against limiting lymphocyte death. C1 NIH, NIAID, Integrated Res Facil, Ft Detrick, MD USA. NIAID, Div Intramural Res, Bethesda, MD 20892 USA. RP Geisbert, TW (reprint author), Boston Univ, Sch Med, Dept Microbiol, 715 Albany St, Boston, MA 02118 USA. EM geisbert@bu.edu NR 35 TC 42 Z9 44 U1 0 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S296 EP S304 DI 10.1086/520602 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400027 PM 17940964 ER PT J AU Bray, M Murphy, FA AF Bray, Mike Murphy, Frederick A. TI Filovirus research: Knowledge expands to meet a growing threat SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID EBOLA HEMORRHAGIC-FEVER; POSTEXPOSURE PROTECTION; DENDRITIC CELLS; VIRUS-INFECTION; MARBURG; PATHOGENESIS; APOPTOSIS; CONGO; REPLICATION; RESERVOIRS C1 NIH, NIAID, Integrated Res Facil, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77550 USA. RP Bray, M (reprint author), NIH, NIAID, 6700A Rockledge Dr,Rm 5128, Bethesda, MD 20892 USA. EM mbray@niaid.nih.gov NR 54 TC 23 Z9 25 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S438 EP S443 DI 10.1086/520552 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400044 PM 17940981 ER PT J AU Ebihara, H Theriault, S Neumann, G Alimonti, JB Geisbert, JB Hensley, LE Groseth, A Jones, SM Geisbert, TW Kawaoka, Y Feldmann, H AF Ebihara, Hideki Theriault, Steven Neumann, Gabriele Alimonti, Judie B. Geisbert, Joan B. Hensley, Lisa E. Groseth, Allison Jones, Steven M. Geisbert, Thomas W. Kawaoka, Yoshihiro Feldmann, Heinz TI In vitro and in vivo characterization of recombinant Ebola viruses expressing enhanced green fluorescent protein SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Recent Advances and Future Challenges in Filovirus Research CY SEP, 2006 CL Winnipeg, CANADA ID MARBURG-VIRUS; GUINEA-PIGS; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; FOREIGN GENE; CELL-CULTURE; ZAIRE VIRUS; INFECTION; REPLICATION; PATHOGENESIS AB To facilitate an understanding of the molecular aspects of the pathogenesis of Zaire ebolavirus (ZEBOV) infection, we generated 2 different recombinant viruses expressing enhanced green fluorescent protein (eGFP) from additional transcription units inserted at different positions in the virus genome. These viruses showed in vitro phenotypes similar to that of wild-type ZEBOV (wt-ZEBOV) and were stable over multiple passages. Infection with one of the viruses expressing eGFP produced only mild disease in rhesus macaques, demonstrating a marked attenuation in this animal model. However, in mice lacking signal transducer and activator of transcription 1, both viruses expressing eGFP caused lethal cases of disease that were moderately attenuated, compared with that caused by wt-ZEBOV. In mice, viral replication could be easily tracked by the detection of eGFP-positive cells in tissues, by use of flow cytometry. These findings demonstrate that the incorporation of a foreign gene will attenuate ZEBOV in vivo but that these viruses still have potential for in vitro and in vivo research applications. C1 Univ Tokyo, Int Res Ctr Infect Dis, Dept Special Pathogens, Tokyo, Japan. Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Virol, Tokyo, Japan. Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Tokyo, Saitama, Japan. Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada. Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. NIH, NIAID, Integrated Res Facil, Ft Detrick, MD USA. RP Feldmann, H (reprint author), Publ Hlth Agcy Canada, 1015 Arlington St, Winnipeg, MB R3E 3R2, Canada. EM Hideki_Ebihara@phac-aspc.gc.ca FU NIAID NIH HHS [1-U54-AI-057153] NR 45 TC 38 Z9 38 U1 1 U2 9 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S313 EP S322 DI 10.1086/520590 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400029 PM 17940966 ER PT J AU Feldmann, H Geisbert, T Kawaoka, Y Johnson, KM AF Feldmann, Heinz Geisbert, Thomas Kawaoka, Yoshihiro Johnson, Karl M. TI Dedication: Jim Orzechowski (1944-2003) and Michael Kiley (1942-2004) SO JOURNAL OF INFECTIOUS DISEASES LA English DT Biographical-Item C1 Canadian Sci Ctr Human & Anim Hlth, Winnipeg, MB A3E 3R2, Canada. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. NIAID, NIH, Integrated Res Facil Ft Detrick, Ft Detrick, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA. Univ Tokyo, Dept Microbiol & Immunol, Div Virol, Tokyo, Japan. Univ Tokyo, Int Res Ctr Infect Dis, Inst Med Sci, Tokyo, Japan. Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Saitama, Japan. RP Feldmann, H (reprint author), Canadian Sci Ctr Human & Anim Hlth, 1015 Arlington St, Winnipeg, MB A3E 3R2, Canada. EM Heinz_Feldmann@phac-aspc.gc.ca NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S127 EP S128 DI 10.1086/520539 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400001 ER PT J AU Feldmann, H Geisbert, T Kawaoka, Y AF Feldmann, Heinz Geisbert, Thomas Kawaoka, Yoshihiro TI Filoviruses: Recent advances and future challenges SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material C1 Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. NIH, Natl Inst All & Infect Dis, Integrated Res Facil, Ft Detrick, MD USA. Univ Hlth Sci, Uniformed Serv, Bethesda, MD USA. Univ Wisconsin, Madison, WI USA. Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Tokyo, Japan. Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Tokyo, Saitama, Japan. RP Geisbert, T (reprint author), Boston Univ, Sch Med, Dept Microbiol, 715 Albany St,R514, Boston, MA 02118 USA. EM geisbert@bu.edu NR 0 TC 7 Z9 7 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S129 EP S130 DI 10.1086/520550 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400002 PM 17940939 ER PT J AU Geisbert, TW Daddario-DiCaprio, KM Geisbert, JB Young, HA Formenty, P Fritz, EA Larsen, T Hensley, LE AF Geisbert, Thomas W. Daddario-DiCaprio, Kathleen M. Geisbert, Joan B. Young, Howard A. Formenty, Pierre Fritz, Elizabeth A. Larsen, Tom Hensley, Lisa E. TI Marburg virus Angola infection of rhesus macaques: Pathogenesis and treatment with recombinant nematode anticoagulant protein c2 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Recent Advances and Future Challenges in Filovirus Research CY SEP, 2006 CL Winnipeg, CANADA ID EBOLA HEMORRHAGIC-FEVER; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; TISSUE FACTOR/FACTOR VIIA; AMINO-ACID CHANGES; NONHUMAN-PRIMATES; CYNOMOLGUS MACAQUES; MACROPHAGE TROPISM; AGENT DISEASE; MONKEYS; COAGULATION AB Background. The procoagulant tissue factor (TF) is thought to play a role in the coagulation disorders that characterize filoviral infections. In this study, we evaluated the pathogenesis of lethal infection with the Angola strain of Marburg virus (MARV-Ang) in rhesus macaques and tested the efficacy of recombinant nematode anticoagulant protein c2 (rNAPc2), an inhibitor of TF/factor VIIa, as a potential treatment. Methods. Twelve rhesus macaques were challenged with a high dose (1000 pfu) of MARV-Ang. Six macaques were treated with rNAPc2, and 6 macaques served as control animals. Results. All 6 control animals succumbed to MARV-Ang challenge by day 8 (mean, 7.3 days), whereas 5 of 6 rNAPc2-treated animals died on day 9 and 1 rNAPc2-treated animal survived. The disease course for MARV-Ang infection appeared to progress more rapidly in rhesus macaques than has been previously reported for other strains of MARV. In contrast to Ebola virus (EBOV) infection in macaques, up-regulation of TF was not as striking, and deposition of fibrin was a less prominent pathologic feature of disease in these animals. Conclusions. These data show that the pathogenicity of MARV-Ang infection appears to be consistent with the apparent increased human virulence attributed to this strain. The apparent reduced efficacy of rNAPc2 against MARV-Ang infection, compared with its efficacy against EBOV infection, appears to be associated with differences in TF induction and fibrin deposition. C1 NIH, NIAID, Integrated Res Facil, Ft Detrick, MD USA. USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. USA, Med Res Inst Infect Dis, Div Pathol, Ft Detrick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NCI, Ctr Canc Res, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD 21701 USA. WHO, Dept Communicable Dis Surveillance & Response, CH-1211 Geneva, Switzerland. RP Geisbert, TW (reprint author), Boston Univ, Sch Med, Dept Microbiol, 715 Albany St,R514, Boston, MA 02118 USA. EM geisbert@bu.edu NR 42 TC 71 Z9 74 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S372 EP S381 DI 10.1086/520608 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400036 PM 17940973 ER PT J AU Hensley, LE Stevens, EL Yan, SB Geisbert, JB Macias, WL Larsen, T Daddario-DiCaprio, KM Cassell, GH Jahrling, PB Geisbert, TW AF Hensley, Lisa E. Stevens, Edward L. Yan, S. Betty Geisbert, Joan B. Macias, William L. Larsen, Tom Daddario-DiCaprio, Kathleen M. Cassell, Gail H. Jahrling, Peter B. Geisbert, Thomas W. TI Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Recent Advances and Future Challenges in Filovirus Research CY SEP, 2006 CL Winnipeg, CANADA ID SEVERE SEPSIS; VIRUS INFECTION; ANTICOAGULANT PATHWAY; NONHUMAN-PRIMATES; UNITED-STATES; SEPTIC SHOCK; PROTECTION; RESPONSES; ALPHA; EPIDEMIOLOGY AB Background. Infection of primates with Zaire ebolavirus (ZEBOV) leads to hypotension, coagulation disorders, and an impaired immune response and, in many ways, resembles severe sepsis. Rapid decreases in plasma levels of protein C are a prominent feature of severe sepsis and ZEBOV hemorrhagic fever (ZHF). Currently, recombinant human activated protein C (rhAPC [Xigris; Eli Lilly]) is licensed for treating human patients with severe sepsis who are at high risk of death. The aim of this study was to test the efficacy of rhAPC as a potential treatment for ZHF. Methods. Fourteen rhesus macaques were challenged with a uniformly lethal dose of ZEBOV; 11 of these monkeys were treated by intravenous infusion with rhAPC beginning 30-60 min after challenge and continuing for 7 days. Three control monkeys received sterile saline in parallel. Results. All 3 control monkeys died on day 8, whereas 2 of the 11 rhAPC-treated monkeys survived. The mean time to death for the rhAPC-treated monkeys that did not survive ZEBOV challenge was 12.6 days. The difference in survival was significant when the rhAPC-treated monkeys were compared with historical controls. Conclusions. The experimental findings provide evidence that ZHF and severe sepsis share underlying mechanisms and may respond to the same therapies. C1 USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. USA, Med Res Inst Infect Dis, Div Pathol, Ft Detrick, MD 21702 USA. NIH, NIAID, Integrated Res Facil, Ft Detrick, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Lilly Res Labs, Indianapolis, IN USA. RP Geisbert, TW (reprint author), Boston Univ, Sch Med, Dept Microbiol, 715 Albany St, Boston, MA 02118 USA. EM geisbert@bu.edu NR 48 TC 83 Z9 93 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S390 EP S399 DI 10.1086/520598 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400038 PM 17940975 ER PT J AU Jahrling, PB Geisbert, JB Swearengen, JR Larsen, T Geisbert, TW AF Jahrling, Peter B. Geisbert, Joan B. Swearengen, James R. Larsen, Thomas Geisbert, Thomas W. TI Ebola hemorrhagic fever: Evaluation of passive immunotherapy in nonhuman primates SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Recent Advances and Future Challenges in Filovirus Research CY SEP, 2006 CL Winnipeg, CANADA ID VIRUS-INFECTION AB The survival of 7 of 8 patients with Ebola virus (EBOV) infection after transfusions of convalescent-phase blood during a 1995 outbreak of EBOV infection is frequently cited as evidence that passive immunotherapy is a viable treatment option. To test whether whole-blood transfusions were more efficacious than passively administered immunoglobulins or monoclonal antibodies, we transfused convalescent-phase blood from EBOV-immune monkeys into naive animals shortly after challenge with EBOV. Although passively acquired antibody titers comparable to those associated with effective vaccination were obtained, all monkeys that had received transfusions succumbed to infection concurrently with control monkeys. These data cast further doubt on the value of passive immunotherapy for the treatment of EBOV infection. C1 NIH, NIAID, Integrated Res Facil, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. USA, Med Res Inst Infect Dis, Div Pathol, Ft Detrick, MD 21702 USA. Associat Assessment & Accreditat Lab Anim Care I, Rockville, MD USA. RP Jahrling, PB (reprint author), NIH, NIAID, Integrated Res Facil, Bldg 10, Bethesda, MD 20892 USA. EM jahrlingp@niaid.nih.gov NR 16 TC 54 Z9 58 U1 0 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S400 EP S403 DI 10.1086/520587 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400039 PM 17940976 ER PT J AU Jones, SM Stroeher, U Fernando, L Qiu, XG Alimonti, J Melito, P Bray, M Klenk, HD Feldmann, H AF Jones, Steven M. Stroeher, Ute Fernando, Lisa Qiu, Xianggou Alimonti, Judie Melito, Pasquale Bray, Mike Klenk, Hans-Dieter Feldmann, Heinz TI Assessment of a vesicular stomatitis virus-based vaccine by use of the mouse model of Ebola virus hemorrhagic fever SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Recent Advances and Future Challenges in Filovirus Research CY SEP, 2006 CL Winnipeg, CANADA ID ATTENUATED RECOMBINANT VACCINE; NONHUMAN-PRIMATES; RHESUS-MONKEYS; EXPERIMENTAL-INFECTION; REPLICATION-COMPETENT; IMMUNE-RESPONSES; PASSIVE TRANSFER; MARBURG VIRUS; GENE-TRANSFER; ZAIRE VIRUS AB Background. In humans and nonhuman primates, Ebola virus causes a virulent viral hemorrhagic fever for which no licensed vaccines or therapeutic drugs exist. In the present study, we used the mouse model for Ebola hemorrhagic fever to assess the safety and efficacy of a vaccine based on a live attenuated vesicular stomatitis virus expressing the Zaire ebolavirus (ZEBOV) glycoprotein. Methods. Healthy mice were given the vaccine in various doses, decreasing from 2 X 10(4) to 2 plaque-forming units (pfu), with both systemic and mucosal vaccination routes used. Mice were challenged with to 10(3) to 10(6) lethal doses of mouse-adapted ZEBOV. Severely immunocompromised mice were injected with 2 X 10(5) pfu, which is 10 times greater than the immunization dose normally used, to test vaccine safety. Results. Two plaque-forming units of the vaccine protected against lethal challenge, and mucosal immunization was found to be as protective as systemic injection. The replicating vaccine was never detected in the immunized animals, nor were there clinical signs after immunization. Immunization of severely immunocompromised mice with 200,000 pfu of vaccine resulted in no clinical symptoms. Conclusions. Our data suggest that the vaccine is highly potent and safe and that it very rapidly induces "sterile" immunity in mice. The potential for mucosal delivery, if confirmed in nonhuman primates, makes it an excellent candidate for mass immunization during outbreaks or in the event of intentional release. C1 Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada. Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. NIH, Biodef Clin Res Branch, Bethesda, MD 20892 USA. Univ Marburg, Inst Virol, D-3550 Marburg, Germany. RP Jones, SM (reprint author), 1015 Arlington St, Winnipeg, MB R3E 3R2, Canada. EM Steven_jones@phac-aspc.gc.ca NR 48 TC 49 Z9 51 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S404 EP S412 DI 10.1086/520591 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400040 PM 17940977 ER PT J AU Larsen, T Stevens, EL Davis, KJ Geisbert, JB Daddario-DiCaprio, KM Jahrling, PB Hensley, LE Geisbert, TW AF Larsen, Thomas Stevens, Edward L. Davis, Kelly J. Geisbert, Joan B. Daddario-DiCaprio, Kathleen M. Jahrling, Peter B. Hensley, Lisa E. Geisbert, Thomas W. TI Pathologic findings associated with delayed death in nonhuman primates experimentally infected with Zaire Ebola virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Recent Advances and Future Challenges in Filovirus Research CY SEP, 2006 CL Winnipeg, CANADA ID HEMORRHAGIC-FEVER; MONKEYS; CONGO AB Zaire Ebola virus infection in macaques causes a fatal disease with a pathogenesis similar to that in humans. During several independent therapy studies, we noted altered tissue tropism in 6 rhesus macaques that survived longer than those with a typical disease course. The mean time to death for these 6 macaques was 21.7 days, which is significantly longer than the average mean time to death of 8.3 days for 20 untreated historical control animals. In addition to living significantly longer, these 6 animals exhibited a variety of deteriorating clinical signs with pathologic findings that were not seen in the untreated control animals, as well as the presence of viral antigen in the brain, eye, pancreas, thyroid, and lung. We suggest that treatment extended the time course of the disease and permitted the virus to infect tissues not usually affected in the typical model. C1 USA, Med Res Inst Infect Dis, Div Pathol, Ft Detrick, MD 21702 USA. USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. NIH, NIAID, Integrated Res Facil, Ft Detrick, MD USA. RP Geisbert, TW (reprint author), Boston Univ, Sch Med, Dept Microbiol, 715 Albany St, Boston, MA 02118 USA. EM geisbert@bu.edu NR 16 TC 23 Z9 24 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S323 EP S328 DI 10.1086/520589 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400030 PM 17940967 ER PT J AU Takada, A Ebihara, H Feldmann, H Geisbert, TW Kawaoka, Y AF Takada, Ayato Ebihara, Hideki Feldmann, Heinz Geisbert, Thomas W. Kawaoka, Yoshihiro TI Epitopes required for antibody-dependent enhancement of Ebola virus infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Recent Advances and Future Challenges in Filovirus Research CY SEP, 2006 CL Winnipeg, CANADA ID CELL-LINES; GLYCOPROTEIN; ENTRY; IDENTIFICATION; PARTICLES; RECEPTORS; PRIMATES; VACCINE; C1Q; GP AB We have shown that antibody-dependent enhancement (ADE) of infection with Zaire Ebola virus (ZEBOV) is mediated by interaction of virus-specific antibodies with Fc receptors or complement component C1q and its receptors in vitro. ADE activities of the antisera to the viral glycoprotein (GP) were virus species specific and were primarily correlated with immunoglobulin (Ig) G2a and IgM levels but not with IgG1 levels. Interestingly, compared with ZEBOV, Reston Ebola virus (REBOV) had substantially weaker potential to induce ADE antibodies. Using monoclonal antibodies, we identified ZEBOV-specific ADE epitopes. To confirm epitope specificity, we constructed a chimeric ZEBOV GP, the ADE epitopes of which were replaced with the corresponding regions of REBOV GP. We found that mouse antisera to the chimeric ZEBOV GP showed less potential to induce ADE activity than did mouse antisera to wild-type ZEBOV GP, although they retained neutralizing activity. These data suggest that GP lacking the ADE-inducing epitopes may increase the potential of GP as a vaccine antigen. C1 Hokkaido Univ, Dept Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido 0600818, Japan. Univ Tokyo, Div Virol, Dept Microbiol & Immunol, Tokyo, Japan. Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Tokyo, Japan. Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Tokyo, Saitama, Japan. Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. NIH, NIAID, Integrated Res Facil, Ft Detrick, MD USA. Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA. RP Takada, A (reprint author), Hokkaido Univ, Dept Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido 0600818, Japan. EM atakada@czc.hokudai.ac.jp RI Takada, Ayato/A-6679-2012 NR 30 TC 33 Z9 35 U1 0 U2 17 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S347 EP S356 DI 10.1086/520581 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400033 PM 17940970 ER PT J AU Warfield, KL Posten, NA Swenson, DL Olinger, GG Esposito, D Gillette, WK Hopkins, RF Costantino, J Panchal, RG Hartley, JL Aman, MJ Bavari, S AF Warfield, Kelly L. Posten, Nichole A. Swenson, Dana L. Olinger, Gene G. Esposito, Dominic Gillette, William K. Hopkins, Ralph F. Costantino, Julie Panchal, Rekha G. Hartley, James L. Aman, M. Javad Bavari, Sina TI Filovirus-like particles produced in insect cells: Immunogenicity and protection in rodents SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Recent Advances and Future Challenges in Filovirus Research CY SEP, 2006 CL Winnipeg, CANADA ID VIRUS-LIKE PARTICLES; EBOLA-VIRUS; MARBURG-VIRUS; DENDRITIC CELLS; MATRIX PROTEIN; GUINEA-PIGS; BACULOVIRUS VECTORS; VACCINES; GLYCOPROTEIN; VP40 AB Background. Virus-like particles (VLPs) of Ebola virus (EBOV) and Marburg virus (MARV) produced in human 293T embryonic kidney cells have been shown to be effective vaccines against filoviral infection. In this study, we explored alternative strategies for production of filovirus-like particle-based vaccines, to accelerate the development process. The goal of this work was to increase the yield of VLPs, while retaining their immunogenic properties. Methods. Ebola and Marburg VLPs (eVLPs and mVLPs, respectively) were generated by use of recombinant baculovirus constructs expressing glycoprotein, VP40 matrix protein, and nucleoprotein from coinfected insect cells. The baculovirus-derived eVLPs and mVLPs were characterized biochemically, and then the immune responses produced by the eVLPs in insect cells were studied further. Results. The baculovirus-derived eVLPs elicited maturation of human myeloid dendritic cells (DCs), indicating their immunogenic properties. Mice vaccinated with insect cell-derived eVLPs generated antibody and cellular responses equivalent to those vaccinated with mammalian 293T cell-derived eVLPs and were protected from EBOV challenge in a dose-dependent manner. Conclusion. Together, these data suggest that filovirus-like particles produced by baculovirus expression systems, which are amenable to large-scale production, are highly immunogenic and are suitable as safe and effective vaccines for the prevention of filoviral infection. C1 USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. NCI, Sci Applicat Int Corp, Prot Express Lab, Frederick, MD 21701 USA. NCI, Sci Applicat Int Corp, Target Struct Based Drug Discovery Grp, Frederick, MD 21701 USA. RP Bavari, S (reprint author), USA, Med Res Inst Infect Dis, 1425 Porter St, Ft Detrick, MD 21702 USA. EM kelly.warfield@us.army.mil; sina.bavari@us.army.mil OI Olinger, Gene/0000-0001-7338-0292 FU NCI NIH HHS [N01-CO-12400] NR 40 TC 39 Z9 42 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S421 EP S429 DI 10.1086/520612 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400042 PM 17940979 ER PT J AU Warfield, KL Swenson, DL Olinger, GG Kalina, WV Viard, M Aitichou, M Chi, X Ibrahim, S Blumenthal, R Raviv, Y Bavari, S Aman, MJ AF Warfield, Kelly L. Swenson, Dana L. Olinger, Gene G. Kalina, Warren V. Viard, Mathias Aitichou, Mohamed Chi, Xiaoli Ibrahim, Sofi Blumenthal, Robert Raviv, Yossef Bavari, Sina Aman, M. Javad TI Ebola virus inactivation with preservation of antigenic and structural integrity by a photoinducible alkylating agent SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Recent Advances and Future Challenges in Filovirus Research CY SEP, 2006 CL Winnipeg, CANADA ID PROTECT GUINEA-PIGS; HEMORRHAGIC-FEVER; BIOLOGICAL-MEMBRANES; NONHUMAN-PRIMATES; POLIOVIRUS VACCINATION; MONOCLONAL-ANTIBODIES; PARTICLES PROTECT; CUTTER INCIDENT; UNITED-STATES; INFECTION AB Current methods for inactivating filoviruses are limited to high doses of irradiation or formalin treatment, which may cause structural perturbations that are reflected by poor immunogenicity. In this report, we describe a novel inactivation technique for Zaire Ebola virus (ZEBOV) that uses the photoinduced alkylating probe 1,5-iodonaphthylazide (INA). INA is incorporated into lipid bilayers and, when activated by ultraviolet irradiation, alkylates the proteins therein. INA treatment of ZEBOV resulted in the complete loss of infectivity in cells. Results of electron microscopy and virus-capture assays suggested the preservation of conformational surface epitopes. Challenge with 50,000 pfu of INA-inactivated, mouse-adapted ZEBOV did not cause disease or death in mice. A single vaccination with INA-inactivated ZEBOV (equivalent to 5 X 10(4)pfu) protected mice against lethal challenge with 1000 pfu of ZEBOV. INA- inactivated virus induced a protective response in 100% of mice when administered 3 days before challenge. Thus, INA may have significant potential for the development of vaccines and immunotherapeutics for filoviruses and other enveloped viruses. C1 Integrat BioTherapeut Inc, Frederick, MD 21704 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD USA. NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. NCI, Sci Appl Int Corp, Basic Program, Frederick, MD 21701 USA. RP Aman, MJ (reprint author), Integrat BioTherapeut Inc, 4539 Metropolitan Ct, Frederick, MD 21704 USA. EM javad@integratedbiotherapeutics.com OI Olinger, Gene/0000-0001-7338-0292 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 41 TC 30 Z9 31 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2007 VL 196 SU 2 BP S276 EP S283 DI 10.1086/520605 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233KS UT WOS:000251090400024 PM 17940961 ER PT J AU Hariprakasha, HK Kosakowska-Cholody, T Meyer, C Cholody, WM Stinson, SF Tarasova, NI Michejda, CJ AF Hariprakasha, Humcha K. Kosakowska-Cholody, Teresa Meyer, Colin Cholody, Wieslaw M. Stinson, Sherman F. Tarasova, Nadya I. Michejda, Christopher. J. TI Optimization of naphthalimide-imidazoacridone with potent antitumor activity leading to clinical candidate (HKH40A, RTA 502) SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BISIMIDAZOACRIDONES; CANCERS; AGENT AB Unsymmetrical bifunctional antitumor agent WMC79 was further optimized to generate compound 7b that not only inhibited the growth of many tumor cell lines, but caused rapid apoptosis. Unlike the parent compound, 7b is toxic to both p53 positive and negative cancer cells. It. has potent in vivo activity against xenografts of human colon and pancreatic tumors in athymic mice. C1 NCI, Ctr Canc Res, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Frederick, MD 21702 USA. Reata Pharmaceut, Irving, TX USA. RP Tarasova, NI (reprint author), NCI, Ctr Canc Res, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21702 USA. EM tarasova@ncifcrf.gov FU Intramural NIH HHS NR 9 TC 15 Z9 15 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 15 PY 2007 VL 50 IS 23 BP 5557 EP 5560 DI 10.1021/jm7009777 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 229MY UT WOS:000250809300007 PM 17939651 ER PT J AU Zhou, M Shen, D Head, JE Chew, EY Chevez-Barrios, P Green, WR Chan, CC AF Zhou, Min Shen, Defen Head, James E. Chew, Emily Y. Chevez-Barrios, Patricia Green, W. Richard Chan, Chi-Chao TI Ocular clusterin expression in von Hippel-Lindau disease SO MOLECULAR VISION LA English DT Article ID TUMOR-SUPPRESSOR GENE; RENAL-CELL CARCINOMA; VHL GENE; ANGIOMATOSIS RETINAE; CLINICAL-FEATURES; PROTEIN; CANCER; HEMANGIOBLASTOMA; IDENTIFICATION; CYTOTOXICITY AB Purpose: Clusterin is a multifunctional glycoprotein. Its mRNA is ubiquitously expressed, with high levels in von Hippel-Lindau (VHL) target organs such as the brain, liver, kidney, and adrenal medulla. Decreased clusterin secretion has been reported in renal cell carcinoma associated with VHL disease. The purpose of this study was to investigate ocular clusterin expression in VHL disease. Methods: This retrospective case series included nine eyes with retinal hemangioblastoma/hemangioma associated with VHL disease, one eye from a patient with a history of VHL disease and central nervous system hemangioblastomas but without ocular lesions, one surgically-excised optic nerve with optic nerve hemangioblastoma/hemangioma, and three normal control eyes. Ocular specimens were evaluated by routine histology, immunohistochemistry for clusterin expression, and molecular detection of clusterin transcripts within ocular VHL hemangioblastomas compared with normal tissue from the same eye using microdissection and quantitative real-time PCR. Results: All retinal hemangioblastoma were composed of typical VHL tumor cells admixed with small vascular channels as well as glial cells. Marked decrease of clusterin immunoreactivity was detected in all retinal hemangioblastoma and the optic nerve hemangioblastoma, whereas positive clusterin reactivity of the vascular and glial components was similar to that of normal retina. Quantitative real-time PCR analysis confirmed the decrease of clusterin mRNA in the VHL associated retinal hemangioblastoma and optic nerve hemangioblastoma in five cases. Conclusions: Clusterin shows possible important functions in tumor suppression by the VHL gene product (pVHL) and the potential to be a novel biomarker in retinal hemangioblastoma associated VHL disease. Further investigation of clusterin may provide better understanding of retinal hemangioblastoma associated with VHL disease. C1 [Zhou, Min; Shen, Defen; Head, James E.; Chew, Emily Y.; Chan, Chi-Chao] NEI, NIH, Bethesda, MD 20892 USA. [Zhou, Min] Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, Shanghai 200433, Peoples R China. [Chevez-Barrios, Patricia] Methodist Hosp, Dept Pathol, Ophthalm Pathol Program, Houston, TX 77030 USA. [Green, W. Richard] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. RP Chan, CC (reprint author), NEI, NIH, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22, Z99 EY999999] NR 47 TC 4 Z9 6 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD NOV 15 PY 2007 VL 13 IS 239-41 BP 2129 EP 2136 PG 8 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 310QT UT WOS:000256545800003 PM 18079682 ER PT J AU Alabi, AA Bahamonde, MI Jung, HJ Il Kim, J Swartz, KJ AF Alabi, AbdulRasheed A. Bahamonde, Maria Isabel Jung, Hoi Jong Il Kim, Jae Swartz, Kenton J. TI Portability of paddle motif function and pharmacology in voltage sensors SO NATURE LA English DT Article ID DEPENDENT K+ CHANNEL; GATED ION CHANNELS; POTASSIUM CHANNEL; GATING-CHARGE; TOXIN RECEPTOR; LIPID-MEMBRANE; KVAP; HANATOXIN; MODIFIER; INHIBITOR AB Voltage-sensing domains enable membrane proteins to sense and react to changes in membrane voltage. Although identifiable S1-S4 voltage-sensing domains are found in an array of conventional ion channels and in other membrane proteins that lack pore domains, the extent to which their voltage-sensing mechanisms are conserved is unknown. Here we show that the voltage-sensor paddle, a motif composed of S3b and S4 helices, can drive channel opening with membrane depolarization when transplanted from an archaebacterial voltage-activated potassium channel (KvAP) or voltage-sensing domain proteins (Hv1 and Ci-VSP) into eukaryotic voltage-activated potassium channels. Tarantula toxins that partition into membranes can interact with these paddle motifs at the protein-lipid interface and similarly perturb voltage-sensor activation in both ion channels and proteins with a voltage-sensing domain. Our results show that paddle motifs are modular, that their functions are conserved in voltage sensors, and that they move in the relatively unconstrained environment of the lipid membrane. The widespread targeting of voltage-sensor paddles by toxins demonstrates that this modular structural motif is an important pharmacological target. C1 NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. EM swartzk@ninds.nih.gov FU Intramural NIH HHS [ZIA NS002945-13] NR 49 TC 143 Z9 145 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 15 PY 2007 VL 450 IS 7168 BP 370 EP U2 DI 10.1038/nature06266 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 231AM UT WOS:000250918600044 PM 18004375 ER PT J AU Luo, Q Mitchell, D Jones, M Mondillo, K Vythilingam, M Blair, RJR AF Luo, Qian Mitchell, Derek Jones, Matthew Mondillo, Krystal Vythilingam, Meena Blair, R. James R. TI Common regions of dorsal anterior cingulate and cortices provide attentional control of distracters emotionality and visibility SO NEUROIMAGE LA English DT Article DE attention; emotion; visibility; top-down attentional control; fMRI ID EVENT-RELATED FMRI; POSTTRAUMATIC-STRESS-DISORDER; SELECTIVE ATTENTION; FACIAL EXPRESSIONS; NEURAL MECHANISMS; VISUAL-ATTENTION; HUMAN AMYGDALA; COGNITIVE CONTROL; COUNTING STROOP; CORTEX AB Top-down attentional control is necessary to ensure successful task performance in the presence of distracters. Lateral prefrontal cortex, parietal cortex and anterior cingulate cortex have been previously implicated in top-down attentional control. However, it is unclear whether these regions are engaged independent of distracter type or whether, as has been suggested for anterior cingulate cortex, different regions provide attentional control over emotional versus other forms of salient distracter. In the current task, subjects viewed targets that were preceded by distracters that varied in both emotionality and visibility. We found that behaviorally, the presence of preceding distracters significantly interfered with target judgment. At the neural level, increases in the emotional and visual saliency of distracters were both associated with increased activity in proximal regions of prefrontal, parietal and cingulate cortex. Moreover, a conjunction analysis indicated considerable overlap in the regions of prefrontal, parietal cortex and anterior cingulate cortex responding to distracters of increased emotionality and visibility. (c) 2007 Elsevier Inc. All rights reserved. C1 NIMH, Mood & Anxiety Disorders Program, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Luo, Q (reprint author), NIMH, Mood & Anxiety Disorders Program, Natl Inst Hlth, 15K N Dr,Room 300C,MSC 2670, Bethesda, MD 20892 USA. EM luoj@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 83 TC 23 Z9 26 U1 7 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2007 VL 38 IS 3 BP 631 EP 639 DI 10.1016/j.neuroimage.2007.07.051 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 224FF UT WOS:000250432200022 PM 17889565 ER PT J AU Jonker, DJ O'Callaghan, CJ Karapetis, CS Zalcberg, JR Tu, DS Au, HJ Berry, SR Krahn, M Price, T Simes, RJ Tebbutt, NC van Hazel, G Wierzbicki, R Langer, C Moore, MJ AF Jonker, Derek J. O'Callaghan, Chris J. Karapetis, Christos S. Zalcberg, John R. Tu, Dongsheng Au, Heather-Jane Berry, Scott R. Krahn, Marianne Price, Timothy Simes, R. John Tebbutt, Niall C. van Hazel, Guy Wierzbicki, Rafal Langer, Christiane Moore, Malcolm J. TI Cetuximab for the treatment of colorectal cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GROWTH-FACTOR RECEPTOR; PHASE-II TRIAL; RANDOMIZED-TRIAL; FLUOROURACIL FAILURE; SUPPORTIVE CARE; PLUS IRINOTECAN; LEUCOVORIN; THERAPY; OXALIPLATIN AB Background: Cetuximab, an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor (EGFR), has activity against colorectal cancers that express EGFR. Methods: From December 2003 to August 2005, 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine, irinotecan, and oxaliplatin or had contraindications to treatment with these drugs underwent randomization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care (287 patients) or best supportive care alone (285 patients). The primary end point was overall survival. Results: In comparison with best supportive care alone, cetuximab treatment was associated with a significant improvement in overall survival (hazard ratio for death, 0.77; 95% confidence interval [CI], 0.64 to 0.92; P=0.005) and in progression-free survival (hazard ratio for disease progression or death, 0.68; 95% CI, 0.57 to 0.80; P<0.001). These benefits were robust after adjustment in a multivariable Cox proportional-hazards model. The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone. Partial responses occurred in 23 patients (8.0%) in the cetuximab group but in none in the group assigned to supportive care alone (P<0.001); the disease was stable in an additional 31.4% of patients assigned to cetuximab and in 10.9% of patients assigned to supportive care alone (P<0.001). Quality of life was better preserved in the cetuximab group, with less deterioration in physical function and global health status scores (both P<0.05). Cetuximab treatment was associated with a characteristic rash; a rash of grade 2 or higher was strongly associated with improved survival (hazard ratio for death, 0.33; 95% CI, 0.22 to 0.50; P<0.001). The incidence of any adverse event of grade 3 or higher was 78.5% in the cetuximab group and 59.1% in the group assigned to supportive care alone (P<0.001). Conclusions: Cetuximab improves overall survival and progression-free survival and preserves quality-of-life measures in patients with colorectal cancer in whom other treatments have failed. (ClinicalTrials.gov number, NCT00079066.). C1 Univ Ottawa, Ottawa Hosp Res Inst, Ottawa, ON, Canada. Queens Univ, NCI, Inst Canada Clin Trials Grp, Kingston, ON, Canada. Flinders Med Ctr, Adelaide, SA, Australia. Univ Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Univ Melbourne, Dept Med, Melbourne, Vic, Australia. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. St Boniface Gen Hosp, Winnipeg, MB R2H 2A6, Canada. Queen Elizabeth Hosp, Adelaide, SA, Australia. Univ Sydney, Natl Hlth & Med Res Council Clin Trials Ctr, Sydney, NSW 2006, Australia. Austin Hlth, Melbourne, Vic, Australia. Sir Charles Gairdner Hosp, Perth, WA, Australia. Lakeridge Hlth, Oshawa, ON, Canada. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. RP Jonker, DJ (reprint author), Univ Ottawa, Ottawa Hosp Reg Canc Ctr, 501 Smyth Rd,Box 912, Ottawa, ON K1H 8L6, Canada. EM djonker@ottawahospital.on.ca RI Price, Timothy/G-1404-2012; Simes, Robert/P-1497-2014 OI Price, Timothy/0000-0002-3922-2693; NR 29 TC 1053 Z9 1093 U1 9 U2 64 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 15 PY 2007 VL 357 IS 20 BP 2040 EP 2048 DI 10.1056/NEJMoa071834 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 230RV UT WOS:000250894500006 PM 18003960 ER PT J AU Pogribny, IP Bagnyukova, TV Tryndyak, VP Muskhelisbvili, L Rodriguez-Juarez, R Kovalchuk, O Han, T Fuscoe, JC Ross, SA Beland, FA AF Pogribny, Igor P. Bagnyukova, Tetyana V. Tryndyak, Volodymyr P. Muskhelisbvili, Levan Rodriguez-Juarez, Rocio Kovalchuk, Olga Han, Tao Fuscoe, James C. Ross, Sharon A. Beland, Frederick A. TI Gene expression profiling reveals underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE tamoxifen; rat; hepatocarcinogenesis; gene expression ID HUMAN HEPATOCELLULAR-CARCINOMA; HEPATIC STELLATE CELLS; DNA ADDUCT FORMATION; GROWTH-FACTOR; NONALCOHOLIC STEATOHEPATITIS; LIVER FIBROSIS; METABOLIZING-ENZYMES; TRANSGENIC MICE; ANGIOTENSIN-II; PDGF-B AB Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce nonalcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the molecular mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. In the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during early stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that early stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during early stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G, to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt 1/2, Akt3, and cyclin B, D1, and D3 proteins. The early appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen. Published by Elsevier Inc. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 59 TC 15 Z9 16 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2007 VL 225 IS 1 BP 61 EP 69 DI 10.1016/j.taap.2007.07.001 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 230AH UT WOS:000250847200005 PM 17706260 ER PT J AU Gonzales, DA Norsworthy, KJ Kern, SJ Banks, S Sieving, PC Star, RA Natanson, C Danner, RL AF Gonzales, Denise A. Norsworthy, Kelly J. Kern, Steven J. Banks, Steve Sieving, Pamela C. Star, Robert A. Natanson, Charles Danner, Robert L. TI A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity SO BMC MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; RADIOCONTRAST-INDUCED NEPHROPATHY; ACUTE-RENAL-FAILURE; AGENT-ASSOCIATED NEPHROTOXICITY; PERCUTANEOUS CORONARY INTERVENTION; HIGH-RISK PATIENTS; RADIOGRAPHIC-CONTRAST; CARDIAC-CATHETERIZATION; CLINICAL-TRIALS; ORAL ACETYLCYSTEINE AB Background: Meta-analyses of N-acetylcysteine (NAC) for preventing contrast-induced nephrotoxicity (CIN) have led to disparate conclusions. Here we examine and attempt to resolve the heterogeneity evident among these trials. Methods: Two reviewers independently extracted and graded the data. Limiting studies to randomized, controlled trials with adequate outcome data yielded 22 reports with 2746 patients. Results: Significant heterogeneity was detected among these trials (I(2) = 37%; p = 0.04). Meta-regression analysis failed to identify significant sources of heterogeneity. A modified L'Abbe plot that substituted groupwise changes in serum creatinine for nephrotoxicity rates, followed by model-based, unsupervised clustering resolved trials into two distinct, significantly different ( p < 0.0001) and homogeneous populations ( I(2) = 0 and p > 0.5, for both). Cluster I studies ( n = 18; 2445 patients) showed no benefit ( relative risk ( RR) = 0.87; 95% confidence interval ( CI) 0.68 - 1.12, p = 0.28), while cluster 2 studies ( n = 4; 301 patients) indicated that NAC was highly beneficial ( RR = 0.15; 95% CI 0.07 - 0.33, p < 0.0001). Benefit in cluster 2 was unexpectedly associated with NAC-induced decreases in creatinine from baseline ( p = 0.07). Cluster 2 studies were relatively early, small and of lower quality compared with cluster I studies ( p = 0.01 for the three factors combined). Dialysis use across all studies ( five control, eight treatment; p = 0.42) did not suggest that NAC is beneficial. Conclusion: This meta-analysis does not support the efficacy of NAC to prevent CIN. C1 [Gonzales, Denise A.; Norsworthy, Kelly J.; Kern, Steven J.; Banks, Steve; Natanson, Charles; Danner, Robert L.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. [Sieving, Pamela C.] NIH, Natl Inst Hlth Lib, Bethesda, MD 20892 USA. [Star, Robert A.] NIH, Div Kidney Urol & Hematol Dis, NIDDK, Bethesda, MD 20892 USA. RP Gonzales, DA (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bldg 10, Bethesda, MD 20892 USA. EM dgonzales@cc.nih.gov; kelly.norsworthy@gmail.com; kernsj@cc.nih.gov; kernsj@cc.nih.gov; sievingp@nih.gov; starr@nih.gov; cnatanson@cc.nih.gov; rdanner@nih.gov OI Sieving, Pamela/0000-0003-3794-5000 FU Intramural NIH HHS NR 111 TC 79 Z9 81 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD NOV 14 PY 2007 VL 5 AR 32 DI 10.1186/1741-7015-5-32 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 251XO UT WOS:000252409600001 PM 18001477 ER PT J AU Grakalic, I Panlilio, LV Thorridike, EB Schindler, CW AF Grakalic, Ivana Panlilio, Leigh V. Thorridike, Eric B. Schindler, Charles W. TI Differential involvement of dopamine receptors in conditioned suppression induced by cocaine SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE conditioned suppression; cocaine; SCH 23390; eticlopride; BP 897; food; (rat) ID NUCLEUS-ACCUMBENS SHELL; ANTAGONIST SCH 23390; FEAR-POTENTIATED STARTLE; PLACE PREFERENCE; D-3 RECEPTOR; SEEKING BEHAVIOR; TASTE-AVERSION; UNCONDITIONED STIMULUS; LOCOMOTOR-ACTIVITY; RATS AB Cocaine-paired stimuli can suppress food-reinforced operant behavior in rats, providing an animal model of conditioned drug effects. To study the neuropharmacological basis of this phenomenon, we examined the effects of various dopamine receptor antagonists on the acquisition and expression of cocaine-induced conditioned suppression in rats. Superimposed on an ongoing baseline of food-reinforced operant responding, a stimulus was paired with response-independent cocaine (3.0 mg/kg, i.v.) during each of 8 training sessions. To study acquisition, independent groups of rats were given saline, the dopamine D-1-like receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390) (0.001-0.03 mg/kg, i.p.), or the dopamine D-2-like receptor antagonist eticlopride (0.001-0.03 mg/kg, i.p.) prior to each training session. To study expression, independent groups of rats were trained first, then given saline, SCH 23390, eticlopride, or N-[4-(4-(2-methoxyphenyl)piperazinyl)butyl]-2-naphthamide (BP 897) (a dopamine D-3 partial receptor agonist; 0.1-1.0 mg/kg, i.p.) before test sessions in which the stimulus was presented without cocaine. Pre-treatment with either SCH 23390 or eticlopride during acquisition reduced the direct suppressant effects of cocaine, but conditioning was blocked only in rats that were treated with SCH 23390 during acquisition training. Expression of conditioning was attenuated only by eticlopride. Thus, dopamine at least partially mediates both the acquisition and expression of cocaine-induced conditioned suppression, with activation of dopamine D-1- and D-2-like receptors underlying these respective processes. (c) Published by Elsevier B.V. C1 NIDA, Behav Neurosci Res Branch, Preclin Pharmacol Sect, Intramural Res Program, Baltimore, MD 21224 USA. RP Grakalic, I (reprint author), NIDA, Behav Neurosci Res Branch, Preclin Pharmacol Sect, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM igrakalic@mail.nih.gov FU Intramural NIH HHS [Z99 AA999999] NR 69 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 14 PY 2007 VL 573 IS 1-3 BP 116 EP 123 DI 10.1016/j.ephar.2007.06.037 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 222ID UT WOS:000250288700016 PM 17628537 ER PT J AU Bossert, JM Poles, GC Wihbey, KA Koya, E Shaham, Y AF Bossert, Jennifer M. Poles, Gabriela C. Wihbey, Kristina A. Koya, Eisuke Shaham, Yavin TI Differential effects of blockade of dopamine D-1-family receptors in nucleus Accumbens core or shell on reinstatement of heroin seeking induced by contextual and discrete cues SO JOURNAL OF NEUROSCIENCE LA English DT Article DE conditioned cues; drug abuse; nucleus accumbens; opiates; reinstatement; relapse; SCH 23390 ID COCAINE-SEEKING; DRUG-SEEKING; VENTRAL STRIATUM; PREFRONTAL CORTEX; ANTAGONIST SCH-23390; BASOLATERAL AMYGDALA; PROLONGED ABSTINENCE; OLFACTORY TUBERCLE; INDUCED RELAPSE; FOS EXPRESSION AB In humans, exposure to environmental contexts previously associated with heroin intake can provoke drug relapse, but the neuronal mechanisms mediating this relapse are unknown. Using a drug relapse model, we found previously that reexposing rats to heroin-associated contexts, after extinction of drug-reinforced responding in different contexts, reinstates heroin seeking. This effect is attenuated by inhibition of glutamate transmission in the ventral tegmental area and medial accumbens shell, components of the mesolimbic dopamine system. Here, we explored the role of dopamine of the accumbens in context-induced reinstatement by using the D-1-family receptor antagonist SCH 23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride]. Rats were trained to self-administer heroin for 12 d; drug infusions were paired with a discrete tone-light cue. Subsequently, the heroin-reinforced lever pressing was extinguished in the presence of the discrete cue in a context that differed from the drug self-administration context in terms of visual, auditory, tactile, and circadian cues. When tested in the original drug self-administration context, systemic and medial or lateral accumbens shell SCH 23390 injections attenuated context-induced reinstatement of heroin seeking, whereas accumbens core SCH 23390 injections were ineffective. In contrast, core but not lateral or medial shell SCH 23390 injections attenuated discrete-cue-induced reinstatement in a nondrug context after extinction of lever presses without this cue. Results indicate that activation of medial and lateral accumbens shell D-1-family dopamine receptors mediate context-induced reinstatement of heroin seeking and provide the first demonstration for a role of lateral shell dopamine in conditioned drug effects. Results also demonstrate novel dissociable roles of accumbens core and shell in context-versus discrete-cue-induced reinstatement of heroin seeking. C1 Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, Natl Inst Hlth,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, Natl Inst Hlth,Dept Hlth & Human Serv, 5500 Natham Shock Dr, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI shaham, yavin/G-1306-2014 FU Intramural NIH HHS [Z01 DA000434-08] NR 65 TC 156 Z9 160 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 14 PY 2007 VL 27 IS 46 BP 12655 EP 12663 DI 10.1523/JNEUROSCI.3926-07.2007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 231NA UT WOS:000250952700026 PM 18003845 ER PT J AU Volkow, ND Wang, GJ Telang, F Fowler, JS Logan, J Jayne, M Ma, YM Pradhan, K Wong, C AF Volkow, Nora D. Wang, Gene-Jack Telang, Frank Fowler, Joanna S. Logan, Jean Jayne, Millard Ma, Yeming Pradhan, Kith Wong, Christopher TI Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement SO JOURNAL OF NEUROSCIENCE LA English DT Article DE PET; dopamine; alcohol; orbitofrontal cortex; ventral striatum; reward ID VENTRAL TEGMENTAL AREA; ETHANOL WITHDRAWAL SYNDROME; HUMAN BRAIN; INTRAVENOUS METHYLPHENIDATE; ORAL METHYLPHENIDATE; PREFRONTAL CORTEX; TYPE-2 ALCOHOLICS; NEURONAL-ACTIVITY; COCAINE ABUSERS; DRUG-ADDICTION AB The value of rewards (natural rewards and drugs) is associated with dopamine increases in the nucleus accumbens and varies as a function of context. The prefrontal cortex has been implicated in the context dependency of rewards and in the fixated high value that drugs have in addiction, although the mechanisms are not properly understood. Here we test the hypothesis that the prefrontal cortex regulates the value of rewards by modulating dopamine increases in nucleus accumbens and that this regulation is disrupted in addicted subjects. We used positron emission tomography to evaluate the activity of the prefrontal cortex (measuring brain glucose metabolism with [F-18] fluorodeoxyglucose) and dopamine increases (measured with [C-11] raclopride, a D-2/D-3 receptor ligand with binding that is sensitive to endogenous dopamine) induced by the stimulant drug methylphenidate in 20 controls and 20 detoxified alcoholics, most of whom smoked. In all subjects, methylphenidate significantly increased dopamine in striatum. In ventral striatum (where the nucleus accumbens is located) and in putamen, dopamine increases were associated with the rewarding effects of methylphenidate (drug liking and high) and were profoundly attenuated in alcoholics (70 and 50% lower than controls, respectively). In controls, but not in alcoholics, metabolism in orbitofrontal cortex (region involved with salience attribution) was negatively associated with methylphenidate-induced dopamine increases in ventral striatum. These results are consistent with the hypothesis that the orbitofrontal cortex modulates the value of rewards by regulating the magnitude of dopamine increases in the ventral striatum and that disruption of this regulation may underlie the decreased sensitivity to rewards in addicted subjects. C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. NIAAA, Lab Neuroimaging, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. SUNY Stony Brook, Dept Appl Math, Stony Brook, NY 11794 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov OI Logan, Jean/0000-0002-6993-9994 FU Intramural NIH HHS; NIMH NIH HHS [MH66961-02] NR 55 TC 183 Z9 185 U1 3 U2 8 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 NOV 14 PY 2007 VL 27 IS 46 BP 12700 EP 12706 DI 10.1523/JNEUROSCI.3371-07.2007 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 231NA UT WOS:000250952700031 PM 18003850 ER PT J AU Chigurupati, S Arumugam, TV Son, TG Lathia, JD Jameel, S Mughal, MR Tang, SC Jo, DG Camandola, S Giunta, M Rakova, I McDonnell, N Miele, L Mattson, MP Poosala, S AF Chigurupati, Srinivasulu Arumugam, Thiruma V. Son, Tae Gen Lathia, Justin D. Jameel, Shafaq Mughal, Mohamed R. Tang, Sung-Chun Jo, Dong-Gyu Camandola, Simonetta Giunta, Marialuisa Rakova, Irina McDonnell, Nazli Miele, Lucio Mattson, Mark P. Poosala, Suresh TI Involvement of Notch Signaling in Wound Healing SO PLOS ONE LA English DT Article AB The Notch signaling pathway is critically involved in cell fate decisions during development of many tissues and organs. In the present study we employed in vivo and cell culture models to elucidate the role of Notch signaling in wound healing. The healing of full-thickness dermal wounds was significantly delayed in Notch antisense transgenic mice and in normal mice treated with gamma-secretase inhibitors that block proteolytic cleavage and activation of Notch. In contrast, mice treated with a Notch ligand Jagged peptide showed significantly enhanced wound healing compared to controls. Activation or inhibition of Notch signaling altered the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in a scratch wound healing model in ways consistent with roles for Notch signaling in wound healing functions all three cell types. These results suggest that Notch signaling plays important roles in wound healing and tissue repair, and that targeting the Notch pathway might provide a novel strategy for treatment of wounds and for modulation of angiogenesis in other pathological conditions. C1 [Chigurupati, Srinivasulu; Arumugam, Thiruma V.; Son, Tae Gen; Lathia, Justin D.; Jameel, Shafaq; Mughal, Mohamed R.; Tang, Sung-Chun; Jo, Dong-Gyu; Camandola, Simonetta; Giunta, Marialuisa; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Rakova, Irina; McDonnell, Nazli] NIA, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Chigurupati, Srinivasulu; Poosala, Suresh] NIA, Res Resources Branch, Intramural Res Program, Baltimore, MD 21224 USA. [Arumugam, Thiruma V.] Texas Tech Univ, Hlth Sci Ctr, Dept Pharmaceut Sci, Sch Pharm, Amarillo, TX USA. [Jo, Dong-Gyu] Sungkyunkwan Univ, Coll Pharm, Suwon, South Korea. [Miele, Lucio] Loyola Univ, Dept Pathol, Breast Canc Program, Hlth Sci Ctr, Maywood, IL 60153 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012 FU National Institute on Aging, NIH FX Supported by the Intramural Research Program of the National Institute on Aging, NIH. NR 45 TC 51 Z9 51 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 14 PY 2007 VL 2 IS 11 AR e1167 DI 10.1371/journal.pone.0001167 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JA UT WOS:000207459100009 PM 18000539 ER PT J AU Golin, J Kon, ZN Wu, CP Martello, J Hanson, L Supernavage, S Ambudkar, SV Sauna, ZE AF Golin, John Kon, Zachary N. Wu, Chung-Pu Martello, Justin Hanson, Leanne Supernavage, Sherry Ambudkar, Suresh V. Sauna, Zuben E. TI Complete inhibition of the Pdr5p multidrug efflux pump ATPase activity by its transport substrate clotrimazole suggests that GTP as well as ATP may be used as an energy source SO BIOCHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING DOMAIN; MULTIPLE-DRUG RESISTANCE; P-GLYCOPROTEIN ABCB1; CANDIDA-ALBICANS; SACCHAROMYCES-CEREVISIAE; YEAST; PROTEIN; CDR1P; HYDROLYSIS; MEMBRANE AB The yeast Pdr5p transporter is a 160 kDa protein that effluxes a large variety of xenobiotic compounds. In this study, we characterize its ATPase activity and demonstrate that it has biochemical features reminiscent of those of other ATP-binding cassette multidrug transporters: a relatively high K-m for ATP (1.9 mM), inhibition by orthovanadate, and the ability to specifically bind an azido ATP analogue at the nucleotide-binding domains. Pdr5p-specific ATPase activity shows complete, concentration-dependent inhibition by clotrimazole, which is also known to be a potent transport substrate. Our results indicate, however, that this inhibition is noncompetitive and caused by the interaction of clotrimazole with the transporter at a site that is distinct from the ATP-binding domains. Curiously, Pdr5p-mediated transport of clotrimazole continues at intracellular concentrations of substrate that should eliminate all ATPase activity. Significantly, however, we observed that the Pdr5p has GTPase and UTPase activities that are relatively resistant to clotrimazole. Furthermore, the K,,(GTPase) roughly matches the intracellular concentrations of the nucleotide reported for yeast. Using purified plasma membrane vesicles, we demonstrate that Pdr5p can use GTP to fuel substrate transport. We propose that Pdr5p increases its multidrug transport substrate specificity by using more than one nucleotide as an energy source. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. RP Sauna, ZE (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bldg 37, Bethesda, MD 20892 USA. EM saunaz@mail.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [GM07721] NR 43 TC 26 Z9 27 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 13 PY 2007 VL 46 IS 45 BP 13109 EP 13119 DI 10.1021/bi701414f PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 228XT UT WOS:000250766600022 PM 17956128 ER PT J AU Baxa, U Wickner, RB Steven, AC Anderson, DE Marekov, LN Yau, WM Tycko, R AF Baxa, Ulrich Wickner, Reed B. Steven, Alasdair C. Anderson, D. Eric Marekov, Lyuben N. Yau, Wai-Ming Tycko, Robert TI Characterization of beta-sheet structure in Ure2p(1-89) yeast prion fibrils by solid-state nuclear magnetic resonance SO BIOCHEMISTRY LA English DT Article ID HET-S PRION; AMYLOID FIBRILS; SACCHAROMYCES-CEREVISIAE; NMR-SPECTROSCOPY; EXPERIMENTAL CONSTRAINTS; MOLECULAR-STRUCTURE; CHEMICAL-SHIFTS; POLAR ZIPPERS; PROTEIN URE2P; DOMAINS FORM AB Residues 1-89 constitute the Asn- and Gln-rich segment of the Ure2p protein and produce the [URE3] prion of Saccharomyces cerevisiae by forming the core of intracellular Ure2p amyloid. We report the results of solid-state nuclear magnetic resonance (NMR) measurements that probe the molecular structure of amyloid fibrils formed by Ure2p(1-89), in vitro. Data include measurements of intermolecular magnetic dipole-dipole couplings in samples that are C-13-labeled at specific sites and two-dimensional N-15-C-13 and C-13-C-13 NMR spectra of samples that are uniformly N-15- and C-13-labeled. Intermolecular dipole-dipole couplings indicate that the beta-sheets in Ure2p(1-89) fibrils have an in-register parallel structure. An in-register parallel P-sheet structure permits polar zipper interactions among side chains of Gln and Asn residues and explains the tolerance of [URE3] to scrambling of the sequence in residues 1-89. Two-dimensional NMR spectra of uniformly labeled Ure2p(1-89) fibrils, even when fully hydrated, show NMR linewidths that exceed those in solid-state NMR spectra of fibrils formed by residues 218-289 of the HET-s prion protein of Podospora anserina [as originally reported in Siemer, A. B., Ritter, C., Ernst, M., Rick, R., and Meier, B. H. (2005) Angew. Chem., Int. Ed. 44, 2441-2444 and confirmed by measurements reported here] by factors of three or more, indicating a lower degree of structural order at the molecular level in Ure2p 1 -89 fibrils. The very high degree of structural order in HET-s fibrils indicated by solid-state NMR data is therefore not a universal characteristic of prion proteins, and is likely to be a consequence of the evolved biological function of HET-s in heterokaryon incompatibility. Analysis of cross peak intensities in two-dimensional NMR spectra of uniformly labeled Ure2p(1-89) fibrils suggests that certain portions of the amino acid sequence may not participate in a rigid P-sheet structure, possibly including portions of the Asn-rich segment between residues 44 and 76. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NIDDK, Proteom & Mass Spect Facil, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU Intramural NIH HHS NR 77 TC 91 Z9 94 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 13 PY 2007 VL 46 IS 45 BP 13149 EP 13162 DI 10.1021/bi700826b PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 228XT UT WOS:000250766600026 PM 17953455 ER PT J AU Cerutti, E Campagnoli, MF Ferretti, M Garelli, E Crescenzio, N Rosolen, A Chiocchetti, A Lenardo, MJ Ramenghi, U Dianzani, U AF Cerutti, Elisa Campagnoli, Maria F. Ferretti, Massimo Garelli, Emanuela Crescenzio, Nicoletta Rosolen, Angelo Chiocchetti, Annalisa Lenardo, Michael J. Ramenghi, Ugo Dianzani, Umberto TI Co-inherited mutations of Fas and caspase-10 in development of the autoimmune lymphoproliferative syndrome SO BMC IMMUNOLOGY LA English DT Article ID GENE-MUTATIONS; DEFECTIVE LYMPHOCYTE; APOPTOSIS PATHWAY; PERFORIN GENE; AUTOIMMUNITY/LYMPHOPROLIFERATION; DISORDER; DEFICIENCY; ACTIVATION; EXPRESSION; DISEASE AB Background: Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder characterized by defective function of Fas, autoimmune manifestations that predominantly involve blood cells, polyclonal accumulation of lymphocytes in the spleen and lymph nodes with lymphoadenomegaly and/or splenomegaly, and expansion of TCR alpha beta+ CD4/CD8 double-negative (DN) T cells in the peripheral blood. Most frequently, it is due to Fas gene mutations, causing ALPS type Ia (ALPS-Ia). However, other mutations, namely of the FasL gene (ALPS-Ib) and the caspase-10 gene (ALPS-II) are occasionally detected, whereas some patients do not present any known mutations (ALPS-III). Recently, mutations of the NRAS gene have been suggested to cause ALPS-IV. Results: This work reports two patients that are combined heterozygous for single nucleotide substitutions in the Fas and caspase-10 genes. The first patient carried a splice site defect suppressing allele expression in the Fas gene and the P501L substitution in caspase-10. The second had a mutation causing a premature stop codon (Q47X) in the Fas gene and the Y446C substitution in caspase-10. Fas expression was reduced and caspase-10 activity was decreased in both patients. In both patients, the mutations were inherited from distinct healthy parents. Conclusion: These data strongly suggest that co-transmission of these mutation was responsible for ALPS. C1 [Cerutti, Elisa; Ferretti, Massimo; Chiocchetti, Annalisa; Dianzani, Umberto] A Avogadro Univ Eastern Piedmont, IRCAD, Novara, Italy. [Cerutti, Elisa; Ferretti, Massimo; Chiocchetti, Annalisa; Dianzani, Umberto] A Avogadro Univ Eastern Piedmont, Dept Med Sci, Novara, Italy. [Campagnoli, Maria F.; Garelli, Emanuela; Crescenzio, Nicoletta; Ramenghi, Ugo] Univ Turin, Dept Pediat, I-10124 Turin, Italy. [Rosolen, Angelo] Univ Padua, Dept Pediat, Padua, Italy. [Lenardo, Michael J.] NIAID, NIH, Mol Dev Sect, Bethesda, MD 20892 USA. RP Dianzani, U (reprint author), A Avogadro Univ Eastern Piedmont, IRCAD, Novara, Italy. EM cerutti@med.unipmn.it; campagnolifra@yahoo.com; ferretti@med.unipmn.it; emanuela.garelli@unito.it; nicoletta.crescenzio@unito.it; rosolen@pediatria.unipd.it; chiocche@med.unipmn.it; MLENARDO@niaid.nih.gov; ramenghi@pediatria.unito.it; dianzani@med.unipmn.it RI Dianzani, Umberto/K-1952-2016 FU Telethon [GGP04071] NR 31 TC 13 Z9 15 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD NOV 13 PY 2007 VL 8 AR 28 DI 10.1186/1471-2172-8-28 PG 9 WC Immunology SC Immunology GA 257DA UT WOS:000252778200001 PM 17999750 ER PT J AU Elshal, MF Khan, SS Raghavachari, N Takahashi, Y Barb, J Bailey, JJ Munson, PJ Solomon, MA Danner, RL Mccoy, JP AF Elshal, Mohamed F. Khan, Sameena S. Raghavachari, Nalini Takahashi, Yoshiyuki Barb, Jennifer Bailey, James J. Munson, Peter J. Solomon, Michael A. Danner, Robert L. McCoy, J. Philip, Jr. TI A unique population of effector memory lymphocytes identified by CD146 having a distinct immunophenotypic and genomic profile SO BMC IMMUNOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; PERIPHERAL-BLOOD; T-LYMPHOCYTES; ADHESION; ACTIVATION; ANTIGEN; EXPRESSION AB Background: CD146 is a well described homotypic adhesion molecule found on endothelial cells and a limited number of other cell types. In cells from the peripheral circulation, CD146 has also been reported to be on activated lymphocytes in vitro and in vivo. The function associated with CD146 expression on lymphoid cells is unknown and very little information is available concerning the nature of CD146+ lymphocytes. In the current study, lymphocytes from healthy donors were characterized based upon the presence or absence of CD146 expression. Results: CD146 was expressed on a low percentage of circulating T lymphocytes, B lymphocytes, and NK cells in healthy individuals. CD146 expression can be induced and upregulated in vitro on both B cells and T cells, but does not correlate with the expression of other markers of T cell activation. CD146 positive T cells do not represent clonal expansions as determined with the use of anti V beta reagents. Data suggest that CD146 positive cells have enhanced adherence to endothelial monolayers in vitro. Gene profiling and immunophenotyping studies between CD146+ and CD146-T cells revealed several striking genotypic distinctions such as the upregulation of IL-8 and phenotypic differences including the paucity of CCR7 and CD45RA among CD146 positive T cells, consistent with effector memory function. A number of genes involved in cell adhesion, signal transduction, and cell communication are dramatically upregulated in CD146+ T cells compared to CD146-T cells. Conclusion: CD146 appears to identify small, unique populations of T as well as B lymphocytes in the circulation. The T cells have immunophenotypic characteristics of effector memory lymphocytes. The characteristics of these CD146+ lymphocytes in the circulation, together with the known functions in cell adhesion of CD146 on endothelial cells, suggests that these lymphocytes may represent a small subpopulation of cells primed to adhere to the endothelium and possibly extravasate to sites of inflammation. C1 [Elshal, Mohamed F.; McCoy, J. Philip, Jr.] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. [Khan, Sameena S.; Raghavachari, Nalini; Solomon, Michael A.; Danner, Robert L.] NIH, Funct Genom Proteom Facil, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Takahashi, Yoshiyuki; McCoy, J. Philip, Jr.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Solomon, Michael A.] NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. [Elshal, Mohamed F.] Minoufiya Univ, Dept Mol Biol, Genet Engn & Biotechnol Inst, Minoufiya, Egypt. RP Mccoy, JP (reprint author), NHLBI, Flow Cytometry Core Facil, NIH, Bldg 10, Bethesda, MD 20892 USA. EM melshal2002@yahoo.com; sarwaree@earthlink.net; nraghavachari@mail.nih.gov; ytakaha@med.nagoya-u.ac.jp; barbj@mail.nih.gov; baileyj@mail.nih.gov; munson@mail.nih.gov; msolomon@mail.nih.gov; dannerr@mail.nih.gov; mccoyjp@mail.nih.gov RI Elshal, Mohamed/H-7953-2012; Takahashi, Yoshiyuki/I-1929-2012 FU Intramural NIH HHS NR 19 TC 31 Z9 31 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD NOV 13 PY 2007 VL 8 AR 29 DI 10.1186/1471-2172-8-29 PG 15 WC Immunology SC Immunology GA 274AC UT WOS:000253972700001 PM 17999761 ER PT J AU Laurin, D Masaki, KH White, LR Launer, LJ AF Laurin, Danielle Masaki, Kamal H. White, Lon R. Launer, Lenore J. TI Ankle-to-brachial index and dementia - The Honolulu-Asia aging study SO CIRCULATION LA English DT Article DE aging; apolipoproteins; epidemiology; peripheral vascular disease; population; risk factors ID PERIPHERAL ARTERIAL-DISEASE; CORONARY-HEART-DISEASE; VASCULAR-DISEASE; COGNITIVE FUNCTION; ALZHEIMERS-DISEASE; CARDIOVASCULAR-DISEASE; APOLIPOPROTEIN-E; BLOOD-PRESSURE; RISK-FACTORS; ELDERLY-MEN AB Background-Measurement of the ankle-to-brachial index (ABI) is a noninvasive test to assess peripheral arterial disease. A low ABI is a strong correlate of cardiovascular disease and subsequent mortality. Evidence indicates the existence of vascular components in the pathogenesis of dementia. Here, we examine the association of ABI with dementia and subtypes. Methods and Results-Data are from the Honolulu-Asia Aging Study (HAAS), a prospective community-based study of 3734 Japanese American men 71 to 93 years of age at baseline in 1991 to 1993. The analysis included 2588 men who were free of dementia at the first assessment, had an ABI measure, and were examined up to 2 more times for dementia between 1994 and 1999. The sample included 240 incident cases of dementia (144 of Alzheimer's disease, 46 of vascular dementia, and 50 of dementia of other causes). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from Cox proportional-hazards models with age as the time scale after adjustment for education, year of birth, high blood pressure, body mass index, diabetes mellitus, cholesterol concentration, smoking status, alcohol consumption, and apolipoprotein E epsilon 4 allele. A low ABI was associated with an increased risk of dementia and vascular dementia (HR, 1.66; 95% CI, 1.16 to 2.37; and HR, 2.25; 95% CI, 1.07 to 4.73, respectively). ABI was weakly associated with Alzheimer's disease (HR, 1.57; 95% CI, 0.98 to 2.53), particularly in the apolipoprotein E epsilon 4 carriers (HR, 1.43; 95% CI, 1.02 to 1.96). Conclusions-These results suggest that ABI, a measure of atherosclerosis, is associated with the incidence of total dementia, vascular dementia, and Alzheimer's disease in carriers of the apolipoprotein E epsilon 4 allele. C1 NIH, NIA, Lab Epidemiol Demography & Biometry, Bethesda, MD 20892 USA. Univ Laval, Fac Pharm, Ctr Rech, CHA,Laval Univ Geriatr Res Unit, Quebec City, PQ, Canada. Kuakini Med Ctr, Pacific Hlth Res Inst, Honolulu, HI USA. NIH, NIA, Lab Epidemiol Demography & Biometry, Neuroepidemiol Sect, Bethesda, MD USA. RP Launer, LJ (reprint author), NIH, NIA, Lab Epidemiol Demography & Biometry, Gateway Bldg,Rm 3C309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [N01 HC05102]; NIA NIH HHS [R01 AG0-17155 S1, U01 AG019349] NR 41 TC 36 Z9 37 U1 2 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 NOV 13 PY 2007 VL 116 IS 20 BP 2269 EP 2274 DI 10.1161/CIRCULATIONAHA.106.686477 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 230IT UT WOS:000250870900006 PM 17967779 ER PT J AU Lehnart, SE Ackerman, MJ Benson, W Grant, AO Groft, SC January, CT Lathrop, DA Lederer, WJ Makielski, JC Mohler, PJ Moss, A Nerbonne, JM Olson, TM Przywara, DA Towbin, JA Wang, LH Marks, AR AF Lehnart, Stephan E. Ackerman, Michael J. Benson, Woodrow, Jr. Grant, Augustus O. Groft, Stephen C. January, Craig T. Lathrop, David A. Lederer, W. Jonathan Makielski, Jonathan C. Mohler, Peter J. Moss, Arthur Nerbonne, Jeanne M. Olson, Timothy M. Przywara, Dennis A. Towbin, Jeffrey A. Wang, Lan-Hsiang Marks, Andrew R. TI Inherited Arrhythmias - A national heart, lung, and blood institute and office of rare diseases workshop consensus report about the diagnosis, phenotyping, molecular mechanisms, and therapeutic approaches for primary cardiomyopathies of gene mutations affecting ion channel function SO CIRCULATION LA English DT Review DE arrhythmia; cardiomyopathies; death, sudden; electrophysiology; genetics; ion channels; long-QT syndrome ID LONG-QT SYNDROME; POLYMORPHIC VENTRICULAR-TACHYCARDIA; SUDDEN CARDIAC DEATH; OF-FUNCTION MUTATION; FAMILIAL ATRIAL-FIBRILLATION; ACTION-POTENTIAL DURATION; RYANODINE RECEPTOR GENE; SICK SINUS SYNDROME; LATE SODIUM CURRENT; BRUGADA-SYNDROME AB The National Heart, Lung, and Blood Institute and Office of Rare Diseases at the National Institutes of Health organized a workshop ( September 14 to 15, 2006, in Bethesda, Md) to advise on new research directions needed for improved identification and treatment of rare inherited arrhythmias. These included the following: (1) Na+ channelopathies; (2) arrhythmias due to K+ channel mutations; and (3) arrhythmias due to other inherited arrhythmogenic mechanisms. Another major goal was to provide recommendations to support, enable, or facilitate research to improve future diagnosis and management of inherited arrhythmias. Classifications of electric heart diseases have proved to be exceedingly complex and in many respects contradictory. A new contemporary and rigorous classification of arrhythmogenic cardiomyopathies is proposed. This consensus report provides an important framework and overview to this increasingly heterogeneous group of primary cardiac membrane channel diseases. Of particular note, the present classification scheme recognizes the rapid evolution of molecular biology and novel therapeutic approaches in cardiology, as well as the introduction of many recently described diseases, and is unique in that it incorporates ion channelopathies as a primary cardiomyopathy in consensus with a recent American Heart Association Scientific Statement. C1 Columbia Univ, Coll Phys & Surg, Clyde & Helen Wu Ctr Mol Cardiol, Dept Physiol & Cellular Biophys,Dept Med, New York, NY 10032 USA. Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. Mayo Clin, Div Pediat Cardiol, Rochester, MN USA. Childrens Hosp, Med Ctr, Div Cardiol & Mol Cardiovasc Biol, Cincinnati, OH 45229 USA. Univ Montreal, Clin Cardiovasc Genet Ctr, Montreal Heart Inst, Montreal, PQ, Canada. Cornell Univ, Weill Med Coll, Inst Computat Biomed, New York, NY USA. Case Western Reserve Univ, MetroHlth Hosp, Heart & Vasc Res Ctr, Cleveland, OH 44106 USA. Vanderbilt Univ, Div Med Genet, Nashville, TN USA. Duke Univ, Durham, NC USA. NIH, Bethesda, MD 20892 USA. Univ Wisconsin Hosp & Clin, Cardiol Sect, Madison, WI 53792 USA. NHLBI, NIH, Div Cardiovasc Dis, Bethesda, MD 20892 USA. Univ Maryland, Ctr Med Biotechnol, Inst Biotechnol, Baltimore, MD 21201 USA. Univ Wisconsin, Cardiovasc Med Sect, Madison, WI USA. Univ Iowa, Carver Coll Med, Div Cardiol, Iowa City, IA USA. Univ Rochester, Med Ctr, Div Cardiol, Rochester, NY 14642 USA. Washington Univ, Sch Med, Ctr Cardiovasc Res & Mol Biol, St Louis, MO USA. Mayo Clin, Div Cardiovasc Dis, Cardiovasc Genet Lab, Rochester, MN USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. RP Lehnart, SE (reprint author), Columbia Univ, Coll Phys & Surg, Clyde & Helen Wu Ctr Mol Cardiol, Dept Physiol & Cellular Biophys,Dept Med, New York, NY 10032 USA. EM sel2004@columbia.edu RI LATHROP, David/A-2758-2008; Lederer, William/B-1285-2010 FU NHLBI NIH HHS [R01 HL085592] NR 183 TC 151 Z9 163 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 13 PY 2007 VL 116 IS 20 BP 2325 EP 2345 DI 10.1161/CIRCULATIONAHA.107.711689 PG 21 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 230IT UT WOS:000250870900013 PM 17998470 ER PT J AU Bushel, PR Heinloth, AN Li, J Huang, L Chou, JW Boorman, GA Malarkey, DE Houle, CD Ward, SM Wilson, RE Fannin, RD Russo, MW Watkins, PB Tennant, RW Paules, RS AF Bushel, P. R. Heinloth, A. N. Li, J. Huang, L. Chou, J. W. Boorman, G. A. Malarkey, D. E. Houle, C. D. Ward, S. M. Wilson, R. E. Fannin, R. D. Russo, M. W. Watkins, P. B. Tennant, R. W. Paules, R. S. TI Blood gene expression signatures predict exposure levels SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE acetaminophen; hepatotoxicity; microarray; prediction; genomics ID ACUTE LIVER-FAILURE; COMPLICATIONS; INFLAMMATION; PROFILES; TOXICITY; BIOPSY AB To respond to potential adverse exposures properly, health care providers need accurate indicators of exposure levels. The indicators are particularly important in the case of acetaminophen (APAP) intoxication, the leading cause of liver failure in the U.S. We hypothesized that gene expression patterns derived from blood cells would provide useful indicators of acute exposure levels. To test this hypothesis, we used a blood gene expression data set from rats exposed to APAP to train classifiers in two prediction algorithms and to extract patterns for prediction using a profiling algorithm. Prediction accuracy was tested on a blinded, independent rat blood test data set and ranged from 88.9% to 95.8%. Genomic markers outperformed predictions based on traditional clinical parameters. The expression profiles of the predictor genes from the patterns extracted from the blood exhibited remarkable (97% accuracy) transtissue APAP exposure prediction when liver gene expression data were used as a test set. Analysis of human samples revealed separation of APAP-intoxicated patients from control individuals based on blood expression levels of human orthologs of the rat discriminatory genes. The major biological signal in the discriminating genes was activation of an inflammatory response after exposure to toxic doses of APAP. These results support the hypothesis that gene expression data from peripheral blood cells can provide valuable information about exposure levels, well before liver damage is detected by classical parameters. It also supports the potential use of genomic markers in the blood as surrogates for clinical markers of potential acute liver damage. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Stress & Canc Grp, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA. NIEHS, Canc Biol Grp, Res Triangle Pk, NC 27709 USA. Expt Pathol Labs Inc, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. RP Paules, RS (reprint author), 111 Alexander Dr,Mail Drop D2-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM paules@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [N01ES25497, N01ES95442, N01ES35513] NR 23 TC 78 Z9 87 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 NOV 13 PY 2007 VL 104 IS 46 BP 18211 EP 18216 DI 10.1073/pnas.0706987104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233FY UT WOS:000251077000057 PM 17984051 ER PT J AU Lu, H Zuo, Y Gu, H Waltz, JA Zhan, W Scholl, CA Rea, W Yang, Y Stein, EA AF Lu, Hanbing Zuo, Yantao Gu, Hong Waltz, James A. Zhan, Wang Scholl, Clara A. Rea, William Yang, Yihong Stein, Elliot A. TI Synchronized delta oscillations correlate with the resting-state functional MRI signal SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE electroencephalogram; spontaneous fluctuations; functional connectivity ID VISUAL-CORTEX; FOREPAW STIMULATION; GAMMA-OSCILLATIONS; ALZHEIMER-DISEASE; NUCLEUS-ACCUMBENS; HUMAN BRAIN; CONNECTIVITY; RAT; NETWORKS; SLEEP AB Synchronized low-frequency spontaneous fluctuations of the functional MRI (fMRI) signal have recently been applied to investigate large-scale neuronal networks of the brain in the absence of specific task instructions. However, the underlying neural mechanisms of these fluctuations remain largely unknown. To this end, electrophysiological recordings and resting-state fMRI measurements were conducted in alpha-chloralose-anesthetized rats. Using a seed-voxel analysis strategy, region-specific, anesthetic dose-dependent fMRI resting-state functional connectivity was detected in bilateral primary somatosensory cortex (S1FL) of the resting brain. Cortical electroencephalographic signals were also recorded from bilateral S1FL; a visual cortex locus served as a control site. Results demonstrate that, unlike the evoked fMRI response that correlates with power changes in the gamma bands, the resting-state fMRI signal correlates with the power coherence in low-frequency bands, particularly the delta band. These data indicate that hemodynamic fMRI signal differentially registers specific electrical oscillatory frequency band activity, suggesting that fMRI may be able to distinguish the ongoing from the evoked activity of the brain. C1 NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. RP Yang, Y (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM yihongyang@intra.nida.nih.gov; estein@intra.nida.nih.gov RI Stein, Elliot/C-7349-2008 FU Intramural NIH HHS NR 50 TC 189 Z9 191 U1 1 U2 19 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 NOV 13 PY 2007 VL 104 IS 46 BP 18265 EP 18269 DI 10.1073/pnas.0705791104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233FY UT WOS:000251077000066 PM 17991778 ER PT J AU Maggio, M Lauretani, F Ceda, GP Bandinelli, S Ling, SM Metter, EJ Artoni, A Carassale, L Cazzato, A Ceresini, G Guralnik, JM Basaria, S Valenti, G Ferrucci, L AF Maggio, Marcello Lauretani, Fulvio Ceda, Gian Paolo Bandinelli, Stefania Ling, Shari M. Metter, E. Jeffrey Artoni, Andrea Carassale, Laura Cazzato, Anna Ceresini, Graziano Guralnik, Jack M. Basaria, Shehzad Valenti, Giorgio Ferrucci, Luigi TI Relationship between low levels of anabolic hormones and 6-year mortality in older men - The aging in the Chianti area (InCHIANTI) study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID GROWTH-FACTOR-I; CHRONIC HEART-FAILURE; DEHYDROEPIANDROSTERONE-SULFATE; CARDIOVASCULAR-DISEASE; ELDERLY-MEN; IGF-I; TESTOSTERONE; WOMEN; SERUM; MUSCLE AB Background: Aging in men is characterized by a progressive decline in levels of anabolic hormones, such as testosterone, insulinlike growth factor 1 (IGF-1), and dehydroepiandrosterone sulfate (DHEA-S). We hypothesized that in older men a parallel age-associated decline in bioavailable testosterone, IGF-1, and DHEA-S secretion is associated with higher mortality independent of potential confounders. Methods: Testosterone, IGF-1, DHEA-S, and demographic features were evaluated in a representative sample of 410 men 65 years and older enrolled in the Aging in the Chianti Area (InCHIANTI) study. A total of 126 men died during the 6-year follow-up. Thresholds for lowest-quartile definitions were 70 ng/dL (to convert to nanomoles per liter, multiply by 0.0347) for bioavailable testosterone, 63.9 ng/mL (to convert to nanomoles per liter, multiply by 0.131) for total IGF-1, and 50 pg/dL (to convert to micromoles per liter, multiply by 0.027) for DHEA-S. Men were divided into 4 groups: no hormone in the lowest quartile (reference) and 1, 2, and 3 hot-mones in the lowest quartiles. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis. Results: Compared with men with levels of all 3 hormones above the lowest quartiles, having 1, 2, and 3 dys-regulated hormones was associated with hazard ratios for mortality of 1.47 (95% confidence interval [CI], 0.882.44), 1.85 (95% CI, 1.04-3.30), and 2.29 (95% CI, 1.124.68), respectively (test for trend, P < .001). In the fully adjusted analysis, only men with 3 anabolic hormone deficiencies had a significant increase in mortality (hazard ratio, 2.44; 95% CI, 1.09-5.46 (test for trend, P < .001). Conclusions: Age-associated decline in anabolic hormone levels is a strong independent predictor of mortality in older men. Having multiple hormonal deficiencies rather than a deficiency in a single anabolic hormone is a robust biomarker of health status in older persons. C1 NIA, NIH, Longitudinal Studies Sect, Clin Res Branch,Intramural Res Program, Baltimore, MD 21225 USA. Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, I-43100 Parma, Italy. Tuscany Reg Hlth Agcy, Florence, Italy. ASF Florence, Geriatr Rehabil Unit, Florence, Italy. Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Dept Med,Div Endocrinol, Baltimore, MD USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), NIA, NIH, Longitudinal Studies Sect, Clin Res Branch,Intramural Res Program, 3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01 AG 916413, N01 AG 821336]; NIMHD NIH HHS [R01 MD009164] NR 36 TC 127 Z9 129 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 12 PY 2007 VL 167 IS 20 BP 2249 EP 2254 DI 10.1001/archinte.167.20.2249 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 229LT UT WOS:000250806200013 PM 17998499 ER PT J AU Sajaev, V Borland, M Chae, YC Decker, G Dejus, R Emery, L Harkay, K Nassiri, A Shastri, S Waldschmidt, G Yang, B Anfinrud, P Dolgashev, V AF Sajaev, V. Borland, M. Chae, Y. -C. Decker, G. Dejus, R. Emery, L. Harkay, K. Nassiri, A. Shastri, S. Waldschmidt, G. Yang, B. Anfinrud, P. Dolgashev, V. TI Short X-ray pulse generation using deflecting cavities at the Advanced Photon Source SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article; Proceedings Paper CT 14th National Conference on Synchrotron Radiation Instrumentation CY APR 25-27, 2007 CL Baton Rouge, LA SP Louisiana State Univ DE synchrotron radiation sources AB Storage-ring-based third-generation light sources can provide intense radiation pulses with durations as short as 100 ps. However, there is growing interest within the synchrotron radiation user community in performing experiments with much shorter X-ray pulses. Zholents et al. [Nucl. Instr. and Meth. A 425 (1999) 385] recently proposed using RF orbit deflection to generate sub-ps X-ray pulses. In this scheme, two deflecting cavities are used to deliver a longitudinally dependent vertical kick to the beam. An optical slit can then be used to slice out a short part of the radiation pulse. Implementation of this scheme is planned for one APS beamline in the near future. In this paper, we summarize our feasibility study of this method and the expected X-ray beam parameters. We find that a pulse length of less than two picoseconds can be achieved. Published by Elsevier B.V. C1 Argonne Natl Lab, Argonne, IL 60439 USA. NIH, NIDDK, Bethesda, MD 20892 USA. SLAC, Menlo Pk, CA 94025 USA. RP Sajaev, V (reprint author), Argonne Natl Lab, 9700 S Cass Ave, Argonne, IL 60439 USA. EM sajaev@aps.anl.gov NR 6 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD NOV 11 PY 2007 VL 582 IS 1 BP 57 EP 59 DI 10.1016/j.nima.2007.08.060 PG 3 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 232SK UT WOS:000251039500017 ER PT J AU Green, JA Yamada, KM AF Green, J. Angelo Yamada, Kenneth M. TI Three-dimensional microenvironments modulate fibroblast signaling responses SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE fibroblast; fibronectin; three-dimensional matrix; integrin signaling; Rho GTPases ID CELL-BINDING DOMAIN; SITE-DIRECTED MUTAGENESIS; ADHESIVE FUNCTION; 3D MATRIX; FIBRONECTIN; MIGRATION; ALPHA(5)BETA(1); DIFFERENTIATION; INHIBITION; RECEPTORS AB Modes of signaling in fibroblasts can differ substantially depending on whether these cells are in their natural three-dimensional environment compared to artificial two-dimensional culture conditions. Although studying cell behavior in two-dimensional environments has been valuable for understanding biological processes, questions can be raised about their in vivo physiological relevance. This review focuses on some of our research involving fibroblast behavior in cell-derived three-dimensional matrices. Specifically, we examine how these matrices affect cell morphology, adhesion, proliferation, and signaling compared to two-dimensional substrates. We stress the importance of controls for three-dimensional matrix studies and discuss cancer as an example in which altered three-dimensional matrices can influence fibroblast signaling. Studying cells in three-dimensional microenvironments can lead to the design of more physiologically relevant conditions for assaying drug responses and deciphering biological mechanisms. Published by Elsevier B.V. C1 [Green, J. Angelo; Yamada, Kenneth M.] Natl Inst Hlth, Natl Inst Dental & Craniofacial Res, Lab Cell & Dev Biol, Bethesda, MD 20892 USA. RP Yamada, KM (reprint author), Natl Inst Hlth, Natl Inst Dental & Craniofacial Res, Lab Cell & Dev Biol, 30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM kenneth.yamada@nih.gov OI Yamada, Kenneth/0000-0003-1512-6805 FU Intramural NIH HHS [Z01 DE000525-17, Z01 DE000524-17] NR 28 TC 60 Z9 62 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD NOV 10 PY 2007 VL 59 IS 13 BP 1293 EP 1298 DI 10.1016/j.addr.2007.08.005 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 242YP UT WOS:000251762400002 PM 17825946 ER PT J AU Clauser, SB Ganz, PA Lipscomb, J Reeve, BB AF Clauser, Steven B. Ganz, Patricia A. Lipscomb, Joseph Reeve, Bryce B. TI Patient-reported outcomes assessment in cancer trials: Evaluating and enhancing the payoff to decision making SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. Emory Univ, Atlanta, GA 30322 USA. RP Clauser, SB (reprint author), NCI, Bethesda, MD 20892 USA. NR 7 TC 27 Z9 27 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2007 VL 25 IS 32 BP 5049 EP 5050 DI 10.1200/JCO.2007.14.5888 PG 2 WC Oncology SC Oncology GA 233EW UT WOS:000251074200001 PM 17991919 ER PT J AU Brundage, M Osoba, D Bezjak, A Tu, DS Palmer, M Pater, J AF Brundage, Michael Osoba, David Bezjak, Andrea Tu, Dongsheng Palmer, Michael Pater, Joseph TI Lessons learned in the assessment of health-related quality of life: Selected examples from the national cancer institute of Canada clinical trials group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID LUNG-CANCER; RANDOMIZED-TRIAL; BREAST-CANCER; EORTC QLQ-C30; CHEMOTHERAPY; INFORMATION; RELIABILITY; COMPLETION; TOXICITY; SCORES AB In this article, we provide a brief historical review of the development of patient-reported outcome measurement, analysis, and reporting in clinical trials of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG). In doing so, we examine selected lessons learned in furthering the quality of these data and their application to clinical practice. We conclude that sequential institution of key policies within the NCIC CTG and the development of a collective philosophy within the group has enabled the routine incorporation of health-related quality of life into clinical trial protocols according to robust scientific principles; that collection of quality data is possible in a variety of circumstances (although not universally so); that patient-reported data on subjective experiences is likely to be more reliable and valid than conventional toxicity information; and that simple analyses that report group trends as well as individual patient response rates are preferred. C1 Queens Univ, Queens Canc Res Inst, Clin Trials Grp, Dept Oncol, Kingston, ON, Canada. Queens Univ, Queens Canc Res Inst, Clin Trials Grp, Dept Community Hlth & Epidemiol, Kingston, ON, Canada. Queens Univ, Queens Canc Res Inst, Clin Trials Grp, NCI, Kingston, ON, Canada. Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. QOL Consulting, W Vancouver, BC, Canada. RP Brundage, M (reprint author), SE Ontario Kingston Gen Hosp, Canc Clin, 25 King St W, Kingston, ON K7L 5P9, Canada. EM michael.brundage@krcc.on.ca NR 26 TC 19 Z9 20 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2007 VL 25 IS 32 BP 5078 EP 5081 DI 10.1200/JCO.2007.11.4645 PG 4 WC Oncology SC Oncology GA 233EW UT WOS:000251074200006 PM 17991924 ER PT J AU Moinpour, CM Denicoff, AM Bruner, DW Kornblith, AB Land, SR O'Mara, A Trimble, E AF Moinpour, Carol M. Denicoff, Andrea M. Bruner, Deborah Watkins Kornblith, Alice B. Land, Stephanie R. O'Mara, Ann Trimble, Edward TI Funding patient-reported outcomes in cancer clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID FUNCTIONAL LIVING INDEX; QUALITY; LIFE AB We surveyed four cooperative groups to identify current funding sources for the collection and analysis effort associated with the inclusion of patient-reported outcome (PRO) data in cancer clinical trials. Survey questions included what proportion of staff effort was funded through the Cancer Therapy Evaluation Program (CTEP) and the Community Clinical Oncology Program (CCOP) grants. In addition, the groups were asked to what extent outside funding was solicited to cover an underfunded PRO effort (eg, the pharmaceutical industry, foundations, or National Institutes of Health grants). All four groups noted the challenge of making limited resources cover a number of trial responsibilities. PRO effort is usually bundled with effort required for all clinical trial data. There is variation in the use of the CTEP and CCOP grants to fund PRO research. The groups differed with respect to both the types and amount of outside funding used. This survey focused on funding sources for the conduct of PRO research in cooperative group trials; it did not assess the specific cost components associated with collecting and analyzing these data. In general, the costs for conducting PRO research have been bundled with other study costs because in most cases, the PRO has been considered an integral component of the trial. However, these data also suggest that PRO research has required the use of outside funding sources in the four surveyed cooperative groups and that PRO economic issues require attention if we are to continue the inclusion of these outcomes in cancer clinical trials. C1 Fred Hutchinson Canc Res Ctr, Ctr Stat, SW Oncol Grp, Seattle, WA 98104 USA. NCI, Clin Invest Branch, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. NCI, Community Clin Oncol Program, NIH, Bethesda, MD 20892 USA. Univ Penn, Radiat Therapy Oncol Grp, Philadelphia, PA 19104 USA. Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Program, Ctr Biostat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. Dana Farber Canc Ctr, Canc & Leukemia Grp B, Boston, MA USA. RP Moinpour, CM (reprint author), Fred Hutchinson Canc Res Ctr, Ctr Stat, SW Oncol Grp, MS-C102,1100 Fairview Ave N,Box 19024, Seattle, WA 98104 USA. EM cmoinpou@fhcrc.org FU NCI NIH HHS [CA31946, CA38926, CA069974, CA37422, CA37429, CA21661, CA32115] NR 31 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2007 VL 25 IS 32 BP 5100 EP 5105 DI 10.1200/JCO.2007.11.5329 PG 6 WC Oncology SC Oncology GA 233EW UT WOS:000251074200010 PM 17991928 ER PT J AU Garcia, SF Cella, D Clauser, SB Flynn, KE Lad, T Lai, JS Reeve, BB Smith, AW Stone, AA Weinfurt, K AF Garcia, Sofia F. Cella, David Clauser, Steven B. Flynn, Kathryn E. Lad, Thomas Lai, Jin-Shei Reeve, Bryce B. Smith, Ashley Wilder Stone, Arthur A. Weinfurt, Kevin TI Standardizing patient-reported outcomes assessment in cancer clinical trials: A patient-reported outcomes measurement information system initiative SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; PROMIS; COMMUNICATION; DEPRESSION AB Patient-reported outcomes (PROs), such as symptom scales or more broad-based health-related quality-of-life measures, play an important role in oncology clinical trials. They frequently are used to help evaluate cancer treatments, as well as for supportive and palliative oncology care. To be most beneficial, these PROs must be relevant to patients and clinicians, valid, and easily understood and interpreted. The Patient-Reported Outcomes Measurement Information System (PROMIS) Network, part of the National Institutes of Health Roadmap Initiative, aims to improve appreciably how PROs are selected and assessed in clinical research, including clinical trials. PROMIS is establishing a publicly available resource of standardized, accurate, and efficient PRO measures of major self-reported health domains (eg, pain, fatigue, emotional distress, physical function, social function) that are relevant across chronic illnesses including cancer. PROMIS is also developing measures of self-reported health domains specifically targeted to cancer, such as sleep/wake function, sexual function, cognitive function, and the psychosocial impacts of the illness experience (ie, stress response and coping; shifts in self-concept, social interactions, and spirituality). We outline the qualitative and quantitative methods by which PROMIS measures are being developed and adapted for use in clinical oncology research. At the core of this activity is the formation and application of item banks using item response theory modeling. We also present our work in the fatigue domain, including a short-form measure, as a sample of PROMIS methodology and work to date. Plans for future validation and application of PROMIS measures are discussed. C1 Evanston NW Healthcare, CORE, Evanston, IL 60201 USA. Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Dept Psychiat & Behav Sci, Evanston, IL 60208 USA. Northwestern Univ, Feinberg Sch Med, Dept Pediat, Evanston, IL 60208 USA. John H Stroger Jr Hosp Cook Cty, Div Hematol Oncol, Chicago, IL USA. NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Duke Clin Res Inst, Ctr Clin & Genet Econ, Durham, NC USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. RP Cella, D (reprint author), Evanston NW Healthcare, CORE, 1001 Univ Pl,Suite 100, Evanston, IL 60201 USA. EM d-cella@northwestern.edu RI Flynn, Kathryn/M-5346-2013 OI Flynn, Kathryn/0000-0002-4427-3583 FU NIAMS NIH HHS [U01AR052177, U01AR052186] NR 26 TC 138 Z9 138 U1 3 U2 16 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2007 VL 25 IS 32 BP 5106 EP 5112 DI 10.1200/JCO.2007.12.2341 PG 7 WC Oncology SC Oncology GA 233EW UT WOS:000251074200011 PM 17991929 ER PT J AU Land, SR Ritter, MW Costantino, JP Julian, TB Cronin, WM Haile, SR Wolmark, N Ganz, PA AF Land, Stephanie R. Ritter, Marcie W. Costantino, Joseph P. Julian, Thomas B. Cronin, Walter M. Haile, Sarah R. Wolmark, Norman Ganz, Patricia A. TI Compliance with patient-reported outcomes in multicenter clinical trials: Methodologic and practical approaches SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID QUALITY-OF-LIFE; ANTIPLATELET STROKE PREVENTION; BREAST-CANCER PREVENTION; STAR P-2 TRIAL; MISSING DATA; AFRICAN-AMERICANS; LUNG-CANCER; QUESTIONNAIRES; RECRUITMENT; EXPERIENCE AB Purpose This report describes interventions undertaken by the National Surgical Adjuvant Breast and Bowel Project (NSABP) to improve compliance with patient-reported outcome (PRO) assessments in the setting of multicenter cancer clinical trials. We describe the effectiveness of several interventions and of observational factors. Methods PRO submission rates were analyzed for the following three NSABP protocols: the Study of Raloxifene and Tamoxifen (STAR), B-32, and B-35. Institutions participating in protocol B-35 were randomly assigned to receive automated reminders of upcoming assessments or not. Compliance was analyzed with a logistic repeated measures mixed modeling. Results Compliance was high in the three protocols, with rates greater than 80% for nearly all time points. Institutions were a significant source of variability (P <.01). The largest institutions had the highest compliance in STAR (odds ratio [ OR] = 0.68 for < 50 participants enrolled and OR = 0.82 for 50 to 99 participants enrolled v larger institutions; P <.001). Midsized institutions had highest compliance in B-32 (OR = 4.63 for 31 to 50 patients enrolled and OR = 3.12 for > 50 patients enrolled v small institutions; P =.007). Compliance increased with participant age in STAR (OR = 0.57, 0.89, and 1.01 for ages < 50, 50 to 60, and 60 to 70 years, respectively, v > 70 years; P <.001). Race was significant in B-32 (OR = 2.63 for white v nonwhite; P <.001) and in STAR (OR = 1.41 for white v nonwhite; P <.001). Treatment group was significant in B-32 (OR = 0.74; P =.006). The B-35 prospective reminder did not improve compliance significantly (P =.30), but in B-32, delinquency sanctions were significant (OR = 1.56; P =.007). Conclusion Compliance in NSABP PRO studies is higher now than a decade ago. Results for compliance initiatives were mixed. Age and race are important factors, but institutional variation remains significant and largely unexplained. C1 Operat & Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth & Med, Los Angeles, CA 90024 USA. RP Land, SR (reprint author), Operat & Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project, 201 N Craig St,Ste 350, Pittsburgh, PA 15213 USA. EM land@pitt.edu RI Haile, Sarah/C-2330-2011 OI Haile, Sarah/0000-0002-4704-6570 FU NCI NIH HHS [U10-CA-12027, U10-CA-37377, U10-CA-69651, U10-CA-69974] NR 31 TC 12 Z9 12 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2007 VL 25 IS 32 BP 5113 EP 5120 DI 10.1200/JCO.2007.12.1749 PG 8 WC Oncology SC Oncology GA 233EW UT WOS:000251074200012 PM 17991930 ER PT J AU Trotti, A Colevas, AD Setser, A Basch, E AF Trotti, Andy Colevas, A. Dimitrios Setser, Ann Basch, Ethan TI Patient-reported outcomes and the evolution of adverse event reporting in oncology SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID QUALITY-OF-LIFE; CANCER-TREATMENT; CLINICAL-TRIALS; NECK-CANCER; END-POINTS; TOXICITY; HEAD; CHEMOTHERAPY; NEED; COMMUNICATION AB Adverse event (AE) reporting in oncology has evolved from informal descriptions to a highly systematized process. The Common Terminology Criteria for Adverse Events (CTCAE) is the predominant system for describing the severity of AEs commonly encountered in oncology clinical trials. CTCAE clinical descriptors have been developed empirically during more than 30 years of use. The method of data collection is clinician based. Limitations of the CTC system include potential for incomplete reporting and limited guidance on data analysis and presentation methods. The Medical Dictionary for Regulatory Activities (MedDRA) is a comprehensive medical terminology system used for regulatory reporting and drug labeling. MedDRA does not provide for severity ranking of AEs. CTC-based data presentations are the primary method of AE data reporting used in scientific journals and oncology meetings. Patient-reported outcome instruments (PROs) cover the subjective domain of AEs. Exploratory work suggests PROs can be used with a high degree of patient engagement and compliance. Additional studies are needed to determine how PROs can be used to complement current AE reporting systems. Potential models for integrating PROs into AE reporting are described in this review. AE reporting methods will continue to evolve in response to changing therapies and growing interest in measuring the impact of cancer treatment on health status. Although integration of PROs into AE reporting may ultimately improve the comprehensiveness and quality of collected data, it may also increase the administrative burden and cost of conducting trials. Therefore, care must be used when developing health outcomes and safety data collection plans. C1 Univ S Florida, H Lee Moffitt Canc Ctr, Div Radiat Oncol, Tampa, FL 33682 USA. Stanford Univ, Div Oncol, Stanford, CA 94305 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Hlth Outcomes Res Grp, New York, NY 10021 USA. RP Trotti, A (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr,Mod 9 RT, Tampa, FL 33612 USA. EM andy.trotti@moffitt.org FU NCI NIH HHS [K07 CA124851] NR 43 TC 108 Z9 108 U1 1 U2 13 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2007 VL 25 IS 32 BP 5121 EP 5127 DI 10.1200/JCO.2007.12.4784 PG 7 WC Oncology SC Oncology GA 233EW UT WOS:000251074200013 PM 17991931 ER PT J AU Minasian, LM O'Mara, AM Reeve, BB Denicoff, AM Kelaghan, J Rowland, JH Trimble, EL AF Minasian, Lori M. O'Mara, Ann M. Reeve, Bryce B. Denicoff, Andrea M. Kelaghan, Joseph Rowland, Julia H. Trimble, Edward L. TI Health-related quality of life and symptom management research sponsored by the National Cancer Institute SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID OVARIAN-CANCER; INTRAPERITONEAL AB For almost 30 years, the National Cancer Institute (NCI) has sponsored health-related quality-of-life (HRQOL) measures in cancer research as a means of including the patient's experience. The scope of NCI's research in symptom management and HRQOL is described with attention to its evolution over time and the next steps, through the Clinical Trials Working Group Recommendations. C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. NCI, Div Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Minasian, LM (reprint author), Community Oncol & Prevent Trials Res Grp, 6130 Execut Blvd,MSC 7340,EPN,Rm 2016, Bethesda, MD 20892 USA. EM minasilo@mail.nih.gov NR 14 TC 27 Z9 27 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2007 VL 25 IS 32 BP 5128 EP 5132 DI 10.1200/JCO.2007.12.6672 PG 5 WC Oncology SC Oncology GA 233EW UT WOS:000251074200014 PM 17991932 ER PT J AU Bonville, CA Bennett, NJ Percopo, CM Branigan, PJ Del Vecchio, AM Rosenberg, HF Domachowske, JB AF Bonville, Cynthia A. Bennett, Nicholas J. Percopo, Caroline M. Branigan, Patrick J. Del Vecchio, Alfred M. Rosenberg, Helene F. Domachowske, Joseph B. TI Diminished inflammatory responses to natural pneumovirus infection among older mice SO VIROLOGY LA English DT Article DE inflammation; granulocyte; respiratory; interleukin; chemokine; interferon ID RESPIRATORY SYNCYTIAL VIRUS; PNEUMONIA VIRUS; ELDERLY ADULTS; CYTOKINE; MODEL; IMMUNOPATHOLOGY; BRONCHIOLITIS; MACROPHAGES; DYSFUNCTION; MODULATION AB Immune responses to virus infection undergo significant change as part of the aging process. Here we examine the inflammatory responses of older. but otherwise immunologically naive mice to infection with pneumonia virus of mice (PVM). Although we see no changes in the extent or kinetics of virus replication, we observe diminished local production of inflammatory mediators, including MIP-1 alpha, JE/MCP-1, IFN-gamma and IFN-gamma-induced MIG and IP-10; and interleukins (IL)-6 and IL-17. Levels of KC and IL-l alpha remained unchanged. Age-dependent diminished production of proinflammatory mediators was associated with diminished recruitment of granulocytes and reduced severity of clinical responses, including weight loss and respiratory dysfunction. The differences observed when comparing these results to those reported among elderly human subjects may be related to the specific extent of aging and its impact on biochemical and cellular inflammatory responses and/or the role of lifetime virus re-exposure on the clinical outcome from acute pneumovirus disease. (C) 2007 Elsevier Inc. All rights reserved. C1 SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA. NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. Centocor Inc, Dept Infect Dis Res, Radnor, PA USA. RP Domachowske, JB (reprint author), SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA. EM domachoj@upstate.edu NR 33 TC 10 Z9 11 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 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2007 VL 368 IS 1 BP 182 EP 190 DI 10.1016/j.virol.2007.06.020 PG 9 WC Virology SC Virology GA 227SW UT WOS:000250679100019 PM 17655904 ER PT J AU Ihara, H Tsutsuki, H Ida, T Kozaki, S Tsuyama, S Moss, J AF Ihara, Hideshi Tsutsuki, Hiroyasu Ida, Tomoaki Kozaki, Shunji Tsuyama, Shingo Moss, Joel TI Alternative polyadenylation sites of human endothelial nitric oxide synthase mRNA SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE 3 '-untranslated region; alternative polyadenylation sites; eNOS ID 3 UNTRANSLATED REGION; ESCHERICHIA-COLI LIPOPOLYSACCHARIDE; INDUCED DOWN-REGULATION; NECROSIS-FACTOR-ALPHA; CELL-GROWTH; POSTTRANSCRIPTIONAL REGULATION; CYTOSOLIC PROTEINS; EXPRESSION; GENE; MECHANISMS AB The mRNA 3'-untranslated region (3'-UTR) has been shown to have important roles in the regulation of mRNA function. In this study, we investigated the human endothelial nitric oxide synthase (eNOS) 3'-UTR to evaluate its potential regulatory role. 3'-RACE analysis revealed that the human eNOS mRNA has multiple alternative polyadenylation sites. Apart from the proximal site (418 bp downstream of the stop codon), we identified two additional distal sites approximately 770 and 1478 bp downstream of the stop codon. In addition, Northern analysis showed that the usage of these sites differed among human tissues. Further, amounts of these eNOS mRNAs were changed during growth of cultured human aortic endothelial cells; mRNAs with long 3'-UTRs decreased more rapidly than total mRNA, as cells approached confluency. Thus, the 3'-UTRs of human eNOS results from alternative polyadenylation sites and differ across tissues and during cell growth. (C) 2007 Elsevier Inc. All rights reserved. C1 Osaka Prefecture Univ, Grad Sch Sci, Dept Biol Sci, Osaka 5998531, Japan. Osaka Prefecture Univ, Grad Sch Life & Environm Sci, Dept Vet Sci, Osaka 5998531, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Ihara, H (reprint author), Osaka Prefecture Univ, Grad Sch Sci, Dept Biol Sci, 1-1 Gakuen Cho, Osaka 5998531, Japan. EM ihara@b.s.osakafu-u.ac.jp FU Intramural NIH HHS [Z01 HL000659-15] NR 30 TC 4 Z9 4 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 9 PY 2007 VL 363 IS 1 BP 146 EP 152 DI 10.1016/j.bbrc.2007.08.118 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 219BR UT WOS:000250060200024 PM 17825792 ER PT J AU Bagley, J LaRocca, G Jimenez, DA Urban, NN AF Bagley, Joshua LaRocca, Greg Jimenez, Daniel A. Urban, Nathaniel N. TI Adult neurogenesis and specific replacement of interneuron subtypes in the mouse main olfactory bulb SO BMC NEUROSCIENCE LA English DT Article ID DEFINED NEURON GROUPS; GLOMERULAR LAYER; SUBVENTRICULAR ZONE; GRANULE CELLS; SUBPOPULATIONS; MIGRATION; BRAIN; PROLIFERATION; ORGANIZATION; POPULATION AB Background: New neurons are generated in the adult brain from stem cells found in the subventricular zone (SVZ). These cells proliferate in the SVZ, generating neuroblasts which then migrate to the main olfactory bulb (MOB), ending their migration in the glomerular layer (GLL) and the granule cell layer (GCL) of the MOB. Neuronal populations in these layers undergo turnover throughout life, but whether all neuronal subtypes found in these areas are replaced and when neurons begin to express subtype-specific markers is not known. Results: Here we use BrdU injections and immunohistochemistry against (calretinin, calbindin, N-copein, tyrosine hydroxylase and GABA) and show that adult-generated neurons express markers of all major subtypes of neurons in the GLL and GCL. Moreover, the fractions of new neurons that express subtype-specific markers at 40 and 75 days post BrdU injection are very similar to the fractions of all neurons expressing these markers. We also show that many neurons in the glomerular layer do not express NeuN, but are readily and specifically labeled by the fluorescent nissl stain Neurotrace. Conclusion: The expression of neuronal subtype-specific markers by new neurons in the GLL and GCL changes rapidly during the period from 14-40 days after BrdU injection before reaching adult levels. This period may represent a critical window for cell fate specification similar to that observed for neuronal survival. C1 [LaRocca, Greg; Urban, Nathaniel N.] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. [Bagley, Joshua; Urban, Nathaniel N.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA. [Urban, Nathaniel N.] Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA. [Urban, Nathaniel N.] NIH, NINDS, Bethesda, MD 20892 USA. RP Urban, NN (reprint author), Carnegie Mellon Univ, Dept Biol Sci, 4400 5th Ave, Pittsburgh, PA 15213 USA. EM bagleyjo@ninds.nih.gov; glarocca@andrew.cmu.edu; djimenez@gmail.com; nurban@cmu.edu RI Urban, Nathaniel/A-4974-2008 OI Urban, Nathaniel/0000-0002-0365-9068 FU NIDCD NIH HHS [R01DC005798] NR 32 TC 48 Z9 48 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD NOV 9 PY 2007 VL 8 AR 92 DI 10.1186/1471-2202-8-92 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 261VH UT WOS:000253107600001 PM 17996088 ER PT J AU Carlson, BA Moustafa, ME Sengupta, A Schweizer, U Shrimali, R Rao, M Zhong, N Wang, S Feigenbaum, L Lee, BJ Gladyshev, VN Hatfield, DL AF Carlson, Bradley A. Moustafa, Mohamed E. Sengupta, Aniruddha Schweizer, Ulrich Shrimali, Rajeev Rao, Mahadev Zhong, Nianxin Wang, Shulin Feigenbaum, Lionel Lee, Byeong Jae Gladyshev, Vadim N. Hatfield, Dolph L. TI Selective restoration of the selenoprotein population in a mouse hepatocyte selenoproteinless background with different mutant selenocysteine tRNAs lacking Um34 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYPE-2 IODOTHYRONINE DEIODINASE; GLUTATHIONE-PEROXIDASE; THIOREDOXIN REDUCTASE; ADAPTIVE THERMOGENESIS; TARGETED DISRUPTION; SELENIUM DEFICIENCY; MESSENGER-RNA; MICE LACKING; GENE TRSP; EXPRESSION AB Novel mouse models were developed in which the hepatic selenoprotein population was targeted for removal by disrupting the selenocysteine (Sec) tRNA([Ser]Sec) gene (trsp), and selenoprotein expression was then restored by introducing wild type or mutant trsp transgenes. The selenoprotein population was partially replaced in liver with mutant transgenes encoding mutations at either position 34(34T -> A) or 37 ( 37A -> G) in tRNA[ Ser] Sec. The A34 transgene product lacked the highly modified 5- methoxy-carbonylmethyl-2' -O-methyluridine, and its mutant base A was converted to I34. The G37 transgene product lacked the highly modified N-6-isopentenyladenosine. Both mutant tRNAs lacked the 2'-methylribose at position 34 ( Um34), and both supported expression of housekeeping selenoproteins ( e. g. thioredoxin reductase 1) in liver but not stress- related proteins ( e. g. glutathione peroxidase 1). Thus, Um34 is responsible for synthesis of a select group of selenoproteins rather than the entire selenoprotein population. The ICA anticodon in the A34 mutant tRNA decoded Cys codons, UGU and UGC, as well as the Sec codon, UGA. However, metabolic labeling of A34 transgenic mice with Se-75 revealed that selenoproteins incorporated the label from the A34 mutant tRNA, whereas other proteins did not. These results suggest that the A34 mutant tRNA did not randomly insert Sec in place of Cys, but specifically targeted selected selenoproteins. High copy numbers of A34 transgene, but not G37 transgene, were not tolerated in the absence of wild type trsp, further suggesting insertion of Sec in place of Cys in selenoproteins. C1 NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Canc Res Ctr,Natl Inst Hlth, Bethesda, MD 20892 USA. Charite Univ Med Berlin, Inst Expt Endocrinol, Ctr Res Neurosci, D-10117 Berlin, Germany. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. Seoul Natl Univ, Inst Mol Biol & Genet, Seoul 151742, South Korea. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Canc Res Ctr,Natl Inst Hlth, Bethesda, MD 20892 USA. EM hatfield@mail.nih.gov RI Gladyshev, Vadim/A-9894-2013; Schweizer, Ulrich/E-8105-2013; OI Schweizer, Ulrich/0000-0003-1380-4780 FU Intramural NIH HHS NR 52 TC 37 Z9 37 U1 0 U2 5 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 NOV 9 PY 2007 VL 282 IS 45 BP 32591 EP 32602 DI 10.1074/jbc.M707036200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226YW UT WOS:000250625400008 PM 17848557 ER PT J AU Ganguly, S Grodzki, C Sugden, D Moller, M Odom, S Gaildrat, P Gery, I Siraganian, RP Rivera, J Klein, DC AF Ganguly, Surajit Grodzki, Cristina Sugden, David Moller, Morten Odom, Sandra Gaildrat, Pascaline Gery, Igal Siraganian, Reuben P. Rivera, Juan Klein, David C. TI Neural adrenergic/cyclic AMP regulation of the immunoglobulin e receptor alpha-subunit expression in the mammalian pinealocyte a - Neuroendocrine/immune response link? SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FC-EPSILON-RI; ISOFORM MESSENGER-RNAS; AFFINITY IGE RECEPTOR; REAL-TIME PCR; N-ACETYLTRANSFERASE; CIRCADIAN EXPRESSION; GLAND; RAT; CELL; MELATONIN AB The high affinity immunoglobulin E receptor (Fc epsilon RI) complex is dedicated to immunoglobulin E- mediated allergic responses. Expression of the Fc epsilon RI receptor is thought to be relatively stable and limited to mast cells, basophils, eosinophils, monocytes, Langerhans cells, platelets, and neutrophils. We now report that the Fc epsilon RI alpha and Fc epsilon RI gamma polypeptides are expressed in the pinealocyte, the melatonin- secreting cell of the pineal gland. Moreover, Fcer1a mRNA levels increased similar to 100-fold at night to levels that were higher than in other tissues examined. Pineal Fc epsilon RI alpha protein also increased markedly at night from nearly undetectable daytime levels. Our studies indicate that pineal Fcer1a mRNA levels are controlled by a well described neural pathway that controls pineal function. This pathway includes the master circadian oscillator in the suprachiasmatic nucleus and passes through central and peripheral structures. The circadian expression of Fc epsilon RI alpha in the pineal gland is driven by this neural circuit via an adrenergic/ cyclic AMP mechanism. Pineal Fc epsilon RI alpha and Fc epsilon RI gamma may represent a previously unrealized molecular link between the neuroendocrine and immune systems. C1 NICHD, Sect Neuroendocrinol, Off Sci Director, Natl Inst Hlth, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. NIDCR, Oral Infect & Immun Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. Kings Coll London, Sch Biomed & Hlth Sci, Div Reprod & Endocrinol, London SE1 1UL, England. Univ Copenhagen, Panum Inst, Dept Neurobiol & Pharmacol, DK-2200 Copenhagen, Denmark. NIAMS, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. NEI, Immunol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Klein, DC (reprint author), NICHD, Sect Neuroendocrinol, Off Sci Director, Natl Inst Hlth, Bldg 49,Rm 6A82, Bethesda, MD 20892 USA. EM kleind@mail.nih.gov NR 45 TC 13 Z9 16 U1 0 U2 2 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 NOV 9 PY 2007 VL 282 IS 45 BP 32758 EP 32764 DI 10.1074/jbc.M705950200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226YW UT WOS:000250625400024 PM 17728245 ER PT J AU Modesti, M Budzowska, M Baldeyron, C Demmers, JAA Ghirlando, R Kanaar, R AF Modesti, Mauro Budzowska, Magda Baldeyron, Celine Demmers, Jeroen A. A. Ghirlando, Rodolfo Kanaar, Roland TI RAD51AP1 is a structure-specific DNA binding protein that stimulates joint molecule formation during RAD51-mediated homologous recombination SO MOLECULAR CELL LA English DT Article ID DOUBLE-STRAND BREAK; MEIOTIC RECOMBINATION; COMPLEX-FORMATION; RAD52 PROTEIN; NUCLEAR FOCI; IN-VITRO; REPAIR; REPLICATION; EXCHANGE; BRCA2 AB Homologous recombination is essential for preserving genome integrity. Joining of homologous DNA molecules through strand exchange, a pivotal step in recombination, is mediated by RAD51. Here, we identify RAD51AP1 as a RAD51 accessory protein that specifically stimulates joint molecule formation through the combination of structure-specific DNA binding and physical contact with RAD51. At the cellular level, we show that RAD51AP1 is required to protect cells from the adverse effects of DNA double-strand break-inducing agents. At the biochemical level, we show that RAD51AP1 has a selective affinity for branched-DNA structures that are obligatory intermediates during joint molecule formation. Our results highlight the importance of structural transitions in DNA as control points in recombination. The affinity of RAD51 AP1 for the central protein and DNA intermediates of recombination confers on it the ability to control the preservation of genome integrity at a number of critical mechanistic steps. C1 Erasmus MC, Dept Cell Biol & Genet, NL-3000 CA Rotterdam, Netherlands. Erasmus MC, Dept Biochem & Proteom, NL-3000 CA Rotterdam, Netherlands. Erasmus MC, Dept Radiat Oncol, NL-3000 CA Rotterdam, Netherlands. NIDDK, Natl Inst Hlth, Mol Biol Lab, Bethesda, MD 20892 USA. RP Modesti, M (reprint author), CNRS, FRE 2931, Genome Instabil & Carcinogenesis, 31 Chem Joseph Aiguier, F-13402 Marseille 20, France. EM mmodesti@ibsm.cnrs-mrs.fr RI Ghirlando, Rodolfo/A-8880-2009; OI Demmers, Jeroen/0000-0002-8757-9611; Modesti, Mauro/0000-0002-4964-331X FU Intramural NIH HHS NR 46 TC 48 Z9 49 U1 0 U2 4 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 NOV 9 PY 2007 VL 28 IS 3 BP 468 EP 481 DI 10.1016/j.molcel.2007.08.025 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 229BR UT WOS:000250776800014 PM 17996710 ER PT J AU Zezula, J Rice, KC Hudlicky, T AF Zezula, Josef Rice, Kenner C. Hudlicky, Tomas TI Design for morphine alkaloids by intramolecular heck strategy: Chemoenzymatic synthesis of 10-hydroxy-14-epi-dihydrocodeinone via C-D-B ring construction SO SYNLETT LA English DT Article DE enzymatic dihydroxylation; Heck reaction; Mitsunobu reaction; Friedel-Crafts reaction; morphinans ID RADICAL CYCLIZATION APPROACH; ENANTIOSELECTIVE SYNTHESIS; TRANS-MORPHINE; (-)-MORPHINE; (-)-GALANTHAMINE; STEREOCHEMISTRY; (-)-DIHYDROCODEINONE; DERIVATIVES; ISONEOPINE; CONVERSION AB Enzymatic dihydroxylation of beta-bromoethylbenzene provided a homochiral diene diol that served as starting material for the synthesis of the complete morphinan skeleton via an intramolecular Heck cyclization. C1 Brock Univ, Dept Chem, Ctr Biotechnol, St Catharines, ON L2S 3A1, Canada. Natl Inst Hlth, Dept Hlth & Human Serv, Natl Inst Drug Abuse, Drug Design & Synth Sect,Chem Biol Res Branch, Bethesda, MD 20892 USA. RP Hudlicky, T (reprint author), Brock Univ, Dept Chem, Ctr Biotechnol, 500 Glenridge Ave, St Catharines, ON L2S 3A1, Canada. EM thudlicky@brocku.ca NR 42 TC 14 Z9 14 U1 1 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0936-5214 J9 SYNLETT JI Synlett PD NOV 9 PY 2007 IS 18 BP 2863 EP 2867 DI 10.1055/s-2007-990832 PG 5 WC Chemistry, Organic SC Chemistry GA 239GO UT WOS:000251507000020 ER PT J AU Gopich, IV Szabo, A AF Gopich, Irina V. Szabo, Attila TI Single-molecule FRET with diffusion and conformational dynamics SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID RESONANCE ENERGY-TRANSFER; FLUORESCENCE SPECTROSCOPY; PHOTON STATISTICS; PROTEIN; IDENTIFICATION; DISTRIBUTIONS; HISTOGRAMS; EXCITATION AB Under relatively mild conditions, we show how one can extract information about conformational dynamics from Forster resonance energy transfer (FRET) experiments on diffusing molecules without modeling diffusion. Starting from a rigorous theory that does treat diffusion, we first examine when the single-molecule FRET efficiency distribution can be decomposed into the measured distribution of the total number of photons and the efficiency distribution of an immobilized molecule in the absence of shot noise. If the conformation does not change during the time the molecule spends in the laser spot, this is possible when (I) the efficiency is independent of the location in the laser spot and (II) the total number of photons does not depend on conformation. This decomposition is approximate when the conformation changes during the diffusion time. However, it does provide a simple framework for analyzing data. This is illustrated for a two-state system where the FRET efficiency distribution can be found analytically for all values of the interconversion rates. If the arrival time of each donor and acceptor photon can be monitored, we introduce an alternative procedure that allows one to rigorously extract the rates of conformational changes when the above two conditions hold. In this case, the pattern of colors in the photon trajectory depends solely on conformational dynamics. This can be exploited in the framework of statistical inference because the likelihood function, which must be optimized with respect to the model rate parameters, depends only on how the conformation changes during the interval between photons with specified colors. C1 NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. RP Gopich, IV (reprint author), NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012 FU Intramural NIH HHS NR 32 TC 81 Z9 81 U1 0 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD NOV 8 PY 2007 VL 111 IS 44 BP 12925 EP 12932 DI 10.1021/jp075255e PG 8 WC Chemistry, Physical SC Chemistry GA 227IQ UT WOS:000250650800040 PM 17929964 ER PT J AU Clark, AG Eisen, MB Smith, DR Bergman, CM Oliver, B Markow, TA Kaufman, TC Kellis, M Gelbart, W Iyer, VN Pollard, DA Sackton, TB Larracuente, AM Singh, ND Abad, JP Abt, DN Adryan, B Aguade, M Akashi, H Anderson, WW Aquadro, CF Ardell, DH Arguello, R Artieri, CG Barbash, DA Barker, D Barsanti, P Batterham, P Batzoglou, S Begun, D Bhutkar, A Blanco, E Bosak, SA Bradley, RK Brand, AD Brent, MR Brooks, AN Brown, RH Butlin, RK Caggese, C Calvi, BR de Carvalho, AB Caspi, A Castrezana, S Celniker, SE Chang, JL Chapple, C Chatterji, S Chinwalla, A Civetta, A Clifton, SW Comeron, JM Costello, JC Coyne, JA Daub, J David, RG Delcher, AL Delehaunty, K Do, CB Ebling, H Edwards, K Eickbush, T Evans, JD Filipski, A Findeiss, S Freyhult, E Fulton, L Fulton, R Garcia, ACL Gardiner, A Garfield, DA Garvin, BE Gibson, G Gilbert, D Gnerre, S Godfrey, J Good, R Gotea, V Gravely, B Greenberg, AJ Griffiths-Jones, S Gross, S Guigo, R Gustafson, EA Haerty, W Hahn, MW Halligan, DL Halpern, AL Halter, GM Han, MV Heger, A Hillier, L Hinrichs, AS Holmes, I Hoskins, RA Hubisz, MJ Hultmark, D Huntley, MA Jaffe, DB Jagadeeshan, S Jeck, WR Johnson, J Jones, CD Jordan, WC Karpen, GH Kataoka, E Keightley, PD Kheradpour, P Kirkness, EF Koerich, LB Kristiansen, K Kudrna, D Kulathinal, RJ Kumar, S Kwok, R Lander, E Langley, CH Lapoint, R Lazzaro, BP Lee, SJ Levesque, L Li, RQ Lin, CF Lin, MF Lindblad-Toh, K Llopart, A Long, MY Low, L Lozovsky, E Lu, J Luo, MH Machado, CA Makalowski, W Marzo, M Matsuda, M Matzkin, L McAllister, B McBride, CS McKernan, B McKernan, K Mendez-Lago, M Minx, P Mollenhauer, MU Montooth, K Mount, SM Mu, X Myers, E Negre, B Newfeld, S Nielsen, R Noor, MAF O'Grady, P Pachter, L Papaceit, M Parisi, MJ Parisi, M Parts, L Pedersen, JS Pesole, G Phillippy, AM Ponting, CP Pop, M Porcelli, D Powell, JR Prohaska, S Pruitt, K Puig, M Quesneville, H Ram, KR Rand, D Rasmussen, MD Reed, LK Reenan, R Reily, A Remington, KA Rieger, TT Ritchie, MG Robin, C Rogers, YH Rohde, C Rozas, J Rubenfield, MJ Ruiz, A Russo, S Salzberg, SL Sanchez-Gracia, A Saranga, DJ Sato, H Schaeffer, SW Schatz, MC Schlenke, T Schwartz, R Segarra, C Singh, RS Sirot, L Sirota, M Sisneros, NB Smith, CD Smith, TF Spieth, J Stage, DE Stark, A Stephan, W Strausberg, RL Strempel, S Sturgill, D Sutton, G Sutton, GG Tao, W Teichmann, S Tobari, YN Tomimura, Y Tsolas, JM Valente, VLS Venter, E Venter, JC Vicario, S Vieira, FG Vilella, AJ Villasante, A Walenz, B Wang, J Wasserman, M Watts, T Wilson, D Wilson, RK Wing, RA Wolfner, MF Wong, A Wong, GKS Wu, CI Wu, G Yamamoto, D Yang, HP Yang, SP Yorke, JA Yoshida, K Zdobnov, E Zhang, PL Zhang, Y Zimin, AV Baldwin, J Abdouelleil, A Abdulkadir, J Abebe, A Abera, B Abreu, J Acer, SC Aftuck, L Alexander, A An, P Anderson, E Anderson, S Arachi, H Azer, M Bachantsang, P Barry, A Bayul, T Berlin, A Bessette, D Bloom, T Blye, J Boguslavskiy, L Bonnet, C Boukhgalter, B Bourzgui, I Brown, A Cahill, P Channer, S Cheshatsang, Y Chuda, L Citroen, M Collymore, A Cooke, P Costello, M D'Aco, K Daza, R De Haan, G DeGray, S DeMaso, C Dhargay, N Dooley, K Dooley, E Doricent, M Dorje, P Dorjee, K Dupes, A Elong, R Falk, J Farina, A Faro, S Ferguson, D Fisher, S Foley, CD Franke, A Friedrich, D Gadbois, L Gearin, G Gearin, CR Giannoukos, G Goode, T Graham, J Grandbois, E Grewal, S Gyaltsen, K Hafez, N Hagos, B Hall, J Henson, C Hollinger, A Honan, T Huard, MD Hughes, L Hurhula, B Husby, ME Kamat, A Kanga, B Kashin, S Khazanovich, D Kisner, P Lance, K Lara, M Lee, W Lennon, N Letendre, F LeVine, R Lipovsky, A Liu, XH Liu, JL Liu, ST Lokyitsang, T Lokyitsang, Y Lubonja, R Lui, A MacDonald, P Magnisalis, V Maru, K Matthews, C McCusker, W McDonough, S Mehta, T Meldrim, J Meneus, L Mihai, O Mihalev, A Mihova, T Mittelman, R Mlenga, V Montmayeur, A Mulrain, L Navidi, A Naylor, J Negash, T Nguyen, T Nguyen, N Nicol, R Norbu, C Norbu, N Novod, N O'Neill, B Osman, S Markiewicz, E Oyono, OL Patti, C Phunkhang, P Pierre, F Priest, M Raghuraman, S Rege, F Reyes, R Rise, C Rogov, P Ross, K Ryan, E Settipalli, S Shea, T Sherpa, N Shi, L Shih, D Sparrow, T Spaulding, J Stalker, J Stange-Thomann, N Stavropoulos, S Stone, C Strader, C Tesfaye, S Thomson, T Thoulutsang, Y Thoulutsang, D Topham, K Topping, I Tsamla, T Vassiliev, H Vo, A Wangchuk, T Wangdi, T Weiand, M Wilkinson, J Wilson, A Yadav, S Young, G Yu, Q Zembek, L Zhong, D Zimmer, A Zwirko, Z Jaffe, DB Alvarez, P Brockman, W Butler, J Chin, C Gnerre, S Grabherr, M Kleber, M Mauceli, E MacCallum, I AF Clark, Andrew G. Eisen, Michael B. Smith, Douglas R. Bergman, Casey M. Oliver, Brian Markow, Therese A. Kaufman, Thomas C. Kellis, Manolis Gelbart, William Iyer, Venky N. Pollard, Daniel A. Sackton, Timothy B. Larracuente, Amanda M. Singh, Nadia D. Abad, Jose P. Abt, Dawn N. Adryan, Boris Aguade, Montserrat Akashi, Hiroshi Anderson, Wyatt W. Aquadro, Charles F. Ardell, David H. Arguello, Roman Artieri, Carlo G. Barbash, Daniel A. Barker, Daniel Barsanti, Paolo Batterham, Phil Batzoglou, Serafim Begun, Dave Bhutkar, Arjun Blanco, Enrico Bosak, Stephanie A. Bradley, Robert K. Brand, Adrianne D. Brent, Michael R. Brooks, Angela N. Brown, Randall H. Butlin, Roger K. Caggese, Corrado Calvi, Brian R. de Carvalho, A. Bernardo Caspi, Anat Castrezana, Sergio Celniker, Susan E. Chang, Jean L. Chapple, Charles Chatterji, Sourav Chinwalla, Asif Civetta, Alberto Clifton, Sandra W. Comeron, Josep M. Costello, James C. Coyne, Jerry A. Daub, Jennifer David, Robert G. Delcher, Arthur L. Delehaunty, Kim Do, Chuong B. Ebling, Heather Edwards, Kevin Eickbush, Thomas Evans, Jay D. Filipski, Alan Findeiss, Sven Freyhult, Eva Fulton, Lucinda Fulton, Robert Garcia, Ana C. L. Gardiner, Anastasia Garfield, David A. Garvin, Barry E. Gibson, Greg Gilbert, Don Gnerre, Sante Godfrey, Jennifer Good, Robert Gotea, Valer Gravely, Brenton Greenberg, Anthony J. Griffiths-Jones, Sam Gross, Samuel Guigo, Roderic Gustafson, Erik A. Haerty, Wilfried Hahn, Matthew W. Halligan, Daniel L. Halpern, Aaron L. Halter, Gillian M. Han, Mira V. Heger, Andreas Hillier, LaDeana Hinrichs, Angie S. Holmes, Ian Hoskins, Roger A. Hubisz, Melissa J. Hultmark, Dan Huntley, Melanie A. Jaffe, David B. Jagadeeshan, Santosh Jeck, William R. Johnson, Justin Jones, Corbin D. Jordan, William C. Karpen, Gary H. Kataoka, Eiko Keightley, Peter D. Kheradpour, Pouya Kirkness, Ewen F. Koerich, Leonardo B. Kristiansen, Karsten Kudrna, Dave Kulathinal, Rob J. Kumar, Sudhir Kwok, Roberta Lander, Eric Langley, Charles H. Lapoint, Richard Lazzaro, Brian P. Lee, So-Jeong Levesque, Lisa Li, Ruiqiang Lin, Chiao-Feng Lin, Michael F. Lindblad-Toh, Kerstin Llopart, Ana Long, Manyuan Low, Lloyd Lozovsky, Elena Lu, Jian Luo, Meizhong Machado, Carlos A. Makalowski, Wojciech Marzo, Mar Matsuda, Muneo Matzkin, Luciano McAllister, Bryant McBride, Carolyn S. McKernan, Brendan McKernan, Kevin Mendez-Lago, Maria Minx, Patrick Mollenhauer, Michael U. Montooth, Kristi Mount, Stephen M. Mu, Xu Myers, Eugene Negre, Barbara Newfeld, Stuart Nielsen, Rasmus Noor, Mohamed A. F. O'Grady, Patrick Pachter, Lior Papaceit, Montserrat Parisi, Matthew J. Parisi, Michael Parts, Leopold Pedersen, Jakob S. Pesole, Graziano Phillippy, Adam M. Ponting, Chris P. Pop, Mihai Porcelli, Damiano Powell, Jeffrey R. Prohaska, Sonja Pruitt, Kim Puig, Marta Quesneville, Hadi Ram, Kristipati Ravi Rand, David Rasmussen, Matthew D. Reed, Laura K. Reenan, Robert Reily, Amy Remington, Karin A. Rieger, Tania T. Ritchie, Michael G. Robin, Charles Rogers, Yu-Hui Rohde, Claudia Rozas, Julio Rubenfield, Marc J. Ruiz, Alfredo Russo, Susan Salzberg, Steven L. Sanchez-Gracia, Alejandro Saranga, David J. Sato, Hajime Schaeffer, Stephen W. Schatz, Michael C. Schlenke, Todd Schwartz, Russell Segarra, Carmen Singh, Rama S. Sirot, Laura Sirota, Marina Sisneros, Nicholas B. Smith, Chris D. Smith, Temple F. Spieth, John Stage, Deborah E. Stark, Alexander Stephan, Wolfgang Strausberg, Robert L. Strempel, Sebastian Sturgill, David Sutton, Granger Sutton, Granger G. Tao, Wei Teichmann, Sarah Tobari, Yoshiko N. Tomimura, Yoshihiko Tsolas, Jason M. Valente, Vera L. S. Venter, Eli Venter, J. Craig Vicario, Saverio Vieira, Filipe G. Vilella, Albert J. Villasante, Alfredo Walenz, Brian Wang, Jun Wasserman, Marvin Watts, Thomas Wilson, Derek Wilson, Richard K. Wing, Rod A. Wolfner, Mariana F. Wong, Alex Wong, Gane Ka-Shu Wu, Chung-I Wu, Gabriel Yamamoto, Daisuke Yang, Hsiao-Pei Yang, Shiaw-Pyng Yorke, James A. 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Giannoukos, Georgia Goode, Tina Graham, Joseph Grandbois, Edward Grewal, Sharleen Gyaltsen, Kunsang Hafez, Nabil Hagos, Birhane Hall, Jennifer Henson, Charlotte Hollinger, Andrew Honan, Tracey Huard, Monika D. Hughes, Leanne Hurhula, Brian Husby, M. Erii Kamat, Asha Kanga, Ben Kashin, Seva Khazanovich, Dmitry Kisner, Peter Lance, Krista Lara, Marcia Lee, William Lennon, Niall Letendre, Frances LeVine, Rosie Lipovsky, Alex Liu, Xiaohong Liu, Jinlei Liu, Shangtao Lokyitsang, Tashi Lokyitsang, Yeshi Lubonja, Rakela Lui, Annie MacDonald, Pen Magnisalis, Vasilia Maru, Kebede Matthews, Charles McCusker, William McDonough, Susan Mehta, Teena Meldrim, James Meneus, Louis Mihai, Oana Mihalev, Atanas Mihova, Tanya Mittelman, Rachel Mlenga, Valentine Montmayeur, Anna Mulrain, Leonidas Navidi, Adam Naylor, Jerome Negash, Tamrat Nguyen, Thu Nguyen, Nga Nicol, Robert Norbu, Choe Norbu, Nyima Novod, Nathaniel O'Neill, Barry Osman, Sahal Markiewicz, Eva Oyono, Otero L. Patti, Christopher Phunkhang, Pema Pierre, Fritz Priest, Margaret Raghuraman, Sujaa Rege, Filip Reyes, Rebecca Rise, Cecil Rogov, Peter Ross, Keenan Ryan, Elizabeth Settipalli, Sampath Shea, Terry Sherpa, Ngawang Shi, Lu Shih, Diana Sparrow, Todd Spaulding, Jessica Stalker, John Stange-Thomann, Nicole Stavropoulos, Sharon Stone, Catherine Strader, Christopher Tesfaye, Senait Thomson, Talene Thoulutsang, Yama Thoulutsang, Dawa Topham, Kerri Topping, Ira Tsamla, Tsamla Vassiliev, Helen Vo, Andy Wangchuk, Tsering Wangdi, Tsering Weiand, Michael Wilkinson, Jane Wilson, Adam Yadav, Shailendra Young, Geneva Yu, Qing Zembek, Lisa Zhong, Danni Zimmer, Andrew Zwirko, Zac Jaffe, David B. Alvarez, Pablo Brockman, Will Butler, Jonathan Chin, CheeWhye Gnerre, Sante Grabherr, Manfred Kleber, Michael Mauceli, Evan MacCallum, Iain CA Drosophila 12 Genomes Consor Broad Inst Genome Sequencing Broad Inst Whole Genome Ass TI Evolution of genes and genomes on the Drosophila phylogeny SO NATURE LA English DT Article ID AMINO-ACID SUBSTITUTION; SYNONYMOUS CODON USAGE; ADAPTIVE PROTEIN EVOLUTION; MOLECULAR EVOLUTION; MELANOGASTER GENOME; MAXIMUM-LIKELIHOOD; NATURAL-SELECTION; NONCODING DNA; FRUIT-FLY; DOSAGE COMPENSATION AB Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species. C1 Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. 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Inst Evolutionary Biol, Setagaya Ku, Tokyo 1580098, Japan. Shiba Gakuen, Minato Ku, Tokyo 1050011, Japan. European Bioinformat Inst, Hinxton CB10 1SD, England. CUNY Queens Coll, Dept Biol, Flushing, NY 11367 USA. Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada. Univ Alberta, Dept Med, Edmonton, AB T6G 2E9, Canada. Tohoku Univ, Dept Dev Biol & Neurosci, Sendai, Miyagi 9808578, Japan. Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA. Hokkaido Univ, EESBIO, Sapporo, Hokkaido 0600810, Japan. Univ Geneva, Fac Med, CH-1211 Geneva, Switzerland. RP Clark, AG (reprint author), Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. EM ac347@cornell.edu; mbeisen@lbl.gov; douglas.smith@agencourt.com; gelbart@morgan.harvard.edu; oliver@helix.nih.gov; tmarkow@public.arl.arizona.edu; kaufman@indiana.edu; manoli@mit.edu; venky@berkeley.edu; danielapollard@alum.bowdoin.edu; tbs7@cornell.edu; aml69@cornell.edu; nds25@cornell.edu RI McAllister, Bryant/A-3015-2008; Pedersen, Jakob/C-4985-2009; Vilella, Albert/A-8586-2008; Han, Mira/A-1808-2011; Brooks, Angela/B-6173-2011; Schaeffer, Stephen/B-1662-2010; Nielsen, Rasmus/D-4405-2009; Phelps, Steve/H-2263-2011; Halligan, Daniel/H-4459-2011; Ritchie, Michael/B-7714-2008; Koerich, Leonardo/B-8554-2008; Rozas, Julio/A-1733-2009; Machado, Carlos/B-8855-2009; Stark, Alexander/D-1473-2012; Hultmark, Dan/C-5058-2013; Kristiansen, Karsten/J-5148-2014; Wang, Jun/C-8434-2016; Puig, Marta/F-7885-2016; Makalowski, Wojciech/I-2843-2016; Pedersen, Jakob/G-3382-2012; Pop, Mihai/A-7987-2013; Sanchez-Gracia, Alejandro/F-4686-2014; Wang, Jun/B-9503-2016; Wong, Gane/A-3771-2014; Evans, Jay/C-8408-2012; Pesole, Graziano/E-9051-2014; Griffiths-Jones, Sam/H-2998-2014; Koerich, Leonardo/J-7004-2014; Robin, Charles/F-7786-2010; vicario, saverio/C-4427-2015; Guigo, Roderic/D-1303-2010; Garrett Vieira, Filipe/B-9464-2015; Wong, Gane Ka-Shu/G-5784-2013; Kumar, Sudhir/F-1411-2011; Bergman, Casey/F-7854-2010; Schwartz, Russell/A-1998-2016; Batterham, Philip/G-5914-2012; Comeron, Josep/G-6630-2012; Pesole, Graziano/C-1408-2009; Zdobnov, Evgeny/K-1133-2012; Barker, David/A-5671-2013; Matzkin, Luciano/B-3168-2013; Graveley, Brenton/C-3108-2013; Negre, Barbara/F-2540-2013; Butlin, Roger/F-7709-2013; Marion-Poll, Frederic/D-8882-2011; Carvalho, A. Bernardo/D-5402-2013; Ritchie, Michael/F-7055-2013; Valente, Vera/N-9031-2013; OI Nielsen, Rasmus/0000-0003-0513-6591; Koerich, Leonardo/0000-0002-5668-3934; Rozas, Julio/0000-0002-6839-9148; Machado, Carlos/0000-0003-1546-7415; Stark, Alexander/0000-0003-2611-0841; Hultmark, Dan/0000-0002-6506-5855; Kristiansen, Karsten/0000-0002-6024-0917; Wang, Jun/0000-0002-8540-8931; Puig, Marta/0000-0002-4439-6372; Pedersen, Jakob/0000-0002-7236-4001; Pop, Mihai/0000-0001-9617-5304; Sanchez-Gracia, Alejandro/0000-0003-4543-4577; Mount, Steve/0000-0003-2748-8205; Sackton, Timothy/0000-0003-1673-9216; McKernan, Kevin/0000-0002-3908-1122; Schatz, Michael/0000-0002-4118-4446; Adryan, Boris/0000-0003-4588-7867; Vilella, Albert/0000-0002-2005-2516; Montmayeur, Anna/0000-0002-8132-1716; Wang, Jun/0000-0002-2113-5874; Ravi Ram, Kristipati/0000-0002-7285-0077; Eisen, Michael/0000-0002-7528-738X; Evans, Jay/0000-0002-0036-4651; Pesole, Graziano/0000-0003-3663-0859; Griffiths-Jones, Sam/0000-0001-6043-807X; Robin, Charles/0000-0002-7733-6763; vicario, saverio/0000-0003-1140-0483; Guigo, Roderic/0000-0002-5738-4477; Garrett Vieira, Filipe/0000-0002-8464-7770; Wong, Gane Ka-Shu/0000-0001-6108-5560; Bergman, Casey/0000-0002-5462-9854; Schwartz, Russell/0000-0002-4970-2252; Batterham, Philip/0000-0001-9840-9119; Pesole, Graziano/0000-0003-3663-0859; Negre, Barbara/0000-0002-7333-3979; Butlin, Roger/0000-0003-4736-0954; Marion-Poll, Frederic/0000-0001-6824-0180; Carvalho, A. Bernardo/0000-0001-8959-6469; Ritchie, Michael/0000-0001-7913-8675; Schaeffer, Stephen/0000-0003-2070-5342; Teichmann, Sarah/0000-0002-6294-6366; Bradley, Robert/0000-0002-8046-1063; Salzberg, Steven/0000-0002-8859-7432; Hinrichs, Angie/0000-0002-1697-1130; Noor, Mohamed/0000-0002-5400-4408; Haerty, Wilfried/0000-0003-0111-191X; Ponting, Chris/0000-0003-0202-7816; Wing, Rod/0000-0001-6633-6226; Segarra, Carmen/0000-0002-3201-5405; Heger, Andreas/0000-0001-7720-0447; Holmes, Ian/0000-0001-7639-5369; Gotea, Valer/0000-0001-7857-3309 NR 151 TC 960 Z9 3043 U1 32 U2 313 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD NOV 8 PY 2007 VL 450 IS 7167 BP 203 EP 218 DI 10.1038/nature06341 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 228RC UT WOS:000250746200042 ER PT J AU Zhang, Y Sturgill, D Parisi, M Kumar, S Oliver, B AF Zhang, Yu Sturgill, David Parisi, Michael Kumar, Sudhir Oliver, Brian TI Constraint and turnover in sex-biased gene expression in the genus Drosophila SO NATURE LA English DT Article ID RNA-POLYMERASE-II; EVOLUTIONARY SIGNIFICANCE; MELANOGASTER; MUTATION; GENOME; RATES; ACCUMULATION; DIVERGENCE; SELECTION; PROFILES AB Both genome content and deployment contribute to phenotypic differences between species(1-5). Sex is the most important difference between individuals in a species and has long been posited to be rapidly evolving. Indeed, in the Drosophila genus, traits such as sperm length, genitalia, and gonad size are the most obvious differences between species(6). Comparative analysis of sex-biased expression should deepen our understanding of the relationship between genome content and deployment during evolution. Using existing(7,8) and newly assembled genomes(9), we designed species-specific microarrays to examine sex-biased expression of orthologues and species-restricted genes in D. melanogaster, D. simulans, D. yakuba, D. ananassae, D. pseudoobscura, D. virilis and D. mojavensis. We show that averaged sex-biased expression changes accumulate monotonically over time within the genus. However, different genes contribute to expression variance within species groups compared to between groups. We observed greater turnover of species-restricted genes with male-biased expression, indicating that gene formation and extinction may play a significant part in species differences. Genes with male-biased expression also show the greatest expression and DNA sequence divergence. This higher divergence and turnover of genes with male-biased expression may be due to high transcription rates in the male germline, greater functional pleiotropy of genes expressed in females, and/or sexual competition. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. Arizona State Univ, Ctr Evolutionary Funct Genom, Biodesign Inst, Tempe, AZ 85287 USA. RP Zhang, Y (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM yuzhang@mail.nih.gov; oliver@helix.nih.gov RI Kumar, Sudhir/F-1411-2011 FU Intramural NIH HHS [Z01 DK015600-12]; NHGRI NIH HHS [R01 HG002516, R01 HG002516-04A1] NR 39 TC 161 Z9 162 U1 0 U2 36 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 8 PY 2007 VL 450 IS 7167 BP 233 EP U2 DI 10.1038/nature06323 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 228RC UT WOS:000250746200044 PM 17994089 ER PT J AU Sturgill, D Zhang, Y Parisi, M Oliver, B AF Sturgill, David Zhang, Yu Parisi, Michael Oliver, Brian TI Demasculinization of X chromosomes in the Drosophila genus SO NATURE LA English DT Article ID SEX-BIASED GENES; EXPRESSION; EVOLUTION; INACTIVATION; ELEGANS AB X chromosomes evolve differently from autosomes, but general governing principles have not emerged(1). For example, genes with male-biased expression are under-represented on the X chromosome of D. melanogaster(2), but are randomly distributed in the genome of Anopheles gambiae(3). In direct global profiling experiments using species-specific microarrays, we find a nearly identical paucity of genes with male-biased expression on D. melanogaster, D. simulans, D. yakuba, D. ananassae, D. virilis and D. mojavensis X chromosomes. We observe the same under-representation on the neo-X of D. pseudoobscura. It has been suggested that precocious meiotic silencing of the X chromosome accounts for reduced X chromosome male-biased expression in nematodes(4), mammals(5) and Drosophila(6). We show that X chromosome genes with male-biased expression are under-represented in somatic cells and in mitotic male germ cells. These data are incompatible with simple X chromosome inactivation models. Using expression profiling and comparative sequence analysis, we show that selective gene extinction on the X chromosome, creation of new genes on autosomes and changed genomic location of existing genes contribute to the unusual X chromosome gene content. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Sturgill, D (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM davidsturgill@niddk.nih.gov; oliver@helix.nih.gov FU Intramural NIH HHS [Z01 DK015600-12] NR 25 TC 139 Z9 139 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 8 PY 2007 VL 450 IS 7167 BP 238 EP U3 DI 10.1038/nature06330 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 228RC UT WOS:000250746200045 PM 17994090 ER PT J AU Gore, AV Cheong, A Gilligan, PC Sampath, K AF Gore, Aniket V. Cheong, Albert Gilligan, Patrick C. Sampath, Karuna TI Maternal nodal and zebrafish embryogenesis - Reply SO NATURE LA English DT Letter ID MESENDODERM; RECEPTOR; GENES; LAYER C1 Natl Univ Singapore, Temasek Life Sci Lab, Vertebrate Dev Grp, Singapore 117604, Singapore. Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore. Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore. RP Gore, AV (reprint author), NICHHD, Unit Vertebrate Organogenesis, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM karuna@tll.org.sg NR 15 TC 7 Z9 7 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 8 PY 2007 VL 450 IS 7167 BP E2 EP E4 DI 10.1038/nature06315 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 228RC UT WOS:000250746200047 ER PT J AU Bellanger, S de Gramont, A Sobczak-Thepot, J AF Bellanger, S. de Gramont, A. Sobczak-Thepot, J. TI Cyclin B2 suppresses mitotic failure and DNA re-replication in human somatic cells knocked down for both cyclins B1 and B2 SO ONCOGENE LA English DT Article DE cyclin; mitosis; RNA interference; replication; cell cycle ID DEPENDENT KINASES; MAMMALIAN-CELLS; GEMININ BINDING; TUMOR-CELLS; IN-VITRO; PHOSPHORYLATION; MITOSIS; B1; LOCALIZATION; INHIBITOR AB Cyclin-dependent kinase 1 (CDK1) plays a crucial role in establishing metaphase and has also been shown to prevent DNA re-replication. Cyclins B1 and B2 are two known activators of CDK1 operating during mitosis in human cells. Little is known about the specific roles of each of these cyclins in CDK1 activation, but cyclin B2 is thought to play a minor role and to be unable to replace cyclin B1 for mitosis completion. In our study, we found that severe reduction by separate RNA interference of either cyclin B1 or cyclin B2 protein levels results in little or no alteration of the cell cycle and, more specifically, of mitosis progression. In contrast, simultaneous depletion of both B-type cyclins leads to massive accumulation of 4N cells, mitotic failure, premature mitosis exit and DNA re-replication. These defects can be corrected by the ectopic expression of a cyclin B2 resistant to the short hairpin RNA. Altogether, these data show that, in cycling human cells, cyclin B2 can compensate for the downregulation of cyclin B1 during mitosis. They also clearly implicate cyclins B1 and B2 as crucial activators of CDK1 in its biological function of DNA re-replication prevention. C1 Univ Paris 06, CNRS, UMR 7098, Biochim Cellulaire Lab, F-75005 Paris, France. Inst Med Biol, Singapore 138673, Singapore. NIH, NIDDK, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP Sobczak-Thepot, J (reprint author), Univ Paris 06, CNRS, UMR 7098, Biochim Cellulaire Lab, F-75005 Paris, France. EM Joelle.Sobczak-Thepot@snv.jussieu.fr NR 36 TC 28 Z9 29 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 8 PY 2007 VL 26 IS 51 BP 7175 EP 7184 DI 10.1038/sj.onc.1210539 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 231NO UT WOS:000250955600001 PM 17533373 ER PT J AU Li, W Xiao, C Vonderhaar, BK Deng, CX AF Li, W. Xiao, C. Vonderhaar, B. K. Deng, C-X TI A role of estrogen/ER alpha signaling in BRCA1-associated tissue-specific tumor formation SO ONCOGENE LA English DT Article DE ERK1/2; cyclin D1; ER alpha; BRCA1; mammary tumors ID BREAST-CANCER; CELL-CYCLE; BRCA2 MUTATIONS; OVARIAN-CANCER; RECEPTOR; SUSCEPTIBILITY; WOMEN; MICE; TUMORIGENESIS; OOPHORECTOMY AB Estrogen and its receptor alpha (ER alpha) have been implicated in the tissue-specific tumorigenesis associated with BRCA1 mutations. However, the majority of breast cancers developed in human BRCA1 mutation carriers are ER alpha-negative, challenging the link between BRCA1 and estrogen/ER alpha in breast cancer formation. Using a mouse model lacking the full-length form of BRCA1, here we show that ERa is highly expressed in the premalignant mammary gland and initiation stages of tumorigenesis, although its expression is gradually diminished during mammary tumor progression. We demonstrate that the absence of full-length BRCA1 increases sensitivity of cells to estrogen-induced extracellular signal-regulated kinase 1/2 phosphorylation and cyclin D1 expression. The absence of BRCA1 turns the proliferation of ER alpha-positive cells from a paracrine fashion to an autocrine or endocrine fashion. Consequently, BRCA1-mutant cells are sensitized to estrogen-induced cell proliferation in vitro and mammary tumorigenesis in vivo. These findings illustrate a molecular mechanism for estrogen/ER alpha signals in BRCA1-associated tissue-specific tumor formation, and identify several key elements in the estrogen/ER alpha-signaling cascade that can serve as potential therapeutic targets for BRCA1-associated tumorigenesis. C1 Natl Inst Hlth, NIDDK, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. Natl Inst Hlth, Natl Canc Inst, Mammary Biol & Tumorigen Lab, Bethesda, MD USA. RP Deng, CX (reprint author), Natl Inst Hlth, NIDDK, Genet Dev & Dis Branch, 10-9N105, 10 Ctr Dr, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 34 TC 29 Z9 30 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 8 PY 2007 VL 26 IS 51 BP 7204 EP 7212 DI 10.1038/sj.onc.1210527 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 231NO UT WOS:000250955600004 PM 17496925 ER PT J AU Beck, S Taube, W Gruber, M Amtage, F Gollhofer, A Schubert, M AF Beck, S. Taube, W. Gruber, M. Amtage, F. Gollhofer, A. Schubert, M. TI Task-specific changes in motor evoked potentials of lower limb muscles after different training interventions SO BRAIN RESEARCH LA English DT Article DE training; plasticity; motor evoked potentials; cortico-spinal tract ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN GAIT; FORCE DEVELOPMENT; STRETCH REFLEXES; SOLEUS MUSCLE; CORTEX; MODULATION; HUMANS; ACTIVATION; PLASTICITY AB This study aimed to identify sites and mechanisms of long-term plasticity following lower limb muscle training. Two groups performing either a postural stability maintenance training (SMT) or a ballistic ankle strength training (BST) were compared to a non-training group. The hypothesis was that practicing of a self-initiated voluntary movement would facilitate cortico-spinal projections, while practicing fast automatic adjustments during stabilization of stance would reduce excitatory influence from the primary motor cortex. Training effects were expected to be confined to the practiced task. To test for training specificity, motor evoked potentials (MEP) induced by transcranial magnetic stimulation (TMS) were recorded at rest and during motor tasks that were similar to each training. Intracortical, cortico-spinal, as well as spinal parameters were assessed at rest and during these tasks. The results show high task and training specificity. Training effects were only observable during performance of the trained task. While MEP size was decreased in the SMT group for the trained tasks, MEP recruitment was increased in the BST group in the trained task only. The control group did not show any changes. Background electromyogram levels, M. soleus H-reflex amplitudes and intracortical parameters were unaltered. In summary, it is suggested that the changes of MEP parameters in both training groups, but not in the control group, reflect cortical motor plasticity. While cortico-spinal activation was enhanced in the BST group, SMT may be associated with improved motor control through increased inhibitory trans-cortical effects. Since spinal excitability remained unaltered, changes most likely occur on the supraspinal level. (c) 2007 Elsevier B.V. All rights reserved. C1 Natl Inst Hlth, NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. Univ Freiburg, Dept Clin Neurol & Neurophysiol, Freiburg, Germany. Univ Freiburg, Dept Sport Sci, Freiburg, Germany. RP Beck, S (reprint author), Natl Inst Hlth, NINDS, Human Motor Control Sect, Bldg 10 5N240, 10 Dr, Bethesda, MD 20892 USA. EM becksa@ninds.nih.gov RI Taube, Wolfgang/E-4018-2012 OI Taube, Wolfgang/0000-0002-8802-2065 NR 42 TC 65 Z9 65 U1 2 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD NOV 7 PY 2007 VL 1179 BP 51 EP 60 DI 10.1016/j.brainres.2007.08.048 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 235CD UT WOS:000251210200006 PM 17889840 ER PT J AU Iversen, ES Katki, HA Chen, S Berry, DA Parmigiani, G AF Iversen, Edwin S., Jr. Katki, Hormuzd A. Chen, Sining Berry, Donald A. Parmigiani, Giovanni TI Limited family structure and breast cancer risk SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 Duke Univ, Dept Stat Sci, Durham, NC 27706 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Iversen, ES (reprint author), Duke Univ, Dept Stat Sci, Durham, NC 27706 USA. EM iversen@stat.duke.edu RI Katki, Hormuzd/B-4003-2015 NR 4 TC 1 Z9 1 U1 0 U2 1 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 NOV 7 PY 2007 VL 298 IS 17 BP 2007 EP 2007 DI 10.1001/jama.298.17.2007-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 228GP UT WOS:000250718200018 PM 17986693 ER PT J AU Flegal, KM Graubard, BI Williamson, DF Gail, MH AF Flegal, Katherine M. Graubard, Barry I. Williamson, David F. Gail, Mitchell H. TI Cause-specific excess deaths associated with underweight, overweight, and obesity SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BODY-MASS INDEX; OBSTRUCTIVE PULMONARY-DISEASE; CAUSE-SPECIFIC MORTALITY; AIR-FLOW OBSTRUCTION; MIDDLE-AGED MEN; US ADULTS; FOLLOW-UP; CANCER-MORTALITY; HEART-FAILURE; COHORT AB Context The association of body mass index (BMI) with cause-specific mortality has not been reported for the US population. Objective To estimate cause-specific excess deaths associated with underweight (BMI < 18.5), overweight (BMI 25- <30), and obesity (BMI >= 30). Design, Setting, and Participants Cause-specific relative risks of mortality from the National Health and Nutrition Examination Survey (NHANES) I, 1971-1975; II, 19761980; and III, 1988-1994, with mortality follow-up through 2000 (571 042 person-years of follow-up) were combined with data on BMI and other covariates from NHANES 1999-2002 with underlying cause of death information for 2.3 million adults 25 years and older from 2004 vital statistics data for the United States. Main Outcome Measures Cause-specific excess deaths in 2004 by BMI levels for categories of cardiovascular disease (CVD), cancer, and all other causes (noncancer, non-CVD causes). Results Based on total follow-up, underweight was associated with significantly increased mortality from noncancer, non-CVD causes (23 455 excess deaths; 95% confidence interval [CI], 11 848 to 35 061) but not associated with cancer or CVD mortality. Overweight was associated with significantly decreased mortality from noncancer, non-CVD causes (-69 299 excess deaths; 95% CI, -100 702 to -37 897) but not associated with cancer or CVD mortality. Obesity was associated with significantly increased CVD mortality (112 159 excess deaths; 95% CI, 87 842 to 136 476) but not associated with cancer mortality or with noncancer, non-CVD mortality. In further analyses, overweight and obesity combined were associated with increased mortality from diabetes and kidney disease (61 248 excess deaths; 95% CI, 49 685 to 72 811) and decreased mortality from other noncancer, non-CVD causes (-105 572 excess deaths; 95% CI, -161 816 to -49 328). Obesity was associated with increased mortality from cancers considered obesity-related (13 839 excess deaths; 95% CI, 1920 to 25 758) but not associated with mortality from other cancers. Comparisons across surveys suggested a decrease in the association of obesity with CVD mortality over time. Conclusions The BMI-mortality association varies by cause of death. These results help to clarify the associations of BMI with all-cause mortality. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. RP Flegal, KM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 3311 Toledo Rd,Room 4201, Hyattsville, MD 20782 USA. EM kmf2@cdc.gov RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 55 TC 746 Z9 772 U1 2 U2 50 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 NOV 7 PY 2007 VL 298 IS 17 BP 2028 EP 2037 DI 10.1001/jama.298.17.2028 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 228GP UT WOS:000250718200023 PM 17986696 ER PT J AU Coresh, J Selvin, E Stevens, LA Manzi, J Kusek, JW Eggers, P Van Lente, F Levey, AS AF Coresh, Josef Selvin, Elizabeth Stevens, Lesley A. Manzi, Jane Kusek, John W. Eggers, Paul Van Lente, Frederick Levey, Andrew S. TI Prevalence of chronic kidney disease in the United States SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE VALUES; STAGE RENAL-DISEASE; CARDIOVASCULAR-DISEASE; RISK-FACTORS; US ADULTS; OUTCOMES; HYPERTENSION; AWARENESS; EQUATION AB Context The prevalence and incidence of kidney failure treated by dialysis and transplantation in the United States have increased from 1988 to 2004. Whether there have been changes in the prevalence of earlier stages of chronic kidney disease (CKD) during this period is uncertain. Objective To update the estimated prevalence of CKD in the United States. Design, Setting, and Participants Cross-sectional analysis of the most recent National Health and Nutrition Examination Surveys (NHANES 1988-1994 and NHANES 1999-2004), a nationally representative sample of noninstitutionalized adults aged 20 years or older in 1988-1994 (n = 15 488) and 1999-2004 (n = 13 233). Main Outcome Measures Chronic kidney disease prevalence was determined based on persistent albuminuria and decreased estimated glomerular filtration rate (GFR). Persistence of microalbuminuria (> 30 mg/g) was estimated from repeat visit data in NHANES 1988-1994. The GFR was estimated using the abbreviated Modification of Diet in Renal Disease Study equation reexpressed to standard serum creatinine. Results The prevalence of both albuminuria and decreased GFR increased from 1988-1994 to 1999-2004. The prevalence of CKD stages 1 to 4 increased from 10.0% (95% confidence interval [CI], 9.2%-10.9%) in 1988-1994 to 13.1% (95% CI, 12.0%-14.1%) in 1999-2004 with a prevalence ratio of 1.3 (95% CI, 1.2-1.4). The prevalence estimates of CKD stages in 1988-1994 and 1999-2004, respectively, were 1.7% (95% CI, 1.3%-2.2%) and 1.8% (95% CI, 1.4%-2.3%) for stage 1; 2.7% (95% CI, 2.2%3.2%) and 3.2% (95% CI, 2.6%-3.9%) for stage 2; 5.4% (95% CI, 4.9%-6.0%) and 7.7% (95% CI, 7.0%-8.4%) for stage 3; and 0.21% (95% CI, 0.15%-0.27%) and 0.35% (0.25%-0.45%) for stage 4. A higher prevalence of diagnosed diabetes and hypertension and higher body mass index explained the entire increase in prevalence of albuminuria but only part of the increase in the prevalence of decreased GFR. Estimation of GFR from serum creatinine has limited precision and a change in mean serum creatinine accounted for some of the increased prevalence of CKD. Conclusions The prevalence of CKD in the United States in 1999-2004 is higher than it was in 1988-1994. This increase is partly explained by the increasing prevalence of diabetes and hypertension and raises concerns about future increased incidence of kidney failure and other complications of CKD. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21287 USA. Tufts Univ New England Med Ctr, Div Nephrol, Boston, MA USA. NIDDKD, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Clin Pathol, Cleveland, OH 44195 USA. RP Coresh, J (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 2024 E Monument,Ste 2-600, Baltimore, MD 21287 USA. EM coresh@jhu.edu FU NIDDK NIH HHS [UO1 DK 053869, K01 DK076595, K01 DK076595-01, UO1 DK 067651, UO1 DK 35073] NR 33 TC 2411 Z9 2529 U1 16 U2 123 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 NOV 7 PY 2007 VL 298 IS 17 BP 2038 EP 2047 DI 10.1001/jama.298.17.2038 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 228GP UT WOS:000250718200024 PM 17986697 ER PT J AU Gregg, EW Guralnik, JM AF Gregg, Edward W. Guralnik, Jack M. TI Is disability obesity's price of longevity? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID DISEASE RISK-FACTORS; UNITED-STATES; LIFE EXPECTANCY; TRENDS; ADULTS; 21ST-CENTURY; OVERWEIGHT; ARTHRITIS; DEATHS C1 Ctr Dis Control & Prevent, US PHS, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Gregg, EW (reprint author), Ctr Dis Control & Prevent, US PHS, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Hwy NE,Mailstop K-10, Atlanta, GA 30341 USA. EM edg7@cdc.gov FU Intramural NIH HHS NR 25 TC 19 Z9 19 U1 0 U2 3 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 NOV 7 PY 2007 VL 298 IS 17 BP 2066 EP 2067 DI 10.1001/jama.298.17.2066 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 228GP UT WOS:000250718200030 PM 17986703 ER PT J AU Tricoire, L Del Rio, CAC AF Tricoire, Ludovic Del Rio, Christian Andres Cea- TI Illuminating cholinergic microcircuits in the neocortex SO JOURNAL OF NEUROSCIENCE LA English DT Editorial Material ID INTERNEURONS; NEURONS; RAT; EXCITATION; CORTEX C1 NICHHD, NIH, Lab Cellualr & Synapt Neurophysiol, Bethesda, MD 20892 USA. Univ Valparaiso, Ctr Neurociencias Valparaiso, Valparaiso 2340000, Chile. RP Tricoire, L (reprint author), NICHHD, NIH, Lab Cellualr & Synapt Neurophysiol, 35 Lincoln Dr, Bethesda, MD 20892 USA. EM tricolud@mail.nih.gov; ceadelrc@mail.nih.gov FU Intramural NIH HHS NR 9 TC 2 Z9 2 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 7 PY 2007 VL 27 IS 45 BP 12119 EP 12120 DI 10.1523/JNEUROSCI.3856-07.2007 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 228UR UT WOS:000250758600001 PM 17989276 ER PT J AU Iizuka, Y Sei, Y Weinberger, DR Straub, RE AF Iizuka, Yukihiko Sei, Yoshitatsu Weinberger, Daniel R. Straub, Richard E. TI Evidence that the BLOC-1 protein dysbindin modulates dopamine D-2 receptor internalization and signaling but not D-1 internalization SO JOURNAL OF NEUROSCIENCE LA English DT Article DE DTNBP1; dysbindin; MUTED; BLOC-1; dopamine D-2 receptor; DRD2; dopamine D-1 receptor; DRD1; internalization; endocytosis; CREB; schizophrenia ID LYSOSOME-RELATED ORGANELLES; HERMANSKY-PUDLAK-SYNDROME; PREFRONTAL CORTEX; SCHIZOPHRENIC-PATIENTS; D2 RECEPTORS; NORMAL BRAIN; DTNBP1; BINDING; GENE; OVEREXPRESSION AB The schizophrenia susceptibility gene dystrobrevin-binding protein 1 (DTNBP1) encodes dysbindin, which along with its binding partner Muted is an essential component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1). Dysbindin expression is reduced in schizophrenic brain tissue, but the molecular mechanisms by which this contributes to pathogenesis and symptomatology are unknown. We studied the effects of transfection of DTNBP1 siRNA on cell surface levels of dopamine D-2 receptor (DRD2) in human SH-SY5Y neuroblastoma cells and in rat primary cortical neurons. DTNBP1 siRNA decreased dysbindin protein, increased cell surface DRD2 and blocked dopamine-induced DRD2 internalization. MUTED siRNA produced similar effects. In contrast, decreased dysbindin did not change dopamine D-1. receptor (DRD1) levels, or its basal or dopamine-induced internalization. The DRD2 agonist quinpirole reduced phosphorylation of CREB (cAMP response element-binding protein) in dysbindin downregulated cells, demonstrating enhanced intracellular signaling caused by the upregulation of DRD2. This is the first demonstration of a schizophrenia susceptibility gene exerting a functional effect on DRD2 signaling, a pathway that has long been implicated in the illness. We propose a molecular mechanism for pathogenesis in which risk alleles in DTNBP1, or other factors that also downregulate dysbindin, compromise the ability of BLOC-1 to traffic DRD2 toward degradation, but has little effect on DRD1 trafficking. Impaired trafficking of DRD2 decreases dopamine-induced internalization, and with more receptors retained on the cell surface, dopamine stimulation produces excess intracellular signaling. Such an increase in DRD2 signaling relative to DRD1 would contribute to the imbalances in dopaminergic neurotransmission characteristic of schizophrenia. C1 US Dept Hlth & Human Serv, Natl Inst Mental Hlth Intramural Res Program, Genes Cognit & Psycosis Program, Clin Brain Disorders Branch,NIH, Bethesda, MD 20892 USA. RP Straub, RE (reprint author), US Dept Hlth & Human Serv, Natl Inst Mental Hlth Intramural Res Program, Genes Cognit & Psycosis Program, Clin Brain Disorders Branch,NIH, 10 Ctr Drive Bldg 10,Room 4D18, Bethesda, MD 20892 USA. EM straubr@intra.nimh.nih.gov FU Intramural NIH HHS NR 46 TC 85 Z9 90 U1 3 U2 5 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 NOV 7 PY 2007 VL 27 IS 45 BP 12390 EP 12395 DI 10.1523/JNEUROSCI.1689-07.2007 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 228UR UT WOS:000250758600028 PM 17989303 ER PT J AU Bhattacharjee, S Deterding, LJ Jiang, J Bonini, MG Tomer, KB Ramirez, DC Mason, RP AF Bhattacharjee, Suchandra Deterding, Leesa J. Jiang, JinJie Bonini, Marcelo G. Tomer, Kenneth B. Ramirez, Dario C. Mason, Ronald P. TI Electron transfer between a tyrosyl radical and a cysteine residue in hemoproteins: Spin trapping analysis SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SPERM-WHALE MYOGLOBIN; LOW-DENSITY-LIPOPROTEIN; HYDROGEN-PEROXIDE; PROTEIN RADICALS; MASS-SPECTROMETRY; CYTOCHROME-C; PEROXYNITRITE OXIDATION; THYROID PEROXIDASE; REACTIVE OXYGEN; NITRIC-OXIDE AB We investigated electron transfer between a tyrosyl radical and cysteine residue in two systems, oxyhemoglobin (oxyHb)/peroxynitrite/5,5-dimethyl-1-pyrroline N-oxide (DMPO) and myoglobin (Mb)/hydrogen peroxide/DMPO, using a combination of techniques including ESR, immuno-spin trapping (IST), and ESI/ MS. These techniques show that the nitrone spin trap DMPO covalently binds to one or more amino acid radicals in the protein. Treating oxyHb with peroxynitrite and Mb with H2O2 in the presence of a low DMPO concentration yielded secondary Cys-DMPO radical adduct exclusively, whereas in the presence of high DMPO, more of the primary Tyr-DMPO radical adduct was detected. In both systems studied, we found that, at high DMPO concentrations, mainly tyrosyl radicals (Hb-Tyr(42)/Tyr(24) and Mb-Tyr(103)) are trapped and the secondary electron-transfer reaction does not compete, whereas in the presence of low concentrations of DMPO, the secondary reaction predominates over tyrosyl trapping, and a thiyl radical is formed and then trapped (Hb-Cys(93) or Mb-Cys(110)). With increasing concentrations of DMPO in the reaction medium, primary radicals have an increasing probability of being trapped. MS/MS was used to identify the specific Tyr and Cys residues forming radicals in the myoglobin system. All data obtained from this combination of approaches support the conclusion that the initial site of radical formation is a Tyr, which then abstracts an electron from a cysteine residue to produce a cysteinyl radical. This complex phenomenon of electron transfer from one radical to another has been investigated in proteins by IST, ESR, and MS. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Bhattacharjee, S (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM bhattac1@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013; RAMIREZ, DARIO/K-3312-2013 OI RAMIREZ, DARIO/0000-0001-6725-3326 FU Intramural NIH HHS NR 57 TC 46 Z9 46 U1 2 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 7 PY 2007 VL 129 IS 44 BP 13493 EP 13501 DI 10.1021/ja073349w PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 229QM UT WOS:000250819200035 PM 17939657 ER PT J AU Davis, CD Dwyer, JT AF Davis, Cindy D. Dwyer, Johanna T. TI The "sunshine vitamin": Benefits beyond bone? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID COLORECTAL-CANCER PREVENTION; COLON-CANCER; 25-HYDROXYVITAMIN-D LEVELS; SURVIVAL; 1-ALPHA,25-DIHYDROXYVITAMIN-D-3; METAANALYSIS; RADIATION; NORWAY; CELLS; RISK C1 NIH, NCI, Nutr Sci Res Grp, Bethesda, MD 20892 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. RP Dwyer, JT (reprint author), NIH, Off Dietary Supplements, 6100 Exec Blvd,MSC7517 Room 3B01, Bethesda, MD 20892 USA. EM Dwyerj1@od.nih.gov OI Dwyer, Johanna/0000-0002-0783-1769 NR 26 TC 16 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 7 PY 2007 VL 99 IS 21 BP 1563 EP U5 DI 10.1093/jnci/djm211 PG 3 WC Oncology SC Oncology GA 233DY UT WOS:000251071800003 PM 17971523 ER PT J AU Szabo, E AF Szabo, Eva TI Proliferative changes in chemoprevention trials: Learning from secondary endpoints SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID LUNG EPITHELIAL PROLIFERATION; FORMER SMOKERS; BREAST-CANCER; PREVENTION; TAMOXIFEN; SMOKING C1 NCI, Div Canc Prevent, Lung Upper Aerodigest Canc Res Grp, Rockville, MD 20852 USA. RP Szabo, E (reprint author), NCI, Div Canc Prevent, Lung Upper Aerodigest Canc Res Grp, Room 2137,6130 Execut Blvd, Rockville, MD 20852 USA. EM szaboe@mail.nih.gov NR 15 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 7 PY 2007 VL 99 IS 21 BP 1565 EP 1567 DI 10.1093/jnci/djm206 PG 3 WC Oncology SC Oncology GA 233DY UT WOS:000251071800004 PM 17971524 ER PT J AU Freedman, DM Looker, AC Chang, SC Graubard, BI AF Freedman, D. Michal Looker, Anne C. Chang, Shih-Chen Graubard, Barry I. TI Prospective study of serum vitamin D and cancer mortality in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NON-HODGKINS-LYMPHOMA; COLON-CANCER; ULTRAVIOLET-RADIATION; PROSTATE-CANCER; BREAST-CANCER; COLORECTAL-CANCER; SOLAR-RADIATION; SUBSEQUENT RISK; D METABOLITES; SUNLIGHT AB Background Vitamin D has been hypothesized to reduce cancer mortality through its effects on incidence and/or survival. Epidemiologic studies of the association of 25-hydroxyvitamin D [25(OH)D] and the risk of cancer, however, have been largely limited to incident cancers at a few sites. Methods A total of 16818 participants in the Third National Health and Nutrition Examination Survey who were 17 years or older at enrollment were followed from 1988-1994 through 2000. Levels of serum 25(OH)D were measured at baseline by radioimmunoassay. Cox proportional hazards regression models were used to examine the relationship between serum 25(OH)D levels and total cancer mortality (in the entire population or according to race/ethnicity, sex, age, and retinol status) and mortality from specific cancers. Because serum was collected in the south in cooler months and the north in warmer months, we examined associations by collection season. All statistical tests were two-sided. Results We identified 536 cancer deaths in 146578 person-years. Total cancer mortality was unrelated to baseline vitamin D status in the entire population, men, women, non-Hispanic whites, non-Hispanic blacks, Mexican Americans, and in persons younger than 70 or 70 years or older. We found no interaction between vitamin D and season or vitamin D and serum retinol. Colorectal cancer mortality was inversely related to serum 25(OH)D level, with levels 80 nmol/L or higher associated with a 72% risk reduction (95% confidence interval = 32% to 89%) compared with lower than 50 nmol/L, P-trend = .02. Conclusions Our results do not support an association between 25(OH)D and total cancer mortality, although there was an inverse relationship between 25(OH)D levels and colorectal cancer mortality. C1 NIH, NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Freedman, DM (reprint author), NIH, NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Execut Pl S Rm 7036,6120 Execut Blvd, Bethesda, MD 20892 USA. EM mf101e@nih.gov FU Intramural NIH HHS NR 47 TC 209 Z9 216 U1 1 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 7 PY 2007 VL 99 IS 21 BP 1594 EP 1602 DI 10.1093/jnci/djm204 PG 9 WC Oncology SC Oncology GA 233DY UT WOS:000251071800011 PM 17971526 ER PT J AU Chaturvedi, AK Engels, EA Gilbert, ES Chen, BE Storm, H Lynch, CF Hall, P Langmark, F Pukkala, E Kaijser, M Andersson, M Fossa, SD Joensuu, H Boice, JD Kleinerman, RA Travis, LB AF Chaturvedi, Anil K. Engels, Eric A. Gilbert, Ethel S. Chen, Bingshu E. Storm, Hans Lynch, Charles F. Hall, Per Langmark, Froydis Pukkala, Eero Kaijser, Magnus Andersson, Michael Fossa, Sophie D. Joensuu, Heikki Boice, John D. Kleinerman, Ruth A. Travis, Lois B. TI Second cancers among 104,760 survivors of cervical cancer: Evaluation of long-term risk SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN-PAPILLOMAVIRUS; MALIGNANT NEOPLASMS; COLORECTAL-CANCER; HODGKINS-DISEASE; RADIOTHERAPY; REGISTRIES; COFACTORS; SMOKING AB Background Given the extended survival of patients diagnosed with cervical cancer, the large number of these women treated with radiotherapy, and the presence in this population of established cancer risk factors such as human papillomavirus (HPV) infection and cigarette smoking, it is important to clarify long-term trends in second cancer risk. Methods Using data from 104760 one-year survivors of cervical cancer reported to 13 population-based cancer registries in Denmark, Finland, Norway, Sweden, and the United States, we calculated standardized incidence ratios (SIRs) for second cancers overall and cancers at particular sites among women with cervical cancer, including cervical cancer patients who were treated or not treated with radiation, over more than 40 years of follow-up. Cox regression models were used to assess the time-varying association of radiotherapy with risk of second cancers and to assess the interaction of radiation treatment with age at diagnosis. All statistical tests were two-sided. Results Among 104760 one-year survivors of cervical cancer, the risk of all second cancers taken together was increased to a statistically significant extent (n = 12 496; SIR = 1.30; 95% confidence interval [Cl] = 1.28 to 1.33). Compared with the general population, in both radiotherapy (N = 52 613) and no-radiotherapy groups (N = 27382), risks for HPV-related cancers (of the pharynx, genital sites, and rectum/anus) and smoking-related cancers (of the pharynx, trachea/bronchus/lung, pancreas, and urinary bladder) were elevated to a statistically significant extent. Cervical cancer patients treated with radiotherapy, but not those who did not receive radiotherapy, were at increased risk for all second cancers and cancers at heavily irradiated sites (colon, rectum/anus, urinary bladder, ovary, and genital sites) beyond 40 years of follow-up compared with women in the general population. The association of radiotherapy with second cancer risk was modified by age at cervical cancer diagnosis for rectum/anus, genital sites, and urinary bladder, with higher hazard ratios for second cancer at younger ages of cervical cancer. After adjustment for competing mortality, the 40-year cumulative risk of any second cancer was higher among women diagnosed with cervical cancer before age 50 (22.2%; 95% Cl = 21.5% to 22.8%) than among women diagnosed after age 50 (16.4%; 95% Cl = 16.1% to 16.9%). Conclusion Cervical cancer patients treated with radiotherapy are at increased risk of second cancers at sites in close proximity to the cervix beyond 40 years of follow-up. C1 NIH, NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Iowa, Iowa City, IA USA. Danish Canc Soc, Copenhagen, Denmark. Karolinska Inst, Stockholm, Sweden. Canc Registry Norway, Oslo, Norway. Finnish Canc Registry, FIN-00170 Helsinki, Finland. Univ Helsinki, Cent Hosp, Helsinki, Finland. Int Epidemiol Inst, Rockville, MD USA. Exponent Inc, New York, NY USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RP Chaturvedi, AK (reprint author), NIH, NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7072, Rockville, MD 20852 USA. EM chaturva@mail.nih.gov RI Chaturvedi, Anil/J-2024-2015; OI Chaturvedi, Anil/0000-0003-2696-8899; Storm, Hans/0000-0001-7223-8198; Kleinerman, Ruth/0000-0001-7415-2478; Joensuu, Heikki/0000-0003-0281-2507 FU Intramural NIH HHS NR 33 TC 134 Z9 139 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 7 PY 2007 VL 99 IS 21 BP 1634 EP 1643 DI 10.1093/jnci/djm201 PG 10 WC Oncology SC Oncology GA 233DY UT WOS:000251071800015 PM 17971527 ER PT J AU Bergmann-Leitner, ES Duncan, EH Leitner, WW Neutzner, A Savranskaya, T Angov, E Tsokos, GC AF Bergmann-Leitner, Elke S. Duncan, Elizabeth H. Leitner, Wolfgang W. Neutzner, Albert Savranskaya, Tatyana Angov, Evelina Tsokos, George C. TI C3d-defined complement receptor-binding peptide p28 conjugated to circumsporozoite protein provides protection against Plasmodium berghei SO VACCINE LA English DT Article DE molecular adjuvant; DNA vaccines; complement C3d ID MOLECULAR ADJUVANT; IMMUNE-RESPONSES; MALARIA; C3D AB Immune response against circumsporozoite protein (CSP) of Plasmodium berghei, a major surface protein on the sporozoite, confers protection in various murine malaria models. Engineered DNA vaccine encoding CSP and 3 copies of C3d caused an unexpected loss in protection attributed to the binding of C3d to the C-terminal region of CSP. Because the C3d region known as p28 represents the complement receptor (CR) 2-binding motif, we developed a CSP-3 copies of p28 DNA construct (CSP-3p28). CSP-3p28-immunized mice were better protected against P.berghei sporozoites than CSP-immunized mice 6 weeks after the 2nd boost, produced sufficient IgGl anti-CSP and CSP C-terminus antibody and failed to produce IgG2a. CSP-3C3d-immunized mice were not protected, failed to produce IgG l and produced high amounts of IgG2a. We conclude that use of the CR2-binding motif of C3d as molecular adjuvant to CSP results in anti-malaria protective immune response probably by targeting the chimeric protein to CR2. Published by Elsevier Ltd. C1 Walter Reed Army Inst Res, Div Malaria Vaccine Dev, Silver Spring, MD 20910 USA. NIH, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20852 USA. Walter Reed Army Inst Res, Div Entomol, Silver Spring, MD 20910 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Rheumatol, Boston, MA 02115 USA. RP Bergmann-Leitner, ES (reprint author), Walter Reed Army Inst Res, Div Malaria Vaccine Dev, 503 Robert Grant Ave,Room 3W65, Silver Spring, MD 20910 USA. EM elke.bergmannleitner@us.army.mil RI Bergmann-Leitner, Elke/B-3548-2011; Leitner, Wolfgang/F-5741-2011; OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Leitner, Wolfgang/0000-0003-3125-5922; Neutzner, Albert/0000-0001-9254-5558 FU NIAID NIH HHS [R03 AI053463] NR 7 TC 17 Z9 20 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 7 PY 2007 VL 25 IS 45 BP 7732 EP 7736 DI 10.1016/j.vaccine.2007.08.030 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 233PU UT WOS:000251103600004 PM 17931754 ER PT J AU Eller, MA Eller, LA Opollo, MS Ouma, BJ Oballah, PO Galley, L Karnasuta, C Kim, SR Robb, ML Michael, NL Kibuuka, H Wabwire-Mangen, F Graham, BS Birx, DL de Souza, MS Cox, JH AF Eller, Michael A. Eller, Leigh Anne Opollo, Marc S. Ouma, Benson J. Oballah, Peter O. Galley, Lynee Karnasuta, Chitraporn Kim, Silvia Ratto Robb, Merlin L. Michael, Nelson L. Kibuuka, Hannah Wabwire-Mangen, Fred Graham, Barney S. Birx, Deborah L. de Souza, Mark S. Cox, Josephine H. TI Induction of HIV-specific functional immune responses by a multiclade HIV-1 DNA vaccine candidate in healthy Ugandans SO VACCINE LA English DT Article DE DNA vaccine; HIV-1; CTL; LPA; ADCC ID T-CELL RESPONSES; IMMUNOGENICITY EVALUATION; CLINICAL-TRIALS; PHASE-1 SAFETY; SUBTYPE-B; VOLUNTEERS; DIVERSITY; VECTOR; ADULTS AB A phase I randomized, double blind, placebo-controlled trial to assess the immunogenicity of a multiclade HIV-1 DNA plasmid vaccine was conducted in 31 HIV-1-negative Ugandans. Following immunization with DNA at 0, 1, and 2 months, the frequency of HIV-specific immune responses was assessed up to 10 months using a standard chromium release assay (CRA), lymphoproliferative assay (LPA), and antibody dependent cell-mediated cytotoxicity assay (ADCC). Seven of 15 (47%) vaccinees demonstrated CTL activity using the CRA to HIV-1 Env B with responses observed 1 month following the second vaccination and as late as 7 months following complete immunization. Additionally, lymphoproliferative reponses were observed in 14/15 vaccinees against p24. No CTL or LPA responses were observed at baseline or in the placebo group. ADCC activity was minimally induced by DNA vaccination. This study demonstrates that immunization with DNA alone induces CTL and lymphoproliferative responses in a population that will participate in a phase IIb study evaluating HIV-1 DNA priming followed by boosting with a replication-defective recombinant adenovirus vector. (c) 2007 Elsevier Ltd. All rights reserved. C1 Makerere Univ, Walter Reed Project, Kampala, Uganda. Henry M Jackson Fdn, Rockville, MD USA. Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD USA. NIH, Vaccine Res, Bethesda, MD 20892 USA. Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Eller, MA (reprint author), Makerere Univ, Walter Reed Project, Kampala, Uganda. EM meller@muwrp.org OI waluyo, imam/0000-0002-1813-9487 NR 18 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 7 PY 2007 VL 25 IS 45 BP 7737 EP 7742 DI 10.1016/j.vaccine.2007.08.056 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 233PU UT WOS:000251103600005 PM 17920731 ER PT J AU Yamaguchi, H Durell, SR Chatterjee, DK Anderson, CW Appella, E AF Yamaguchi, Hiroshi Durell, Stewart R. Chatterjee, Deb K. Anderson, Carl W. Appella, Ettore TI The wip1 phosphatase PPM1D dephosphorylates SQ/TQ motifs in checkpoint substrates phosphorylated by PI3K-like kinases SO BIOCHEMISTRY LA English DT Article ID PROTEIN PHOSPHATASES; SIGNALING PATHWAYS; DNA-DAMAGE; ATM; AMPLIFICATION; P38; P53; ACTIVATION; INHIBITOR; RADIATION AB The wild-type p53-induced phosphatase Wip1 (PP2C delta or PPM1D) is a member of the protein phosphatase 2C (PP2C) family and controls cell cycle checkpoints in response to DNA damage. p38 MAPK and ATM were identified as physiological substrates of Wip1, and we previously reported a substrate motif that was defined using variants of the p38(180pT 182pY) diphosphorylated peptide, TDDEMpTGpYVAT. However, the substrate recognition motifs for Wip1 have not been fully defined as the sequences surrounding, the targeted residues in ATM and p38 MAPK appear to be unrelated. Using a recombinant human Wip1 catalytic domain (rWip1), in this study we measured the kinetic parameters for variants of the ATM(1981pS) phosphopeptide, AFEEGpSQSTTI. We found that rWip1 dephosphorylates phosphoserine and phosphothreonine in the p(SIT)Q motif, which is an essential requirement for substrate recognition. In addition, acidic, hydrophobic, or aromatic amino acids surrounding the p(S/T)Q sequence have a positive influence, while basic amino acids have a negative influence on substrate dephosphorylation. The kinetic constants allow discrimination between true substrates and nonsubstrates of Wip1, and we identified several new putative substrates that include HDM2, SMC1A, ATR, and Wip1 itself. A three-dimensional molecular model of Wip1 with a bound substrate peptide and site-directed mutagenesis analyses suggested that the important residues for ATM(1981 pS) substrate recognition are similar but not identical to those for the p38(180pT 182pY) substrate. Results from this study should be useful for predicting new physiological substrates that may be regulated by Wip1 and for developing selective anticancer drugs. C1 NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. SAIC Frederick Inc, NCI, Peotein Express Lab, Ft Detrick, MD 21702 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Appella, E (reprint author), NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. EM appellae@pop.nci.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 35 TC 34 Z9 35 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 6 PY 2007 VL 46 IS 44 BP 12594 EP 12603 DI 10.1021/bi701096s PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226FA UT WOS:000250571800010 PM 17939684 ER PT J AU Thorp, E Kuriakose, G Shah, YM Gonzalez, FJ Tabas, I AF Thorp, Edward Kuriakose, George Shah, Yatrik M. Gonzalez, Frank J. Tabas, Ira TI Pioglitazone increases macrophage apoptosis and plaque necrosis in advanced atherosclerotic lesions of nondiabetic low-density lipoprotein receptor-null mice SO CIRCULATION LA English DT Article DE apoptosis; atherosclerosis; macrophages; plaque; drugs ID TYPE-2 DIABETES-MELLITUS; NF-KAPPA-B; PPAR-GAMMA; INFLAMMATORY RESPONSE; INSULIN-RESISTANCE; ALPHA; TROGLITAZONE; PATHWAY; CONSEQUENCES; ACTIVATION AB Background - Thiazolidinediones (TZDs), which have actions that involve both peroxisome proliferator - activated receptor ( PPAR)-gamma-dependent and -independent effects, improve insulin sensitivity in type II diabetes and inhibit early atherogenesis in mice. However, the effects of TZDs on advanced lesion progression are unknown. Methods and Results - Pioglitazone and rosiglitazone enhanced macrophage apoptosis by a number of stimuli, including those thought to be important in advanced atherosclerosis. Macrophage death was not enhanced by non-TZD PPAR gamma activators, and TZD-induced apoptosis was still observed in PPAR gamma-deficient macrophages. In wild-type macrophages, death enhancement was associated with reduced activation of the cell-survival mediator nuclear factor-kappa B. TZDs also increased the ability of macrophages to phagocytically clear apoptotic cells, which is proposed to protect against plaque necrosis in advanced lesions. The mechanism of this effect was complex, involving both PPAR gamma-dependent and - independent mechanisms. To explore the net effect on advanced atherosclerosis in vivo, Ldlr(-/-) mice were fed a nondiabetogenic cholesterol-enriched diet to promote midstage lesions. Then, pioglitazone was administered with the diet for an additional 10 weeks. Aortic root lesions from the pioglitazone-treated mice showed a substantial increase in apoptotic cells and plaque necrosis compared with lesions from non - drug-treated mice. Conclusions - The potential atheroprotective effects of TZDs conferred by insulin sensitization may be partially offset by adverse effects on advanced atherosclerosis. Because the mechanisms of the beneficial and proposed adverse effects may differ, these findings have potentially important implications for drug optimization. C1 Columbia Univ, Dept Med, New York, NY 10032 USA. Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY USA. Natl Canc Inst, Natl Inst Hlth, Canc Res Ctr, Lab Metab, Bethesda, MD USA. RP Tabas, I (reprint author), Columbia Univ, Dept Med, 630 W 168th St, New York, NY 10032 USA. EM iat1@columbia.edu OI Thorp, Edward/0000-0003-1387-7058 FU NHLBI NIH HHS [HL54591, HL75662] NR 35 TC 42 Z9 44 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 6 PY 2007 VL 116 IS 19 BP 2182 EP 2190 DI 10.1161/CIRCULATIONAHA.107.698852 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 228CN UT WOS:000250704800012 PM 17967777 ER PT J AU Perez, MA Tanaka, S Wise, SP Sadato, N Tanabe, HC Willingham, DT Cohen, LG AF Perez, M. A. Tanaka, S. Wise, S. P. Sadato, N. Tanabe, H. C. Willingham, D. T. Cohen, L. G. TI Neural substrates of intermanual transfer of a newly acquired motor skill SO CURRENT BIOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; MACAQUE MONKEY; SUPPLEMENTARY; CEREBELLAR; CORTEX; AREAS; ORGANIZATION; PLASTICITY; SEQUENCES; THALAMUS AB In healthy humans, the two cerebral hemispheres show functional specialization to a degree unmatched in other animals, and such strong hemispheric specialization contributes to unimanual skill acquisition [1, 2]. When most humans learn a new motor skill with one hand, this process results in performance improvements in the opposite hand as well [3-6]. Despite the obvious adaptive advantage of such intermanual transfer, there is no direct evidence identifying the neural substrates of this form of skill acquisition [7-9]. Here, we used functional magnetic resonance imaging (fMRI) to study brain regions activated during intermanual transfer of a learned sequence of finger movements. First, we found that the supplementary motor area (SMA) has more activity when a skill has transferred well than when it has transferred poorly. Second, we found that fMRI activity in the ventrolateral posterior thalamic nucleus correlated with successful future intermanual transfer, whereas activity in the ventrolateral anterior thalamic nucleus correlated with past intermanual transfer. Third, we found that repetitive transcranial magnetic stimulation applied over the SMA blocked intermanual transfer without affecting skill acquisition. These findings provide direct evidence for an SMA-based mechanism that supports intermanual transfer of motor-skill learning. C1 NINDS, Human Cort Physiol Sect & Stroke, Neurorehabil Clin, NIH, Bethesda, MD 20892 USA. NIMH, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. Natl Inst Physiol Sci, Div Cerebral Integrat, Okazaki, Aichi 4448585, Japan. Univ Virginia, Dept Psychol, Charlottesville, VA 22904 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect & Stroke, Neurorehabil Clin, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM cohenl@ninds.nih.gov FU Intramural NIH HHS NR 34 TC 60 Z9 61 U1 0 U2 9 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 NOV 6 PY 2007 VL 17 IS 21 BP 1896 EP 1902 DI 10.1016/j.cub.2007.09.058 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 228YP UT WOS:000250768800029 PM 17964167 ER PT J AU Kim, ESH Ishwaran, H Blackstone, E Lauer, MS AF Kim, Esther S. H. Ishwaran, Hemant Blackstone, Eugene Lauer, Michael S. TI External prognostic validations and comparisons of age- and gender-adjusted exercise capacity predictions SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HEART-RATE RECOVERY; TREADMILL EXERCISE; CARDIORESPIRATORY FITNESS; METABOLIC EQUIVALENTS; ASYMPTOMATIC WOMEN; PHYSICAL-FITNESS; HEALTHY-MEN; FOLLOW-UP; MORTALITY; DEATH AB Objectives The purpose of this study was to externally validate the prognostic value of age- and gender-based nomograms and categorical definitions of impaired exercise capacity (EC). Background Exercise capacity predicts death, but its use in routine clinical practice is hampered by its close correlation with age and gender. Methods For a median of 5 years, we followed 22,275 patients without known heart disease who underwent symptom-limited stress testing. Models for predicted or impaired EC were identified by literature search. Gender-specific multivariable proportional hazards models were constructed. Four methods were used to assess validity: Akaike Information Criterion (AIC), right-censored c-index in 100 out-of-bootstrap samples, the Nagelkerke Index R-2, and calculation of calibration error in 100 bootstrap samples. Results There were 646 and 430 deaths in 13,098 men and 9,177 women, respectively. Of the 7 models tested in men, a model based on a Veterans Affairs cohort (predicted metabolic equivalents [METs] = 18 - [0.15 X age]) had the highest AIC and R2. In women, a model based on the St. James Take Heart Project (predicted METs = 14.7 - [0.13 x age]) performed best. Categorical definitions of fitness performed less well. Even after accounting for age and gender, there was still an important interaction with age, whereby predicted EC was a weaker predictor in older subjects (p for interaction < 0.001 in men and 0.003 in women). Conclusions Several methods describe EC accounting for age and gender-related differences, but their ability to predict mortality differ. Simple cutoff values fail to fully describe EC's strong predictive value. C1 Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. Cleveland Clin, Dept Cardiothorac Surg, Cleveland, OH 44106 USA. NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), 6701 Rockledge Dr,Room 10122, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 FU NHLBI NIH HHS [R01 HL-072771-02, P50 HL-77107, R01 HL-66004-2]; NICHD NIH HHS [K12 HD049091] NR 31 TC 33 Z9 33 U1 2 U2 4 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 NOV 6 PY 2007 VL 50 IS 19 BP 1867 EP 1875 DI 10.1016/j.jacc.2007.08.003 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 229FK UT WOS:000250788300009 PM 17980254 ER PT J AU Pabst, G Danner, S Podgornik, R Katsaras, J AF Pabst, Georg Danner, Sabine Podgornik, Rudi Katsaras, John TI Entropy-driven softening of fluid lipid Bilayers by alamethicin SO LANGMUIR LA English DT Article ID MEMBRANE-INDUCED INTERACTIONS; X-RAY-SCATTERING; ANTIMICROBIAL PEPTIDES; PHOSPHOLIPID-BILAYERS; PORE FORMATION; PHOSPHATIDYLCHOLINE BILAYERS; BENDING RIGIDITY; MODEL MEMBRANES; FULL HYDRATION; PERTURBATION AB Using dilatometry and small-angle X-ray diffraction, we have studied under bulk conditions the structural changes and elastic response of dioleoyl phosphatidylcholine bilayers to alamethicin. With increasing peptide concentration, we found a progressive thinning of the membrane. However, in contrast to previously published reports, this thinning exhibits exponential behavior. Furthermore, an increase in alamethicin content resulted in an increased lateral area per lipid and a swelling of the multibilayers which can be attributed to a decrease in the bilayer's bending rigidity by similar to 50%. At the same time, hydration and van der Waals forces remained unaffected by the presence of the peptide. Interestingly, all elastic and structural parameters followed the same exponential form found for the membrane thickness, implying a common underlying mechanism for all of these structural parameters. Our results can be understood by introducing an additional entropy term into the free-energy description of peptide incorporation, a term previously not considered. As a result, we have been able to reconcile recent controversies regarding the effect of peptides on membrane thinning. C1 Austrian Acad Sci, Inst Biophys & Nanosyst Res, A-8042 Graz, Austria. NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Univ Ljubljana, Fac Math & Phys, Ljubljana 1000, Slovenia. Jozef Stefan Inst, Dept Theoret Phys, Ljubljana 1000, Slovenia. CNR, Canadian Neutron Beam Ctr, Chalk River, ON K07 1J0, Canada. Brock Univ, Dept Phys, St Catharines, ON L2S 3A1, Canada. Univ Guelph, Guelph Waterloo Phys Inst, Dept Phys, Guelph, ON N1G 2W1, Canada. Univ Guelph, Biophys Interdept Grp, Guelph, ON N1G 2W1, Canada. RP Pabst, G (reprint author), Austrian Acad Sci, Inst Biophys & Nanosyst Res, Schmiedlstr 6, A-8042 Graz, Austria. EM georg.pabst@oeaw.ac.at RI Podgornik, Rudolf/C-6209-2008; Pabst, Georg/I-6919-2015; OI Podgornik, Rudolf/0000-0002-3855-4637; Pabst, Georg/0000-0003-1967-1536; Katsaras, John/0000-0002-8937-4177 NR 70 TC 37 Z9 37 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD NOV 6 PY 2007 VL 23 IS 23 BP 11705 EP 11711 DI 10.1021/la701586c PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 226JE UT WOS:000250584500058 PM 17939689 ER PT J AU Veatch, SL Soubias, O Keller, SL Gawrisch, K AF Veatch, Sarah L. Soubias, Olivier Keller, Sarah L. Gawrisch, Klaus TI Critical fluctuations in domain-forming lipid mixtures SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lipid rafts; liquid-immiscibility; NMR relaxation; phase diagram; critical behavior ID NUCLEAR-MAGNETIC-RESONANCE; DIFFERENTIAL SCANNING CALORIMETRY; DIPALMITOYLPHOSPHATIDYLCHOLINE BILAYERS; CHOLESTEROL INTERACTIONS; FLUORESCENCE MICROSCOPY; PHASE-EQUILIBRIA; TERNARY MIXTURES; MODEL MEMBRANES; LIQUID-PHASES; NMR-SPECTRA AB Critical fluctuations are investigated in lipid membranes near miscibility critical points in bilayers composed of dioleoylphosphatidylcholine, chain perdeuterated dipalmitoyl phosphatidylcholine, and cholesterol. Phase boundaries are mapped over the temperature range from 10 degrees C to 60 degrees C by deuterium NMR. Tie-lines and three-phase triangles are evaluated across two-phase and three-phase regions, respectively. In addition, a line of miscibility critical points is identified. NMR resonances are broadened in the vicinity of critical points, and broadening is attributed to increased transverse relaxation rates arising from modulation of chain order with correlation times on a microsecond time scale. We conclude that spectral broadening arises from composition fluctuations in the membrane plane with dimensions of < 50 nm and speculate that similar fluctuations are commonly found in cholesterol-containing membranes. C1 NIAAA, NIH, Bethesda, MD 20892 USA. Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z4, Canada. Univ Washington, Dept Chem, Seattle, WA 98195 USA. Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA. RP Gawrisch, K (reprint author), NIAAA, NIH, Bethesda, MD 20892 USA. EM gawrisch@helix.nih.gov RI Wunder, Stephanie/B-5066-2012; Zdilla, Michael/B-4145-2011; Veatch, Sarah/G-9512-2016 OI Veatch, Sarah/0000-0002-9317-2308 FU Intramural NIH HHS NR 40 TC 214 Z9 215 U1 7 U2 90 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 NOV 6 PY 2007 VL 104 IS 45 BP 17650 EP 17655 DI 10.1073/pnas.0703513104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 230TA UT WOS:000250897600021 PM 17962417 ER PT J AU Cheng, Y Nash, HA AF Cheng, Yuzhong Nash, Howard A. TI Drosophila TRP channels require a protein with a distinctive motif encoded by the inaF locus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE accessory protein; complex formation; ion channel; transmembrane interaction ID TERMINATION AB In both vertebrates and invertebrates, ion channels of the TRP superfamily are known to be influenced by a variety of accessory factors, but the list of interacting proteins is acknowledged to be incomplete. Although previous work showed that Drosophila TRP function is disrupted by mutations in the inaF locus, the mechanism of this effect has remained obscure. Here we show that a previously overlooked small protein, INAF-B, is encoded by the locus and fulfills its critical role in retinal physiology. The 81-aa INAF-B gene product is an integral membrane protein that colocalizes to rhab-domeres along with TRIP channels. Immumoprecipitation experiments demonstrate that the two proteins participate in a complex, and blotting experiments show that neither protein survives in the absence of the other. Both proteins are normally part of a large supramolecular assembly, the signalplex, but their interaction persists even in the absence of the scaffold for this structure. The inaF locus encodes three other proteins, each of which has diverged from INAF-B except for a 32-aa block of residues that encompasses a transmembrane domain. This conserved sequence defines an inaF motif, representatives of which are found in proteins from organisms as diverse as nematodes, fish, and humans. Given the role of INAF-B, these proteins are good candidates for interacting partners of other members of the TRIP superfamily. C1 NIMH, NIH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Nash, HA (reprint author), NIMH, NIH, Mol Biol Lab, Bldg 35,Room 18-1002,9000 Rockville Pike, Bethesda, MD 20892 USA. EM howardnash@mail.nih.gov FU Intramural NIH HHS NR 22 TC 12 Z9 12 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 6 PY 2007 VL 104 IS 45 BP 17730 EP 17734 DI 10.1073/pnas.0708368104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 230TA UT WOS:000250897600035 PM 17968007 ER PT J AU Gaur, D Singh, S Singh, S Jiang, L Diouf, A Miller, LH AF Gaur, Deepak Singh, Sanjay Singh, Subhash Jiang, Lubin Diouf, Ababacar Miller, Louis H. TI Recombinant Plasmodium falciparum reticulocyte homology protein 4 binds to erythrocytes and blocks invasion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE erythrocyte invasion; red cell invasion; invasion pathways; erythrocyte binding; sialic acids ID BLOOD-GROUP DETERMINANTS; MONOCLONAL-ANTIBODIES; MALARIA PARASITES; KNOWLESI MALARIA; RECEPTOR; VIVAX; MEROZOITES; LIGAND; MECHANISM; ANTIGENS AB Plasmodium falciparum invasion of human erythrocytes involves several parasite and erythrocyte receptors that enable parasite invasion by multiple redundant pathways. A key challenge to the development of effective vaccines that block parasite infection of erythrocytes is identifying the players in these pathways and determining their function. Invasion by the parasite clone, Dd2, requires sialic acid on the erythrocyte surface; Dd2/NM is a variant selected for its ability to invade neuraminidase-treated erythrocytes that lack sialic acid. The P. falciparum protein, reticulocyte homology 4 (PfRH4), is uniquely up-regulated in Dd2/NM compared with Dd2, suggesting that it may be a parasite receptor involved in invasion. The aim of the present study was to determine the role of PfRH4 in invasion of erythrocytes and to determine whether it is a target of antibody-mediated blockade and thus a vaccine candidate. We show that both native PfRH4 and a recombinant 30-kDa protein to a conserved region of PfRH4 (rRH4(30)) bind strongly to neuraminiclase-treated erythrocytes. rRH4(30) blocks both the erythrocyte binding of the native PfRH4 and invasion of neuraminidase-treated erythrocytes by Dd2/NM. Taken together, these results indicate that PfRH4 is a parasite receptor involved in sialic acid-independent invasion of erythrocytes. Although antibodies to rRH4(30) block binding of the native protein to erythrocytes, these antibodies failed to block invasion. These findings suggest that, although PfRH4 is required for invasion of neuraminiclase-treated erythrocytes by Dd2/NM, it is inaccessible for antibody-mediated inhibition of the invasion process. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. RP Gaur, D (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Twinbrook 3,12735 Twinbrook Parkway, Bethesda, MD 20892 USA. EM dgaur@niaid.nih.gov; lmiller@niaid.nih.gov FU Intramural NIH HHS NR 29 TC 69 Z9 70 U1 1 U2 1 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 NOV 6 PY 2007 VL 104 IS 45 BP 17789 EP 17794 DI 10.1073/pnas.0708772104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 230TA UT WOS:000250897600045 PM 17971435 ER PT J AU Bell, DR Clode, S Fan, MQ Fernandes, A Foster, PMD Jiang, T Loizou, G MacNicoll, A Miller, B Rose, M Tran, L White, S AF Bell, David R. Clode, Sally Fan, Ming Qi Fernandes, Alwyn Foster, Paul M. D. Jiang, Tao Loizou, George MacNicoll, Alan Miller, Brian Rose, Martin Tran, Lang White, Shaun TI TCDD is a potent developmental toxin, but fails to affect spermatogenesis in offspring of chronically treated CRL : WI(Han) rats SO TOXICOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Toxicological-Society CY APR 15-18, 2007 CL Univ Surrey, Guildford, ENGLAND SP British Toxicol Soc HO Univ Surrey C1 Univ Nottingham, Sch Biol, Nottingham NG7 2RD, England. Covance Labs Ltd, Harrogate, England. Cent Sci Lab, Environm Contaminants & Trace Element Studies FSQ, York YO41 1LZ, N Yorkshire, England. NIEHS, Res Triangle Pk, NC 27709 USA. Hlth & Safety Lab, Buxton SK17 9JN, England. Inst Occupat Med, Edinburgh EH14 4AP, Midlothian, Scotland. EM david.bell@nottingham.ac.uk OI Rose, Martin/0000-0001-7071-180X NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD NOV 6 PY 2007 VL 240 IS 3 SI SI BP 170 EP 170 DI 10.1016/j.tox.2007.06.049 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 233QK UT WOS:000251105200056 ER PT J AU Alves, G Ogurtsov, AY Wu, WW Wang, G Shen, RF Yu, YK AF Alves, Gelio Ogurtsov, Aleksey Y. Wu, Wells W. Wang, Guanghui Shen, Rong-Fong Yu, Yi-Kuo TI Calibrating e-values for MS(2) database search methods SO BIOLOGY DIRECT LA English DT Article ID TANDEM MASS-SPECTROMETRY; PROTEIN IDENTIFICATION DATA; SEQUENCE DATABASES; SPECTRAL DATA; LABEL-FREE; PEPTIDES; QUANTIFICATION; GUIDELINES; ALGORITHM AB Background: The key to mass-spectrometry-based proteomics is peptide identification, which relies on software analysis of tandem mass spectra. Although each search engine has its strength, combining the strengths of various search engines is not yet realizable largely due to the lack of a unified statistical framework that is applicable to any method. Results: We have developed a universal scheme for statistical calibration of peptide identifications. The protocol can be used for both de novo approaches as well as database search methods. We demonstrate the protocol using only the database search methods. Among seven methods-SEQUEST (v27 rev12), ProbID (v1.0), InsPecT (v20060505), Mascot (v2.1), X!Tandem (v1.0), OMSSA (v2.0) and RAId_DbS-calibrated, except for X! Tandem and RAId_DbS most methods require a rescaling according to the database size searched. We demonstrate that our calibration protocol indeed produces unified statistics both in terms of average number of false positives and in terms of the probability for a peptide hit to be a true positive. Although both the protocols for calibration and the statistics thus calibrated are universal, the calibration formulas obtained from one laboratory with data collected using either centroid or profile format may not be directly usable by the other laboratories. Thus each laboratory is encouraged to calibrate the search methods it intends to use. We also address the importance of using spectrum-specific statistics and possible improvement on the current calibration protocol. The spectra used for statistical (E-value) calibration are freely available upon request. Open peer review: Reviewed by Dongxiao Zhu (nominated by Arcady Mushegian), Alexey Nesvizhskii (nominated by King Jordan) and Vineet Bafna. For the full reviews, please go to the Reviewers' comments section. C1 [Alves, Gelio; Ogurtsov, Aleksey Y.; Yu, Yi-Kuo] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Wu, Wells W.; Wang, Guanghui] NHLBI, Proteom Core Facil, Bethesda, MD 20892 USA. RP Yu, YK (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM alves@ncbi.nlm.nih.gov; ogurtsov@ncbi.nlm.nih.gov; wuw2@nhlbi.nih.gov; wangg2@nhlbi.nih.gov; shenr@nhlbi.nih.gov; yyu@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 24 TC 12 Z9 12 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD NOV 5 PY 2007 VL 2 AR 26 DI 10.1186/1745-6150-2-26 PG 14 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 253OU UT WOS:000252528300001 PM 17983478 ER EF